Rheumatic and Systemic Disease Clinical Findings

Rheumatic and Systemic Disease
1. The following clinical picture depict a hereditary periodic fever syndrome:

 Urticarial papules and plaques on face, trunk and extremities lasting 1 to 2 days
 Myalgia
 Sensorineural hearing loss
 Amyloidosis in about 25% of cases
 Conjunctivitis
A. Familial Mediterranean fever
B. Hyperimmunoglobulinemia D with periodic fever syndrome
C. TNF receptor-associated periodic syndrome
D. Muckle–Wells syndrome
E. Neonatal-onset multisystem inflammatory disease
Correct answer: (D) Muckle–Wells syndrome.

Explanation: The following clinical picture depict a hereditary periodic fever syndrome called Muckle Wells syndrome:
- Urticarial papules and plaques on face, trunk and extremities lasting 1 to 2 days
- Myalgia
- Sensorineural hearing loss
- Amyloidosis in about 25% of cases
- Conjonctivitis
Neonatal-onset multisystem inflammatory disease has a similar clinical picture but the urticarial rash is continuous and
has flares. Familial Mediterranean fever presents with an erysipeloid erythema of the lower limbs with edema. Ocular
findings are uncommon. Amyloidosis is most common in M694V homozygotes. No hearing loss is associated but aseptic
meningitis is possible but rarely occurs. Hyperimmunoglobulinemia D with periodic fever syndrome presents with
erythematous macules and edematous papules, which may become purpuric; occasional oral and vaginal ulcers. Their
distribution is similar to Muckle-Wells syndrome, on the face, trunk and extremities. Ocular findings are uncommon. No
hearing loss is associated but headaches can be a part of the syndrome. TNF receptor-associated periodic syndrome
presents with erythematous patches and edematous plaques that are often annular or serpiginous. They are ecchymotic
in appearance. They migrate distally on an extremity with underlying myalgia but may be more widespread. Periorbital
edema, conjunctivitis and rarely uveitis are found. No hearing loss is associated but headaches are possible.
2. Which of the following autoantibodies are both diagnostic and can be used to monitor disease severity?
A. Anti-dsDNA (double stranded DNA)
B. Cytoplasmic antineutrophil cytoplasmic antibodies
C. Anti-RNAP (RNA polymerase)
D. Choices A and C only
E. All of the above can be diagnostic and used to monitor disease severity
Correct answer: (E) All of the above can be diagnostic and used to monitor disease severity.
Explanation: Antibodies directed to all of the choices (A, B, and C) can be used to monitor disease severity as well as play
a principle in laboratory aided clinical correlation that can lead to a diagnosis of the autoimmune disease they are
associated with.
(A) Systemic lupus disease activity correlates with elevated levels of anti-dsDNA antibodies, with a greater correlation
associated in combination with falling complement levels. High levels of anti-dsDNA levels also correspond to increased
risk for nephritis associated with lupus erythematosus.
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(B) C-ANCA or cytoplasmic antineutrophil cytoplasmic antibodies, can be used to diagnose and monitor disease severity
in Wegeners granulomatosis.
(C) Anti-RNAP or RNA polymerase antibodies are both diagnostic for scleroderma, and also serve as a marker for disease
progression towards renal crisis.
3. What patients have the highest incidence of SCC?

A. Heart transplant patients
B. Liver transplant patients
C. Renal transplant patients
D. Lung transplant patients
Correct answer: (A) Heart transplant patients.

Explanation: After adjustment for age and type of immunosuppressive regimen, heart transplant recipients had a
significantly (2.9 times) higher risk than kidney transplant recipients.
(B) Liver transplant patients do not have the highest incidence of SCC.
(C) After adjustment for age, kidney transplant recipients receiving cyclosporine, azathioprine, and prednisolone had a
significantly (2.8 times) higher risk of cutaneous SCC relative to those receiving azathioprine and prednisolone. However,
heart transplant patients have been shown to have the highest incidence of SCC.
(D) Lung transplant patients do not have the highest incidence of SCC.
4. Which of the following conditions is associated with IgG and IgA along the basement membrane and hair follicles?
A. HSP
B. Linear IgA
C. Lupus
D. DH
Correct answer: (C) Lupus.

Explanation: Lupus is associated with granular deposition of IgG, IgM and IgA at the basement membrane (the ‘lupus
band’), along with perifollicular immune deposits.
(A) HSP is associated with perivascular IgA.
(B) Linear IgA is associated with IgA (and sometimes IgG) deposition along the BMZ.
(D) DH is associated with granular IgA deposition along the dermal papillae.
5. Which of the following findings of Sjögren’s Syndrome is related to an increased mortality rate and an increased risk
of developing B-cell lymphomas?
A. Cutaneous small vessel vasculitis
B. Cryoglobulinemia
C. Hypocomplementemia
D. Choices B and C only
E. All of the above
Correct answer: (E) All of the above.

Explanation: Cutaneous small vessel vasculitis in association with Sjögren’s Syndrome is the cutaneous finding most
highly correlated with increased mortality. However, patients with either cutaneous small vessel vasculitis, which may
present as palpable purpura or urticaria, cryoglobulinemia, and/or hypocomplementemia, all carry an increase risk of
mortality as well as an increased risk of developing B-cell lymphomas. If these cutaneous features are present, there is an
increased risk for developing B-cell lymphomas and a 16-fold greater risk of developing extra-nodal lymphoma
(MALToma’s) in patients with SjS when compared to the general population.
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6. All of the following characteristics of dermatomyositis are true EXCEPT?
A. A diagnosis of dermatomyositis requires demonstration of inflammation of skeletal muscle
B. Dermatomyositis occurs in a bimodal age distribution
C. Children with dermatomyositis are at increased risk cutaneous calcinosis
D. Adults with dermatomyositis are at increased risk of internal malignancy
E. All of the above statements are correct
Correct answer: (A) A diagnosis of dermatomyositis requires demonstration of inflammation of skeletal muscle.
Explanation: All of the above choices (B-E) are true except choice A. The diagnosis of dermatomyositis (DM) does not
require the presence of demonstrable inflammation of skeletal muscle. A variant of dermatomyositis without objective
evidence of skeletal muscle inflammation, called amyopathic dermatomyositis, represents an often-misdiagnosed
variant of adult-onset DM with similar prognostic outcomes and risks of malignancy seen in those patients with classic
adult-onset DM. Dermatomyositis does have a bimodal age distribution with a higher risk of cutaneous calcinosis in
pediatric patients with DM, and internal malignancy in adult-onset DM.
7. All of the following pathologic features aid in distinguishing rheumatoid nodules from granuloma annulare EXCEPT?
A. Depth of the granuloma
B. Palisading of histiocytes
C. The presence of extensive fibrosis
D. Comparatively less mucin
E. All of the above distinguish a rheumatoid nodule from granuloma annulare
Correct answer: (B) Palisading of histiocytes.

Explanation: Palisading of histiocytes around necrobiotic collagen is a feature seen in both granuloma annulare and
rheumatoid nodules on histopathology, making the initial diagnosis less distinctive.
(A) Rheumatoid nodules tend to be deeper in the dermis, even extending into the sub cutis, while classic granuloma
annulare remains closer to the epidermis and occupies most frequently the superficial dermis. However, subcutaneous
granuloma annulare can present in the mid- to deep dermis and additional factors are required to distinguish this subset
of granuloma annulare from rheumatoid nodules.
(C) (D) Extensive fibrosis, giving the granulomas of rheumatoid nodules a more well-defined and sharply marginated
appearance, as well as the diminished amount of mucin when compared to granuloma annulare, are additional
histopathologic features that aid in distinguishing the two diagnoses.
8. Scurvy, although less common than in earlier times, is still encountered in particular settings such as a vitamin C
poor diet, vagrancy or restrictive diets. Which of the following hair findings is most likely to be found?
A. Miniaturized hair
B. Corkscrew hair
C. Trichorrhexis invaginata
D. Bubble hair
E. Trichoschisis
Correct answer: (B) Corkscrew hair.

Explanation: Scurvy is the result of a vitamin C deficiency. Perifollicular purpura and corkscrew hairs are found. It’s
pathophysiology involves the collagen degeneration in the vasculature due to vitamin C deficiency. Anemia is the result
of gastrointestinal blood loss. Gingivitis with friable gums and easy bleeding, conjunctival hemorrhage, difficulty walking
are also found. The treatment is simple as it requires only vitamin C replacement. Miniaturized hair is found in
androgenetic alopecia and caused by sexual hormone sensitive hair. Trichorrhexis invaginata (or bamboo hair) is a
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feature of Netherton syndrome and caused by a mutation in SPINK5 encoding LETK1. Bubble hair is seen in young women
and is caused by traumatic hair care techniques involving heat, as from a malfunctioning hair dryer. The hair grows back
normally with gentle hair care and styling. Trichoschisis is the name given to hair fractures. They are found mainly in
trichothiodystrophy, a disease in which the hair is sulfur-deficient. Trichothiodystrophy is an autosomal-recessive
disorder. One phenotype of the disease is called PIBIDS and refers to the following characteristics: P (photosensitivity), I
(ichthyosis), B (brittle hair), I (intellectual impairment), D (decreased fertility) and S (short stature).
9. Systemic-onset juvenile idiopathic arthritis, or Still’s disease, is categorized as an autoinflammatory disease driven by
the abnormal production of the pro-inflammatory cytokine IL-1. Which of the following medications would have the
greatest effect on controlling this disease?
A. Etanercept
B. Rituximab
C. Infliximab
D. Anakinra
E. Adalimumab
Correct answer: (D) Anakinra.

Explanation: Anakinra is a synthetic medication that mimics the interleukin-1 receptor antagonist. It is often used in
diseases in which overproduction of IL-1 is responsible for several re-occurring signs and symptoms shared between
diseases with a similar underlying pathogenesis. These typically consist of periodic fevers, arthralgias that occur
simultaneously with periodic fevers, and the presence of skin lesions. The rash that presents in Still’s disease or systemic-
onset juvenile idiopathic arthritis (SoJIA) is characterized by an evanescent erythematous eruption that accompanies
spiking fevers. Anakinra’s effect serves to increase the antagonism of the IL-1 receptor decreasing the abnormal
overproduction of IL-1, thusly specifically targeting the dysregulated pro-inflammatory state. Both Etanercept (Choice A),
a soluble tumor necrosis alpha receptor (TNF-alpha), and Adalimumab (Choice E), a human-derived antibody to
circulating TNF-alpha, exert their anti-inflammatory effect on this specific cytokine only. While these unique biologic
immune-suppressants have an anti-inflammatory effect, their mechanism of action does not specifically target the
underlying pathogenesis of SoJIA. Similarly, Infliximab (C), a murine-human chimeric TNF-alpha antibody, does not
specifically target the overproduction of IL-1 in SoJIA. Rituximab (B), another chimeric monoclonal antibody, exerts its
antagonist effect on B-cells by binding to a homologous B-cell surface protein, CD20.
10. Which pair of autoantibodies is INCORRECTLY paired to the phenotypic variation of Dermatomyositis?
A. anti-p155 autoantibodies and increased risk of adenocarcinoma
B. anti-Mi2 autoantibodies and hyperkeratotic papules on the flexures of the digits with frayed cuticles
C. anti-Jo1 autoantibodies and Raynaud’s phenomenon with interstitial lung disease
D. anti-SRP autoantibodies and dermatomyositis with fulminant renal disease
E. anti-MDA5/CADM-140 autoantibodies and rapidly progressive interstitial lung disease
Correct answer: (D) anti-SRP autoantibodies and dermatomyositis with fulminant renal disease.
Explanation: The pair of anti-SRP and autoantibodies with fulminant renal disease is incorrect. Anti-SRP (signal
recognition particle) autoantibodies are associated with fulminant dermatomyositis with an increased mortality rate
secondary to cardiac involvement. (A) (B) (C) (E) These are all correct.
(A) In one study, 80% of adult patients with amyopathic (no skeletal muscle involvement) dermatomyositis,
demonstrated positive serology for anti-p155 autoantibodies. This same antibody was found in 20-30% of juvenile-onset
and classic adult-onset dermatomyositis. This protein is homologous to the transcriptional intermediary factor 1-gamma
and is associated with an increased risk of internal malignancy, most often adenocarcinoma.
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(B) Anti-Mi2 autoantibodies are myositis specific autoantibodies with a low prevalence in the setting of dermatomyositis.
They are seen in the highest frequency in patients presenting with classic adult onset dermatomyositis with Gottron’s
papules, Gottron’s sign, the shawl sign (violaceous poikiloderma around the neck) and frayed cuticles.
(C) Anti-Jo1 autoantibodies are another myositis-specific autoantibody that targets the aminoacyl transfer RNA
synthetase enzymes responsible for delivering amino acids to ribosomes in order for protein translation to take place.
Patients with these autoantibodies are often defined as having the antisynthetase syndrome. Patients with them,
however, are more prone to developing arthritis, Raynaud’s phenomenon, and interstitial lung disease. Mortality is more
often due to interstitial lung disease, however in this subset of DM patients, the lung disease is not as rapidly progressive
as is demonstrated in the anti-MDA5/CADM140 patients.
(E) Anti-MDA5/CADM-140 autoantibodies are associated with a distinct clinical phenotype in patients with
dermatomyositis. These patients experience tender palmar papules, painful cutaneous ulcerations, oral pain, alopecia,
with an increased mortality secondary to rapidly progressive interstitial lung disease.
11. Primary and secondary Raynaud’s phenomenon have different features that allow them to be differentiated. Which
of the following choices would suggest a secondary form of Raynaud’s phenomenon?
A. Onset at puberty
B. Emotional stress as a trigger
C. Normal capillaroscopy
D. 10 attacks per day
E. Negative antinuclear antibodies
Correct answer: (D) 10 attacks per day.

Explanation: Primary Raynaud’s is considered benign and most frequently involves women. It’s age of onset is at
puberty, whereas an age of onset >25 years would orient towards a secondary form. The frequency of attacks is usually
<5 per day and having from 5 to 10 a day would suggest a secondary form. Precipitants for both forms include cold but
emotional stress is more suggestive of a primary form. The presence of ischemic injury, abnormal capillaroscopy,
antinuclear antibodies, anticentromere antibody, anti-topoisomerase I (Scl-70) antibody or In vivo platelet activation
would also warrant the investigation for a secondary cause.
12. A patient presents to your clinic with complaints of an urticarial-like rash that is periodically associated with lower
extremity bone pain and fevers. The urticaria is not pruritic and you suspect a diagnosis of Schnitzler syndrome.
Which of the following lab tests would support this diagnosis?
A. Serum ferritin
B. Complement levels
C. Serum and urine protein electrophoresis
D. Rheumatoid factor
E. Anti-nuclear antibody
Correct answer: (C) Serum and urine protein electrophoresis.

Explanation: The next step in management of patients you suspect of having a diagnosis of Schnitzler syndrome is to
perform an SPEP/UPEP (serum/urine protein electrophoresis) to assess for the associated monoclonal IgM gammopathy.
(A) Serum ferritin is elevated in both systemic-onset juvenile idiopathic arthritis and adult-onset Still’s disease. (B) While
angioedema can occur in up to 15% of patients with Schnitzler syndrome, complement level alterations do not aide in the
diagnosis of Schnitzler syndrome. (D) (E) Rheumatoid factor and ANA elevation are not associated findings of Schnitzler
syndrome.
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13. This condition can present with the following cormorbidities:
A. pustules on the hands and soles

B. chronic osteomyelitis of the clavicle
C. hepatitis
D. arthritis mutilans
E. A&B
Correct answer: (E) A & B. Pustules on the hands and soles and chronic osteomyelitis of the clavicle.
Explanation: Both A & B are true statements regarding SAPHO syndrome.
(A) SAPHO syndrome is a neutrophilic dermatosis that presents with cutaneous pustulosis and acne. The acronym includes
synovitis, acne, pustulosis, hyperostosis, and osteitis. Palmar and plantar pustulosis is associated with the condition.
(B) Chronic recurrent osteomyelitis is one of the key features of SAPHO syndrome, and classically involves the sternum,
clavicle, and ribs.
(C) Hepatitis is not classically associated with SAPHO syndrome.
(D) Arthritis mutilans is associated with severe, chronic cases of multicentric reticulohistiocytosis, not SAPHO syndrome.
14. Which of the following immunofluorescent ANA patterns demonstrates the greatest degree of specificity?
A. Homogeneous (diffuse) pattern
B. Peripheral (rim) pattern
C. Speckled pattern
D. Centromeric pattern
E. Nucleolar pattern
Correct answer: (D) Centromeric pattern.

Explanation: Immunoflourescent ANA patterns do not typically lend a significant amount of specificity enabling the
clinician to establish a diagnosis. The one exception to this rule is the Centromeric pattern, which is a pattern that is
strongly, and specifically associated with the limited form of systemic sclerosis (SSc). The Centromeric pattern, or discrete
speckled pattern, results from antibody binding to the polypeptide components of chromosomal centromeres.
(A) The homogenous or diffuse pattern is associated with systemic lupus erythematosus (SLE), mixed connective tissue
disease, and drug-induced lupus.
(B) The peripheral or rim pattern likely targets autoantibodies to DNS including double-stranded DNA and is most
suggestive of SLE, but can be seen in other autoimmune connective tissue diseases.
(C) The speckled pattern is associated with SLE, Sjögren syndrome, scleroderma, polymyositis, rheumatoid arthritis, and
mixed connective tissue pattern.
(E) The Nucleolar pattern is associated with scleroderma and polymyositis.
15. A post-pubertal woman afflicted by the diffuse skin hyperpigmentation with accentuation in sun-exposed areas and
loss of ambisexual hair should undergo which following test to establish the correct endocrinopathy diagnosis?
A. Triglyceridemia
B. Adrenocorticotropic hormone stimulation test
C. Fasting blood glucose
D. Ferritin
E. Thyroid stimulating hormone
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Correct answer: (B) Adrenocorticotropic hormone stimulation test.
Explanation: The clinical picture is one of Addison’s disease (AD). Plasma levels of ACTH are elevated in primary
adrenocortical insufficiency (Addison’s disease) whereas they are suppressed in secondary adrenocortical insufficiency
(due to exogenous corticosteroids). Hypertriglyceridemia may be found in metabolic syndrome and in eruptive
xanthomas, both of which do not present with such a clinical picture. An elevated fasting blood glucose may be found in
the the metabolic syndrome or diabetes mellitus. A greatly elevated level of ferritin may be suggestive of
hemochromatosis in which bronzing of the skin is found but not loss of ambisexual hair. Finally, high or low levels of TSH
(thyroid stimulating hormone) have many skin findings, but none involve the loss of ambisexual hair.
16. A patient suffering from a drug induced systemic lupus erythematosus is most likely to have auto-antibodies against
which of the following choices?
A. Double stranded DNA (dsDNA)
B. Single stranded DNA (ssDNA)
C. U1RNP
D. Cardiolipin
E. Histones
Correct answer: (E) Histones.

Explanation: A patient suffering from a drug induced systemic lupus erythematosus is most likely to have auto-antibodies
against histones (anti-histone antibodies). The other targets are associated with other diseases. Double stranded DNA
(dsDNA) is associated with lupus nephritis. Single stranded DNA (ssDNA) is seen as a possible risk factor for systemic
lupus erythematosus in discoid lupus patient. ssDNA is also seen in other auto-immune connective tissue diseases such as
rheumatoid arthritis, juvenile diabetes mellitus, mixed connective tissue disease, systemic sclerosis, Sjögren’s syndrome
and morphea. U1RNP is seen in 100% of mixed connective tissue disease.
Finally, cardiolipin is associated with recurrent spontaneous abortions, thrombocytopenia, and hypercoagulable state in
systemic lupus erythematosus. The dermatological manifestations include livedo reticularis, leg ulcers, acral infarction
and ulceration as well as hemorrhagic cutaneous necrosis. Similar associations are found in primary antiphospholipid
antibody syndrome and the clinical manifestations have an association with IgG class of anticardiolipin.
17. A 45 year-old patient whom you have been following in your clinic returns for a follow-up discussion after a biopsy
demonstrating the poikilodermatous skin changes around his neck were consistent with the diagnosis of
dermatomyositis. He continues to experience no muscle weakness. Which of the following positive lab findings would
most likely put this patient at increased risk for adenocarcinoma?
A. anti-p155 autoantibodies
B. anti-Mi2 autoantibodies
C. anti-Jo1 autoantibodies
D. anti-SRP autoantibodies
E. anti-MDA5/CADM-140 autoantibodies
Correct answer: (A) Anti-p155 autoantibodies.

Explanation: In one study, 80% of adult patients with amyopathic (no skeletal muscle involvement) dermatomyositis,
papules, Gottron’s sign, the shawl sign (violaceous poikiloderma around the neck) and frayed cuticles. This autoantibody
does not increase the risk of internal malignancy.
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Patients with these autoantibodies are often defined as having the antisynthetase syndrome. Like anti-Mi2
autoantibodies the prevalence of anti-Jo1 autoantibodies is relatively low. Patients with them, however, are more prone
to developing arthritis, Raynaud’s phenomenon, and interstitial lung disease. Mortality is more often due to interstitial
lung disease and not an increased risk for internal malignancy.
(D) Anti-SRP (signal recognition particle) autoantibodies are associated with fulminant dermatomyositis with an
increased mortality rate secondary to cardiac involvement. Prevalence of these autoantibodies is lower then anti-Mi2
and anti-Jo1 autoantibodies. There is no increased risk of internal malignancy associated with this autoantibody.
(E) Anti-MDA5/CADM-140 autoantibodies are associated with a distinct clinical phenotype in patients with
with an increased mortality secondary to rapidly progressive interstitial lung disease. The prevalence of these
autoantibodies parallels that of anti-Mi2 and Jo1 autoantibodies, but is higher than anti-SRP autoantibodies. There is no
increased risk of internal malignancy associated with this autoantibody.
18. A 12 year-old male is referred to your clinic because of a recurrent erythematous rash involving the axillae and waist
that appears to accompany arthralgias of multiple joints symmetrically. The rash is not symptomatic and the patient
denies pruritus. Which of the following lab findings would most specifically support a presumed diagnosis of
systemic-onset juvenile idiopathic arthritis (Still’s Disease)?
A. Leukocytosis
B. Elevated ferritin
C. Elevated ESR
D. Positive ANA
E. Positive rheumatoid factor
Correct answer: (B) Elevated ferritin.

Explanation: In both systemic-onset juvenile idiopathic arthritis (SoJIA) and adult-onset Still’s disease, a ferritin level
greater than 4000, while not diagnostic, is strongly supportive of the presumed diagnosis. There is no laboratory value,
elevated or decreased, that is completely specific for either of these autoinflammatory diseases. In addition to
leukocytosis (Choice A) and an elevated ESR (Choice C), additional significant but non-specific laboratory findings include
thrombocytopenia, an elevated C-reactive protein, and elevated heaptic enzymes. Patients with a diagnosis of SoJIA
rarely demonstrate a positive ANA (Choice D) or rheumatoid factor (Choice E).
19. Which of the following is the strongest factor affecting the risk for the development of systemic lupus erythematosus?
A. Sex
B. Ethnicity
C. Age
D. Chronic sun exposure
E. Other autoimmune disease
Correct Answer:A. Sex.

Explanation: The strongest factor predisposing patients to the development of systemic lupus erythematosus (SLE) is sex.
There is a 6:1 female to male ratio of patients with SLE.
Incorrect Answers:
B. Additionally, ethnicity, with an increased risk in African americans when compared to Caucasians, also increases the
risk of developing SLE. One study found a prevalence of 4 in 1000 African American patients with SLE compared to 1 in
1000 Caucasians.
C. Age also affects risk, with women in their childbearing years at greatest risk.
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D. Chronic sun exposure may be an environmental trigger in patients with underlying disease or susceptibility, but this
factor does not increase the risk of developing SLE in healthy patients.
E. SLE may overlap with other autoimmune disease such as Hashimoto’s Thyroiditis or Grave’s Disease, and this poses a
genetic HLA susceptibility, but does not singularly increase the risk of developing systemic lupus.
20. A 45 year-old female presents to you clinic with symptoms of xerostomia (dry mouth) and xerophthalmia (dry eyes),
both of which have been confirmed by objective testing using a sialogram and Schirmer test respectively. In order to
make a diagnosis, which of the following additional objective criteria must be met?
A. Positive autoantibodies to either Ro or La
B. Positive salivary gland biopsy
C. Either choice A or B
D. Both choice A and B
E. None of the above is required to make a diagnosis
Correct answer: (C) Either choice A or B.

Explanation: A diagnosis of Sjögren Syndrome (SjS) requires both subjective and objective evidence before it can be
rendered. These criteria were established by the European-American Consensus Group for the Diagnosis of Sjögren
Syndrome. The criteria consist of the following: - Three or more of the following: Symptoms of xerophthalmia, Objective
evidence of xerophthalmia (a positive Schirmer test, Rose Bengal test) both of which measure lacrimation, Symptoms of
xerostomia, Objective signs of impaired salivary gland function (sialogram, scintigraphy). - Additionally, one of the
following must be present: Positive salivary gland biopsy demonstrating findings consistent with SjS and/or Presence of
autoantibodies (anti-Ro/SS-A or anti-La/SSB). In the previous vignette, the patient already presents with both subjective
and objective findings of a presumed diagnosis of SjS, and requires either a salivary gland biopsy consistent with that of
SjS or the presence of autoantibodies. Both are not required to make the diagnosis, and this should be kept in mind in
patients whom do not wish to undergo a procedure. Positive serology OR a positive biopsy with the additional criteria
listed above, has a diagnostic sensitivity and specificity of 97 and 90% respectively.
21. Which of the following is false regarding the condition below?
A. sildenafil can be used to improve hand dexterity

B. anti-topoisomerase antibodies are associated with
limited disease
C. pulmonary function testing should be performed
D. abnormal barium swallow testing may be seen
E. None of the above
Correct answer: (B) Anti-topoisomerase antibodies are associated with limited disease.
Explanation: Anti-topoisomerase antibodies (anti-SCL70) are associated with systemic sclerosis or diffuse scleroderma.
Limited sclerosis (CREST syndrome) presents with calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, and
telangiectases, and serologically demonstrates anti-centromere antibody positivity.
(A) The condition shown above is scleroderma, which in chronic cases may present with diffuse salt-and-pepper hyper-
and hypo-pigmentation. Sildenafil (Viagra) is a selective inhibitor of phosphodiesterase-5 (PDE5). Inhibition of PDE5
produces an increase in cyclic guanosine monophosphate (cGMP), and subsequent vasodilation. Improvement in
dexterity in patients with Raynaud’s has been shown with Sildenafil.
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(C) Patients with systemic sclerosis should be evaluated for pulmonary disease. Pulmonary function testings (PFTs) should
be ordered.
(D) Esophageal dysmotility may develop with scleroderma.
22. All of the following diagnostic tools can be used to follow and monitor muscle inflammation in dermatomyositis
EXCEPT?
A. Electromyography
B. Computerized tomography scan
C. Magnetic resonance imaging
D. Ultrasound
E. Serum level of muscle enzymes
Correct answer: (B) Computerized tomography scan.

Explanation: Use of serial CT scans to follow and monitor muscle inflammation has not shown efficacy in patients with
dermatomyositis, additionally, they expose patients to un-necessary doses of radiation. Electromyography, is a sensitive
but non-specific test in patients with DM. This modality is useful in monitoring flares in disease as over 90% of patients
with active DM will have abnormal results. Abnormal EMG findings in combination with cutaneous lesions of DM,
confirmed histologically, can be used to make the diagnosis of DM. Both magnetic resonance imaging and ultrasound
imaging can demonstrate visual evidence of inflammation associated with the changes seen in dermatomyositis (Choices
C and D). Serum levels of muscle enzymes, such as creatine kinase, aldolase, and myoglobinurea are often used to
diagnose, and follow disease progression and response to therapy in patients with dermatomyositis (Choice E).
23. Autoantibodies can be useful in the diagnosis, management and prognosis of the autoimmune connective tissue
diseases (AI-CTDs), but their interpretation is even more important. An example of that resides in the interpretation
of the anti-nuclear antibody (ANA) test. What percentage of the normal and healthy population can have a positive
ANA and report a titer of 1 :80 that has no clinical significance?
A. 25%
B. 13%
C. 8%
D. 5%
E. 3%
Correct answer: (B) 13%.

Explanation: The ANA titer that is considered to be abnormal varies significantly. This depends upon how the assay is
performed and interpreted. Many laboraties consider an ANA titer of 1 : 40 or 1 : 80 to be abnormal. This is most
probably because accepting such relatively low levels of ANA as being abnormal retains a high degree of sensitivity of
the ANA assay in detecting systemic auto-immune connective tissue diseases. Using such low ANA titer cut-offs creates a
lot of positive, but clinically insignificant, ANA test results. The specificity is therefore reduced. Many studies comparing
ANA results in lupus erythematosus populations with those in normal control populations have shown that a titer of <1 :
160, using a human tumor cell line substrate, has little clinical utility. A report based upon 15 international laboratories
showed the following results:
- The ANA positivity rate in a population of healthy individuals (thus false positives) in between the ages 20–60 years was :
 13.3% at 1:80 (this is the answer to the question, rounded to 13%)
 5.0% at 1:160
 3.3% at 1:320
It is important to know that the elderly, the relatives of those with systemic lupus erythematosus, the patients with other
autoimmune disorders such as autoimmune thyroid disease and the healthy individuals, may have abnormally elevated
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ANA titers without clinical significance. For your information, the 25% and 8% are distractors and do not represent any
relevant statistics for the current question.
24. A 50 year old patient has severe and chronic urticaria, unresponsive to high doses of H1 antihistamines as well as
leukotriene inhibitors. The decision is made to start omalizumab. Which of the following is a potential serious adverse
reaction to omalizumab?
A. Renal failure
B. Congestive heart failure
C. Anaphylaxis
D. Progressive multifocal leukoencephalopathy
E. Reactivation of latent tuberculosis
Correct answer: (C) Anaphylaxis.

Explanation: Omalizumab, a recombinant humanized monoclonal anti-IgE antibody was first approved for asthma but is
now being used for chronic urticaria. The medication is generally well tolerated but carries a risk of potentially life
threatening risk of anaphylaxis. Anaphylaxis has occurred in less than 1% of patients treated with omalizumab, and no
anaphylactic reactions were seen in the trials for urticaria, never the less the medication contains a black box warning.
(A) Renal failure has not been reported to be associated with omalizumab
(B) Worsening congestive heart failure has been associated with TNF inhibitors
(D) Progressive multifocal leukoencephalopathy was associated with the psoriasis biologic efalizumab which was
withdrawn from the market in 2009. Other cases of PML have been associated with TNF inhibitors and rituximab.
(E) Reactivation of latent tuberculosis has been seen in patients undergoing therapy with TNF inhibitors.
25. A patient presents to your clinic for a second opinion about her diagnosis and associated lab results. She was initially
seen by her primary care physician for mild joint pain associated with a facial rash that comes and goes and was
described as photosensitive by the patient. She states that labs were done revealing an elevated ANA. Which of the
following conditions can be associated with positive ANA titers in the absence of lupus?
A. Autoimmune thyroiditis
B. Pernicious anemia
C. Minocycline
D. Healthy individuals
E. All of the above
Correct answer: (E) All of the above.

Explanation: All of the above choices can lead to an elevated ANA without insinuating a diagnosis of a connective tissue
disease such as dermatomyositis or systemic lupus erythematosus. The estimated sensitivity of ANA is approximately
98% however, its specificity is only 90%, meaning it is more difficult to rule-in the diagnosis of a mixed connective tissue
disease if a patient demonstrates a positive ANA. The reasons for this are represented in choices A-D.
(A) (B) Autoimmune diseases such as Grave’s Disease, Hashimoto’s Thyroiditis, and Pernicious anemia can contribute to a
positive ANA in patients with autoimmune dermatologic disorders such as vitiligo and alopecia areata.
(C) Medications such as minocycline and hydralazine can lead to drug-induced lupus and also cause elevated ANA levels.
Additional testing including histone antibodies, should be performed if there is suspicion for drug-induced lupus, and will
aide in the extrapolation of a positive ANA.
(D) To confound matters more, healthy patients can exhibit a positive ANA which increases in incidence as the cut-off for
positivity increases. For instance, if a titer of 1:80 is interpreted as positive, 13.3% of a healthy population can
demonstrate a positive ANA. Similarly, when the titer cut-off is decreased to 1:160 and 1:320, corresponding positive
findings in a healthy population decrease to 5.0% and 3.3% respectively. This highlights two important factors in the
interpretation of an ANA titer. The first is that different labs may have a different cut-off for what can be interpreted as
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positive, and secondly, a significant number of healthy individuals can demonstrate a positive ANA regardless of the cut-
off level used.
26. Which autoantibody would you expect to be elevated in a patient you suspect may have dermatomyositis and presents
with hyperkeratotic and fissured skin on the palmar and lateral aspects of the phalanges, arthritis, myositis and
Raynaud's disease?
Correct answer: (C) Anti-Jo1 autoantibodies.

Explanation: Myositis specific serum autoantibodies in dermatomyositis may be correlate with particular clinical
features. (C) Anti-Jo1 autoantibodies, correct. The anti aminoacyl-transfer RNA antibody, anti Jo-1, is associated with the
constellation of findings known as the antisynthetase syndrome. Clinical features include interstitial lung disease,
raynaud’s disease, arthritis and mechanic hands.
(A) Anti p155 autoantibodies, incorrect. Anti p155 autoantibodies are associated with an increased risk of internal
malignancy. The classic cutaneous features of dermatomyositis may be present.
(B) Anti Mi2 autoantibodies, incorrect. Anti-helicase antibodies are associated with the characteristic cutaneous features
of dermatomyositis: Gottron’s papules (violaceous papules on the MCP and IP joints), Gottron’s sign, ragged cuticles, and
the shawl sign (photodistrubuted poklioderma). Myopathy is mild.
(D) Anti-SRP autoantibodies, incorrect. Anti-SRP autoantibodies are associated with severe and progressive necrotizing
myopathy.
(E) Anti-MDA5/CADM-140 autoantibodies, incorrect. Anti-CADM-140 autoantibdoes are associated with amyopathic
dermatomyositis with rapidly progressive interstitial lung disease.
27. All of the following treatments of systemic lupus erythematosus and their side effects are paired correctly EXCEPT?
A. Chloroquine and eye toxicity
B. Thalidomide and sedation
C. Thalidomide and peripheral neuropathy
D. Quinacrine and yellowing of the skin
E. Quinacrine and eye toxicity
Correct answer: (E) Quinacrine and eye toxicity.

Explanation: It is important to understand the side effects associated with the systemic therapies often used in the
treatment of systemic lupus erythematosus given the chronicity of the disease and the need for long-term medical
therapy. Quinacrine has not been associated with eye toxicity, unlike hydroxychloroquine and chloroquine (Choice A).
The most common side effect of quinacrine is yellowing of the skin (Choice D), and is sometimes described as an orange-
yellow tint that is easily distinguished from yellowing of the skin seen in jaundice. Thalidomide, often reserved for major
organ involvement in SLE, has numerous side effects of which sedation is the most common. Peripheral neuropathy is less
common than sedation, but is still a side effect that should be frequently monitored for (Choice B and C). This medication
has dire consequences in women of childbearing potential including phocomelia (abnormal dysmorphic appendages),
and should not be administered in this patient population.
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28. Which of the following features of dermatomyositis occurs more frequently in childhood cases of the condition?
A. Heliotrope rash
B. Interstitial lung disease
C. Relation to malignancy
D. Calcinosis cutis
E. Periungual telangiectasias
Correct answer: (D) Calcinosis cutis.

Explanation: Calcinosis cutis. Interstitial lung disease and relation to malignancy are more common in adult cases of
dermatomyositis, while features such as calcinosis cutis are more common in pediatric cases of dermatomyositis.. The
presence of heliotrope rash and periungual telangiectasias does not differ in age affected.
29. A 68 year-old woman presents to your clinic with an erythematous rash affect the cheeks bilaterally as well as the
bridge of her nose. She states she has no significant past medical history or notable family history. Which of the
following laboratory studies would be most appropriate to perform initially?
A. ANA
B. dsDNA
C. Anti-Jo 1 antibodies
D. Scl-70
E. Anti-Ro antibodies
Correct answer: (A) ANA.

Explanation: The hallmark of autoimmune connective tissue diseases is the presence of circulating auto-antibodies. The
most commonly performed laboratory exam when there is suspicion of an autoimmune connective tissue disease is the
measurement of anti-nuclear antibodies (ANA). The patient in the vignette presents with one of the cardinal signs of
systemic lupus erythematosus, the malar rash. The findings of a bilaterally erythematous facial rash can also represent
other dermatologic conditions such as rosacea or sunburn. If the suspicion for a connective tissue disease is present, the
initial test of choice is the anti-nuclear antibody titer. It is also more cost-effective then submitting an entire panel for the
testing of various other autoantibodies.
(B) Anti-double stranded DNA antibodies (dsDNA) are specific for lupus erythematosus and can also be used to monitor
disease severity. A higher titer of dsDNA correlates to a higher risk of lupus nephritis.
(C) Anti-Jo 1 antibodies are myositis specific antibodies directed at aminoacyl tRNA. It is also know as the anti-synthetase
antibody.
(D) Antibodies to Scl-70 are specific for systemic sclerosis.
(E) Anti-Ro or anti-SSA antibodies are often the markers for the lupus variant of subacute cutaneous lupus erythematosus
(SCLE), but can also be found in neonatal lupus, Sjogrens Syndrome, and vasculitides.
30. A 65 year old male presents with a several week history of symmetric ill defined indurated plaques on the lower
extremities proximally to the knees. He complains of difficulty moving his knees and there is a substantial loss of
motion on exam. Laboratory evaluation is significant for a creatinine of 3.6, and negative anti-nuclear antibody. A
punch biopsy shows fibroblast proliferation, thickened collagen bundles and mucin deposition. Spindled fibroblasts
stain positive for CD34. What is the most likely diagnosis in this patient?
A. Scleromyxedema
B. Nephrogenic Systemic Fibrosis
C. Scleroderma
D. Graft versus host disease
E. Scleredema
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Correct answer: (B) Nephrogenic Systemic Fibrosis.
Explanation: Nephrogenic systemic fibrosis is a disorder caused by the administration of a gadolinium containing contrast
agent in patients with a history of renal disease. The cutaneous features are characterized by a progressive fibrosis along
the distal extremities, and joint involvement can result in severe flexion contracture. Histology of nephrogenic systemic
fibrosis shows CD34+ positive fibroblasts with thickened collagen bundles and abundant mucin deposition.
(A) Scloeromyxedema is a disorder of mucinous deposition in the skin associated with a monoclonal gammopathy.
Histopathological features of scleromyxedema are identical to nephrogenic systemic sclerosis with mucin deposition,
thickened collagen bundles and increased fibroblasts. Fibroblasts in scleromyxedema would also be CD34+ positive.
(C) While scleroderma can present with skin fibrosis and renal involvement, in scleroderma serological markers for
autoimmunity would be present. The patient in the question stem had a negative ANA.
(D) Chronic graft versus host disease can present with a sclerodermoid like cutaneous eruption, the histological findings
mimic scleroderma with thickened collagen bundles arranged parallel to the epidermis.
(E) Scleredema is a disorder of mucinous deposition that occurs in the setting of diabetes, streptococcal infection or
monococcal gammopathy. A non pitting induration is typically seen on the neck. Unlike scleromyxedema and nephrogenic
systemic fibrosis there is no increase in fibroblasts on histological examination.
31. A patient presents to your clinic after being seen by a rheumatologist for a work up of his arthritis. He was referred
to you because of 2-3 erythematouos papules which join to form one annular plaque on his distal extremities. The
lesion has grown over a period of several months. The referral note expresses confusion about his diagnosis of
rheumatoid arthritis since the patient had been classified as seronegative following several negative rheumatoid
factor lab studies. No distal joints are involved and his arthritis is asymmetric. On exam, there is no nail pitting or
oncholysis. Which of the following is the best explanation for his cutaneous findings?
A. Regardless of the lab studies this patient has rheumatoid arthritis and these are rheumatoid
nodules
B. These lesions likely represent subcutaneous granuloma annulare
C. The patient likely developed these lesions after initiating treatment with methotrexate for his
arthritis
D. The patient likely developed these lesions after initiating treatment with a tumor necrosis factor
alpha inhibitor
E. None of the above explains the patient’s lesions
Correct answer: (B) These lesions likely represent subcutaneous granuloma annulare.
Explanation: Studies examining biopsies in patients with seronegative rheumatoid arthritis (RA) demonstrated that a
majority of the nodules biopsied represented subcutaneous granuloma annulare and were not rheumatoid nodules.
Rheumatoid nodules do not usually develop in patients with negative serology for rheumatoid factor (RF), also known as
seronegative RA. In the above vignette, evidence supports that these lesions are either presenting signs of granuloma
annulare or represent palisaded granulomas associated with connective tissue diseases like rheumatoid arthritis. Repeat
testing for RF, does not help with the diagnosis in these particular cutaneous findings (Choice A). Following initiation of
either methotrexate or TNF-alpha receptor inhibitors in patients with RA has been known to lead to the onset in
appearance of multiple rheumatoid nodules. The rheumatoid nodules associated with these medications (Choice C and D)
have a rapid onset, and appear in multitude explaining the terminology used behind this clinical condition, accelerated
nodulosis. In a patient with seronegative RA, a biopsy of the nodule is necessary to make a distinct diagnosis.
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32. Which of the following is false regarding relapsing polychondritis?
A. May lead to saddle nose deformities
B. Associated with Type I collagen antibodies
C. Associated with HLA-DR4
D. May be treated with systemic corticosteroids
E. Can affect any cartilagenous location
Correct answer: (B) Associated with Type I collagen antibodies.

Explanation: Relapsing polychondritis is associated with Type II collagen antibodies (not Type I).
(A) Chronic and severe forms of relapsing polychondritis may be complicated by saddle nose deformities.
(C) Relapsing polychondritis is associated with HLA-DR4.
(D) Relapsing polychondritis may be treated with systemic corticosteroids.
(E) Any cartilagenous location can be affected in relapsing polychondritis.
33. A patient, who was recently prescribed a new medication for presumed tuberculosis is referred to your clinic for
“drug-induced Lupus.” Which of the following statements regarding this condition is FALSE?
A. Cutaneous lesions are often present including the malar rash and discoid lesions
B. Drug-induced lupus does not present with central nervous system disease
C. Drug-induced lupus does not present with, or is complicated by nephritis
D. Anti-histone antibodies are often positive in cases of drug-induced lupus
E. Drug-induced lupus can present with arthralgias, myalgias, pleuritis and fever
Correct answer: (A) Cutaneous lesions are often present including the malar rash and discoid lesions.
Explanation: All of the statements regarding drug-induced lupus in choices B-E are correct. Cutaneous lesions, similar to
those seen in systemic lupus erythematosus (such as the malar rash, and discoid lesions) are particularly rare clinical
findings in patients with drug-induced lupus. The patient in question was likely taking isoniazid, an anti-mycobacterial
antibiotic often implicated in drug-induced lupus. Cutaneous lesions in drug-induced lupus are not prominent features of
this lupus mimic, and only approximately 25% of patients with drug-induced lupus will present with cutaneous lesions.
Drug-induced lupus does not involve the central nervous system, and is not a known risk factor for nephritis associated
with lupus, however, patients can have other features of systemic lupus erythematosus, and clinic suspicion should
remain high in patients presenting with fever, arthralgias, myalgias, and pleuritis following the consumption of a new
medication. Submitting laboratory analysis to rule out SLE, and drug-induced lupus (including serum anti-histone
antibodies) is not unreasonable given the similarities between the two entities
34. Which of the following is not a characteristic of tumid lupus?

A. Histopathologically, the inflammation is located in the dermis, with no epidermal invovlement
B. Lesions of tumid lupus can present as edematous plaques
C. There is typically no dyspigmentation or follicular plugging in lesions of tumid lupus
D. Lesions tend to heal with scarring and atrophy
E. Lesions of tumid lupus are reproducible by phototesting
Correct answer: (D) Lesions tend to heal with scarring and atrophy.
Explanation: The inflammatory infiltrate seen on pathologic examination of lesions of tumid lupus is located primarily in
the dermis with little to any involvement of the epidermis or adnexae (Choice A). For this reason, there is typically no
dyspigmentation or follicular plugging (Choice C) seen in lesions of tumid lupus as opposed to those of discoid lupus. The
lack of epidermal inflammation is the underlying reason that lesions tend to heal without the scarring and atrophy
demonstrated in discoid lesions, where the underlying inflammatory infiltrate involves the superficial dermis and dermal-
epidermal junction. Lesions of tumid lupus can often appear edematous or swollen, akin to urticarial plaques, and may or
15
may not be erythematous (Choice B). Close inspection of these lesions reveals a lack of surface changes like scale,
follicular plugging, hyper or hypopigmentation. Lesions of tumid lupus are reproducible by phototesting unlike discoid
lesions.
35. When considering extensive acanthosis nigricans with the involvement of the palms and soles, which other
characteristics are the most important to look for?
A. Sudden onset and weight loss
B. Overweight patient or obesity
C. Striae, hypertension, central obesity and buffalo hump
D. Female, acne, hirsutism, irregular menses
E. Medications such as oral contraceptives, niacin, corticosteroids or protease inhibitors
Correct answer: (A) Sudden onset and weight loss.

Explanation: When considering extensive acanthosis nigricans (AN) with involvement of the palms and soles, the sudden
onset of AN accompanied by weight loss should prompt for the evaluation for an underlying malignancy or restaging if
the patient has a known malignancy. Therefore, the sudden onset with weight loss orient towards a malignancy and are
the correct combination of signs and symptoms to look for. All other choices are also associated with AN but not
malignancy related. Overweight and obese patients can suffer from insuline resistance, diabetes or thyroid disease.
Cushing syndrome can involve AN and has the following characteristics: striae, hypertension, central obesity and buffalo
hump. Polycystic ovary syndrome is found in women with acne, hirsutism, irregular menses and sometimes AN.
Medications such as oral contraceptives, niacin, corticosteroids or protease inhibitors can cause AN, but the onset is
usually not sudden and weight loss is not a feature.
36. Bazex syndrome, otherwise known as acrokeratosis paraneoplastica is associated with which type of neoplasia?
A. Mid-gut tumors with liver metastases
B. Plasmocytoma
C. Small cell carcinoma of the lung
D. Glucagon-secreting tumor of the pancreas
E. Upper aerodigestive tract malignancy
Correct answer: (E) Upper aerodigestive tract malignancy.

Explanation: Bazex syndrome, otherwise known as acrokeratosis paraneoplastica is associated with upper aerodigestive
tract malignancies (pharynx, larynx or esophagus). Plasmocytoma can be associated with large red to violet–brown
patch called AESOP syndrome (adenopathy, extensive skin patch overlying (a) plasmacytoma). Small cell carcinoma of
the lung may involve the production of ACTH by the tumor and may result in skin hyperpigmentation and features of
Cushing’s syndrome. Glucagon-secreting tumor of the pancreas causes glucagonoma syndrome with the following
features: necrolytic migratory erythema, angular cheilitis and glossitis. Mid-gut tumors with liver metastases can be the
cause of flushing in the event of carcinoid syndrome.
37. What percentage of adults with discoid lesions will develop systemic lupus erythematosus (SLE) as defined by the
criteria established by the American College of Rheumatology?
A. There is no associated risk of developing SLE in patients with discoid lesions
B. 5-15% of patients with discoid lesions will develop SLE
C. 30-40% of patients with discoid lesions will develop SLE
D. 60-75% of patients with discoid lesions will develop SLE
E. SLE develops in more than 75% of patients with discoid lesions
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Correct answer: (B) 5-15% of patients with discoid lesions will develop SLE.
Explanation: Approximately 5-15% of patients with the discoid lesions of discoid lupus erythematosus will go on to
develop systemic lupus erythematosus as defined by the 11 criteria set forth by the American College of Rheumatology
ACR. There are some published studies pointing to an increased risk for the development of SLE in patients whose discoid
lesions are extensive and involve anatomic areas below the head and neck. It is important to note, that one of the 11
criteria for SLE is the presence of discoid lesions.
38. Which of the following regarding this condition is true?
A. associated with an IgG lambda paraproteinemia

B. histologically characterized by mucin deposition,
increased collagen deposition, and proliferation
of irregularly arranged fibroblasts
C. thyroid function tests should be ordered, and are
expected to be normal
D. examination of the proximal interphalangeal joint
(PIP) may reveal induration surrounding a centrally
depressed area (termed donut sign)
E. all of the above are true
Correct answer: (E) All of the above are true.

Explanation: All the statements (A) (B) (C) (D) are true statements.
(A) Scleromyxedema is associated with an IgG lambda paraproteinemia.
(B) Histologically, scleromyxedema is associated with a triad of microscopic features: a diffuse deposit of mucin in the
upper and mid-reticular dermis, an increase in collagen deposition, and a marked proliferation of irregularly arranged
fibroblasts.
(C) Since the histologic differential diagnosis of scleromyxedema includes pretibial myxedema, thryoid function testing
should be ordered. Normal thyroid function is expected in scleromyxedema.
(D) The ‘donut’ sign describes induration surrounding a centrally depressed area, typically along the PIP joint. This
finding is classically associated with scleromyxedema.
39. Which of the following associations is incorrect?

A. Vit A-Perifollicular keratosis
B. Vit K-Purpura
C. Niacin-Photodermatitis
D. Copper-Pili torti
E. Magnesium-Paronychial pustulosis
Correct answer: (E) Magnesium-Paronychial pustulosis.

Explanation: Zinc (not magnesium) may present with a pustular paronychia. Zinc deficiency also presents with a
periorificial dermatitis, diarrhea, and alopecia.
(A) Vitamin A deficiency is associated with follicular hyperkeratosis or phrynoderma (‘toad skin’), which clinically appears
as follicular papules with a central keratotic plug.
(B) Vitamin K deficiency impairs the coagulation cascade, and subsequently may lead to purpuric skin lesions and
ecchymoses.
17
(C) Niacin (B3) deficiency underlies pellagra, which is associated with a photosensitive dermatitis that appears
hyperpigmented and scaly in chronic cases. A shellac-like appearance has been described in persistent cases. Casal’s
‘necklace’ describes the localized photosensitive eruption around the neck which can often develop.
(D) Inherited impairment of copper transport include Wilson’s disease and Menkes’ syndrome (also known as kinky hair
disease). Menkes’ presents with twisted hairs (pili torti).
40. What is the associated virus for the condition below?
A. HHV-7
B. HHV-8
C. Hep B
D. Hep C
E. EBV
Correct answer: (B) HHV-8.

Explanation: HHV-8 aka Kaposi’s sarcoma-associated herpesvirus is a latent virus found in the vast majority of all types
of Kaposi’s sarcoma worldwide. The classic form of KS is typically found in men of Mediterranean and Ashkenazi Jewish
descent in their sixth decade of life. Classic lesions initially develop as purplish-red plaques primarily on the lower legs of
elderly men. The disease generally has a slow progression. In addition to the classic form of KS there are: HIV associated,
African endemic, and drug-induced immunosuppression associated forms. AIDS related is more widespread and presents
as small macules, patches, or plaques, but can become exophytic and ulcerative. Approximately 80% of AIDS patients
with KS will develop GI involvement. The second most common process associated with HHV-8 is Castleman’s disease.
(A) HHV-7 is associated with exanthem subitum (Sixth Disease, Roseola Infantum).
(C) Hep B is associated with Giannoti-Crosti syndrome.
(D) Hep C is associated with lichen planus, porphyria cutana tarda, polyarteritis nodosa, cryoglobulinemia, and
generalized pruritis.
(E) EBV is associated with nasopharyngeal carcinoma, oral hairy leukoplakia.
41. Cirrhosis can present with which of the following dermatologic symptoms?
A. Telangiectases
B. Transverse white bands on nails
C. White nail bed with sparing of the tip
D. All of the above
ANSWER: E.
EXPLANATIONS:
D. TRUE: All of these symptoms are associated with cirrhosis.
A. FALSE: Telangiectases, including spider angiomas, are commonly seen in patients with cirrhosis.
B. FALSE: Muehrcke’s nails (transverse white bands) are associated with cirrhosis.
C. FALSE: Terry’s nails (whitish nail beds sparing the tips) are associated with cirrhosis.
42. Which of the following clinical features, aside from age of onset, distinguishes adult-onset Still’s disease from
systemic-onset juvenile idiopathic arthritis?
A. Carpal ankylosis
B. Symmetric polyarthritis
C. Elevated serum ferritin
D. Asymptomatic transient skin eruption
E. Hepatomegaly
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Correct answer: (A) Carpal ankylosis.
Explanation: There are many similar features shared by both Still’s disease (systemic-onset juvenile idiopathic arthritis)
and adult-onset Still’s disease. Carpal ankylosis is a distinct feature of adult-onset Still’s disease and presents with
minimal pain but a limited range of motion in the carpal, proximal and distal interphalangeal joints. The
metacarpophlangeal joints are typically not involved. Both can present with arthralgias and an arthritis of multiple joints
affected symmetrically. In adult-onset Still’s disease, the joints affected are typically the knees wrists and ankles (Choice
B). Elevated acute phase reactants are mirrored between the two idiopathic rheumatologic diseases, and an elevated
serum ferritin is suggestive of a diagnosis in both. Similarly, each may demonstrate an elevated CRP, ESR, neutrophillia,
and thrombocytosis (Choice C). An asymptomatic transient skin eruption presenting with pink to erythematous macules
and papules that presents simultaneously with spiking fevers, is a feature shared by both clinical entities (Choice D).
Hepatomegaly is another feature seen in both SoJIA and adult-onset Still’s disease, and while splenomegaly is more
commonly seen in the former, it is less common in adult-onset Still’s disease. Involvement of the lungs, heart and kidneys
is also rare in adult-onset Still’s disease.
43. All of the following statements about anti-neutrophil cytoplasmic antibodies are True EXCEPT?
A. Autoantibodies to myeloperoxidase are more often found in Wegener’s Granulomatosis
B. Autoantibodies to myeloperoxidase are a feature of Microscopic Polyangitis
C. Autoantibodies that immunofluoresce around the periphery of a neutrophils nucleus are common
in Churg-Strauss syndrome
D. Autoantibodies that immunofluoresce in the cytoplasm of neutrophils are targeting proteinase-3
E. Elevated anti-neutrophil cytoplasmic antibodies can be demonstrated in inflammatory bowel
disease.
Correct answer: (A) Autoantibodies to myeloperoxidase are more often found in Wegener’s Granulomatosis.
Explanation: Autoantibodies to proteinase-3 or the cytoplasm-antineutrophil cytoplasmic antibodies (C-ANCA) are the
antibodies most often associated with Wegener’s Granulomatosis. Antibodies to myeloperoxidase, a perinuclear-ANCA is
more often found in Churg-Strauss Syndrome and Microscopic Polyangitis. The remaining choices are correct.
(B) Autoantibodies to myeloperoxidase (anti-MPO or P-ANCA) are a common feature of microscopic polyangitis.
(C) Autoantibodies that predominantly target the periphery of a neutrophils nucleus are know as peripheral anti-
neutrophil cytoplasmic antibodies, or P-ANCA, and target myeloperoxidase.
(D) Autoantibodies that predominantly target proteinase-3 will demonstrate strong immunofluorescence in the
cytoplasm of neutrophils and are known as cytoplasm-anti-neutrophil cytoplasmic antibodies, or C-ANCA.
(E) Elevated C and P-ANCA can be found in a number of non-dermatologic diseases including but not limited to Crohn’s
disease and ulcerative colitis. Additional conditions with elevated C/P-ANCA can include autoimmune hepatitis,
rheumatoid arthritis, mixed cyroglobulinemia, and infections such as hepatitis C and onchocerciasis.
44. Thyroid disease can be suspected by the dermatologist. Following are all skin findings associated with thyroid disease.
Which one is associated with hypothyroidism?
A. Warm skin
B. Hyperhidrosis
C. Soft skin
D. Hyperpigmentation
E. Edematous and boggy skin
Correct answer: (E) Edematous and boggy skin.

Explanation: Hypothyroidism is associated with dry, rough and coarse skin. The skin can also be cold and pale. Boggy and
edematous skin (myxedema) are also compatible features (the answer in this case). Easy bruising and a yellow
discoloration as a result of carotenemia are also found. In the case of hyperthyroidism, fine, velvety, smooth skin are
19
found. Warm and moist skin due to increased sweating (hyperhidrosis), as well as hyperpigmentation and pruritis can
also be found.
45. In lichen sclerosus, auto-antibodies against a specific target can be found, what is that target?
A. Extra-cellular matrix protein 1
B. Desmoglein 1
C. Histone
D. Double stranded DNA (dsDNA)
E. Collagen VII
Correct answer: (A) Extra-cellular matrix protein 1.

Explanation: Autoantibodies against extracellular matrix protein 1 (ECM-1) have been identified in the patient’s sera and
correlate with disease risk and activity.
Incorrect answers:
(B) Desmoglein-1 is a target in pemphigus foliaceus.
(C) Histone is a target in drug induced lupus erythematosus.
(D)Nephritic lupus is associated with anti-dsDNA auto-antibodies.
(E) Collagen VII is the target in epidermolysis bullosa acquisita.
46. Direct immunofluorescence of a skin biopsy from a patient with lesions of systemic lupus erythematosus is likely to
demonstrate which of the following features?
A. IgA deposition in the dermal papillae
B. IgG, IgM and C3 deposition around hair follicles
C. IgG, IgM and C3 deposition at the dermal epidermal junction and around hair follicles
D. IgG deposition surrounding keratinocytes in the epidermis
E. IgG and IgA deposition surrounding the vasculature of the superficial dermis
Correct answer: (C) IgG, IgM and C3 deposition at the dermal epidermal junction and around hair follicles.
Explanation: The lupus band, or granular deposition of IgG, IgM and C3 at both the dermal-epdidermal junction, as well
as around hair follicles is a consistent finding demonstrated on direct immunofluorescence in lesions of cutaneous lupus
erythematosus. It should be known, however, that while these findings can confirm the diagnosis of SLE, the absence of
them is not sufficient enough to rule SLE out.
(A) These findings are consistent with those seen in dermatitis herpetiformis.
(B) These findings are not sufficient to diagnose SLE alone, however in DIF studies done of tumid lupus, deposition at the
dermal-epidermal junction may not be present.
(D) These findings are those observed in pemphigus vulgaris.
(E) These findings are consistent with those observed in porphyria cutanea tarda.
47. A patient being treated with interferon for Hep C begins growing hair on his forehead. What should you check?
A. urine porphyrins
B. testosterone
C. 5 HIAA
D. AFP
Correct answer: (A) Urine porphyrins.

Explanation: Porphyria cutanea tarda (PCT) is the most common porphyia worldwide, and is due to a defect in
uroporphyrinogen decarboxylase (UROD). Numerous triggering factors and associations are known, including Hep C,
20
alcohol, estrogens, and HIV. Urinalysis should be conducted to confirm diagnosis. Elevated urinary excretion of
uroporphyrin is expected in PCT.
(B) PCT is not associated with testosterone aberrations.
(C) Urinary 5 HIAA analysis is helpful in diagnosis of carcinoid syndrome, not PCT.
(D) AFP monitoring is not indicated in the workup of PCT.
48. A patient presents to your clinic with a facial rash and proximal limb weakness. You suspect a diagnosis of
dermatomyositis and proceed to perform a full-body skin exam. Which of the following findings would NOT support
a presumed diagnosis of dermatomyositis?
A. Malar erythema
B. Nail fold telangiectasias
C. Erythematous papules involving the dorsum of the fingers
D. Poikiloderma on the lateral thighs
E. All of the above findings can support a diagnosis of dermatomyositis
Correct answer: (E) All of the above findings can support a diagnosis of dermatomyositis.
Explanation: All of the above cutaneous findings support a diagnosis of dermatomyositis.
(A) Malar erythema, which can be confused for the prototypical rash of systemic lupus erythematosus, is a common
finding in DM. However, this erythema tends to be more violaceous in hue with accompanying features of poikiloderma.
The facial rash of DM often involves the periorbital skin (heliotrope rash), and can present with or without significant
edema. Pruritus is a common feature of poikilodermatous skin in DM when the face is involved, and can help distinguish
the malar rash of DM from that of systemic lupus erythematosus.
(B) Nail fold telangiectasias along with fraying of the cuticles is often seen in dermatomyositis and along with the shawl
sign, violaceous poikiloderma around the neck in a photo-distribution, are common findings in juvenile and adult-onset
DM. However, capillary prominence of the nail fold can also be seen in other connective tissue diseases such as
scleroderma.
(C) Erythematous papules involving the dorsum of the fingers is a common finding in DM. Lichenification of the
erythematous papules over the joints of the fingers are called Gottron’s papules. Digital erythema may also be seen in
other connective tissue diseases such as systemic lupus erythematosus, but unlike the involvement seen in DM, this
erythema is not confined the flexor joints of the digits.
(D) Poikiloderma of the lateral thighs is known as the holster sign and is a cutaneous finding associated with DM.
49. A patient presents to your clinic with complaints of dry eyes, and a dry mouth giving her mucosa a gritty feeling. She
is concerned because of a family history of systemic lupus erythematosus and believes that these are symptoms.
Which of the following autoantibodies is most specific for Sjogren Syndrome?
A. SS-A
B. SS-B
C. Alpha-fodrin
D. dsDNA
Correct answer: (C) Alpha-fodrin.

Explanation: Anti-alpha fodrin autoantibodies are more specific for Sjogren Syndrome than both SS-A, also known as Ro
(Choice A), and SS-B (Choice B), also known as La, with a 60% and 20% prevalence respectively. Double-stranded DNA
(dsDNA, Choice D) is not a specific autoantibody for Sjogren Syndrome, but may be present in the case of overlap with
systemic lupus erythematosus, subacute cutaneous lupus erythematosus, and/or neonatal lupus.
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50. A patient presents with multiple skin and uterine leiomyomas. What is the associated cancer?
A. Renal cell carcinoma
B. Adrenal carcinoma
C. Colon adenocarcinoma
D. Pancreatic cancer
E. Ovarian cancer
Correct answer: (A) Renal cell carcinoma.

Explanation: Hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is an autosomal dominant familial cancer
syndrome that is characterized by cutaneous leiomyomas, uterine leiomyomas (fibroids), and renal cell cancer, as well as
rare reports of leiomyosarcoma. Renal cell cancer in HLRCC follows an aggressive clinical course and may be metastatic
at the time of initial diagnosis. Germline mutations in the fumarate hydratase (FH) gene predispose to HLRCC. FH
encodes an enzyme in the Krebs cycle that converts fumarate to malate. Patients with suspected HLRCC should be
screened for renal, uterine and skin tumors and offered genetic counseling and FH mutation testing. HLRCC surveillance
screening is continued throughout the lifetime of individuals at risk for HLRCC.
(B) Adrenal carcinomas are not associated with HLRCC.
(C) Colon adenocarcinomas are associated with Gardner’s syndrome and Muir-Torre syndrome.
(D) Pancreatic cancer is associated with necrolytic migratory erythema (glucagonoma syndrome).
(E) Ovarian cancer is associated with dermatomyositis.
51. In the POEMS syndrome, which skin finding(s) are you likely to encounter?
A. Rapid appearance of seborrheic keratosis
B. Glomeruloid hemangiomas, hypertrichosis and hyperpigmentation
C. Erosive disease of the mucosa
D. Large red to violet-brown patch
E. Concentric erythematous lesions, often giving the appearance of grains of wood
Correct answer: (B) Glomeruloid hemangiomas, hypertrichosis, and hyperpigmentation.

Explanation: Skin findings in the POEMS syndrome include: glomeruloid hemangiomas, cherry angiomas, sclerodermoid
changes, digital clubbing, hypertrichosis, and hyperpigmentation.
The POEMS acronym stands for (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes).
Osteosclerotic myeloma, Castleman’s disease, and plasmacytomas have been reported in patients with POEMS. The
rapid appearance of seborrheic keratosis is called the sign of Leser-Trélat and is controversial. It may be associated with
gastric carcinoma. Erosive disease of the mucosa is seen in paraneoplastic pemphigus. A large red to violet-brown patch
is seen in AESOP (adenopathy, extensive skin patch overlying (a) plasmacytoma). Concentric erythematous lesions, often
giving the appearance of grains of wood are the typical description of erythema gyratum repens, sometimes said to be
associated with pulmonary cancer.
52. Secondary extramammary Paget’s disease (EMPD) is most commonly associated with two underlying malignancies,
identify them in the following choices:
A. Lung and ovary cancer
B. Lung and gastric cancer
C. Colon and bladder cancer
D. Leukemia and plasma cell dyscrasia
E. Lymphoma and primary hepatocellular carcinoma
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Correct answer: (C) Colon and bladder cancer.
Explanation: It is well known that mammary Paget’s disease due to the epidermal extension of an underlying ductal
adenocarcinoma of the breast. Extramammary Paget’s disease (EMPD) represents a primary intraepithelial
adenocarcinoma in over 75% of patients. The two most common underlying malignancies causing secondary EMPD are
colon and bladder cancer.
Here is a non-exhaustive listing of cancer associations for the other answer choices: Lung cancer has many
manifestations such as acquired hypertrichosis lanuginosa but is not associated with EMPD.
For dermatomyositis, population-based studies demonstrate an over-representation of ovarian, lung, colorectal and
pancreatic carcinomas and non-Hodgkin lymphoma. Gastric cancer can be associated with acanthosis nigricans.
Leukemia and plasma cell dyscrasia are sometimes (10 to 20%) associated with neutrophilic dermatoses such as Sweet’s
syndrome and Pyoderma gangrenosum. Lymphoma has many associations such as exfoliative erythroderma, acquired
angioedema due to C1 esterase inhibitor dysfunction and acquired ichtyosis.
Primary hepatocellular carcinoma is known to be associated with porphyria cutanea tarda.
53. Which of the following statements regarding treatment of dermatomyositis is FALSE?

A. Early initiation of systemic corticosteroids while muscle enzymes are low can lead to rapid control
and occasionally resolution in 2-4 weeks
B. High potency topical steroids for cutaneous lesions of dermatomyositis are not effective in
treating associated pruritus
C. Systemic corticosteroids with a long and gradual taper can lead to an excellent prognosis in both
systemic and cutaneous symptoms of dermatomyositis
D. IVIg has demonstrated efficacy in recalcitrant disease in pediatric patients with dermatomyositis
Correct answer: (C) Systemic corticosteroids with a long and gradual taper can lead to an excellent prognosis in both
systemic and cutaneous symptoms of dermatomyositis.
Explanation: There is a distinct discordance in the success of treating the myopathy associated with dermatomyositis and
its cutaneous symptoms. Despite successful initiation of systemic and/or high potency topical corticosteroids with
significant resolution of myopathy, there exists a discrepancy in resolution of cutaneous involvement in both adult and
pediatric patients. Often, symptoms such as pruritus, associated with the cutaneous features of dermatomyositis do not
respond to either topical or systemic medications (Choice B). When initiated early in the disease process, systemic
corticosteroids with a gradual taper can bring the inflammation of the myopathy associated with DM under control
relatively quickly, however, this success is not seen with cutaneous lesions (Choice C). Steroid-sparing therapies are
gaining significant traction in both adult and pediatric patients with DM and can include pulse cyclophosphamide,
mycophenolate mofetil, infliximab, and in pediatric patients IVIg (Choice D).
54. Patients with juvenile dermatomyositis are at increased risk for?

A. Malignancy
B. Calcinosis
C. Interstitial lung disease
D. Cardiac disease
Correct answer: (B) Calcinosis.

Explanation: Juvenile dermatomyositis is more highly associated with calcinosis, and tends to favor sites of trauma.
(A) Dermatomyositis in adulthood is associated with malignancy, primarily colon and ovarian.
(C) Interstitial lung disease is primarily seen in adults and leads to fibrosis. Anti-Jo1 antibodies are associated with the
antisynthetase syndrome.
(D) Cardiac disease in dermatomyositis may present with conduction or rhythm disturbances, and is typically seen in
adults.
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55. A 33 year-old female returns to your clinic for discussions regarding positive lab findings including a positive double-
stranded DNA and positive anti-nuclear antibodies to a titer of 1:320. You explain how these findings support the
diagnosis discussed at her last visit. She begins to question a treatment approach, and in particular is concerned
about preventing exacerbation of both her cutaneous and systemic symptoms. Which of the following modalities can
prevent exacerbation of both cutaneous and systemic disease?
A. Topical corticosteroids
B. Systemic corticosteroids
C. Sun-protection with physical sunblock
D. Systemic retinoids
Correct answer: (C) Sun-protection with physical sunblock.

Explanation: The mainstay of preventing exacerbation of both cutaneous and systemic features of systemic lupus
erythematosus, the diagnosis of the patient in question supported by the aforementioned lab findings, remains sunblock
with physical blockers such as zinc and titanium oxide. These, in addition to chemical sunblock, sun-protective clothing,
and sun avoidance, can all prevent the development, and worsening of cutaneous lesions of SLE as well as systemic
symptoms, demonstrating a role of ultraviolet light in both the onset and continuation of the disease. While topical and
systemic medications can improve cutaneous and systemic findings, as well as prevent onset and exacerbation, there is
little evidence supporting the preventative nature of the therapeutic modalities in choices A-B and D. High potency
topical steroids can certainly lead to the resolution of cutaneous features of SLE, but cannot prevent their occurrence.
Similarly the use of systemic therapy such as retinoids and systemic corticosteroids, is less likely to serve a therapeutic
role in the treatment of cutaneous lesions in contrast to systemic signs and symptoms associated with SLE.
56. Which of the following immunofluorescent patterns is incorrectly paired with its substrate?
A. Peripheral rim pattern and double-stranded DNA (dsDNA)
B. Homogenous pattern and topoisomerase
C. Nucleolar pattern and fibrillarin
D. Speckled pattern and ribonculeoproteins
E. Centromeric pattern and chromosomal centromeres
Correct Answer: B. Homogenous pattern and topoisomerase.

Explanation: The homogenous pattern of immunofluorescence corresponds with either double-stranded DNA, which has
95% specificity for systemic lupus erythematosus (SLE), or anti-histone antibodies that are most indicative of drug-
induced lupus. Topoisomerase targeting by immunofluorescence represents a speckled anti-RNP staining pattern that is
found in 95% of patients with scleroderma.
Incorrect Answers:
A. The peripheral rim pattern corresponds to dsDNA.
C. The nucleolar pattern corresponds to binding of ribosomal RNA processing molecules such as fibrillarin and
topoisomerase.
D. The speckled pattern is due to immunofluorescent targeting of a number of nuclear proteins and ribonuclear proteins
including Smith, U1RNP, Ro and La.
E. The centromeric pattern, or discrete speckled pattern, results from antibody binding to the polypeptide components of
chromosomal centromeres.
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57. Cutaneous manifestations of hepatitis C include all of the following, except?
A. Porphyria cutanea tarda (PCT)
B. Lichen planus
C. Small vessel vasculitis
D. Xanthomas
E. Necrolytic acral erythema
Correct answer: (D) Xanthomas.

Explanation: Xanthomas are not associated with Hepatitis C. They are seen in association with primary biliary cirrhosis.
(A) PCT is associated with hepatitis C and hepatitis B.
(B) LP, especially erosive oral disease, is associated with hepatitis C.
(C) LCV is associated with hepatitis C.
(E) Necrolytic acral erythema is associated with hepatitis C.
58. All of the following statements regarding relapsing polychondritis are true EXCEPT?
A. Auricle chondritis is more recurrent then nasal chondritis
B. Men and women are equally affected
C. Erythema and pain of the auricle is a prominent feature
D. It is an auto-immune disease with a positive association with HLA-DR4
E. Circulating antibodies to collagen type II must be present for the diagnosis
Correct answer: (E) Circulating antibodies to collagen type II must be present for the diagnosis.
Explanation: Statements A–D are all correct regarding relapsing polychondritis (RPC). Nasal chondritis, which can lead to
a saddle nose deformity, affects up to 70% of patients as opposed to the 90% of patients with RPC who develop auricular
involvement that can be recurrent. Men and women are equally affected which is typically not the case as most auto-
immune disease has a female predominance. Erythema, pain, swelling and scarring of the auricle is a prominent feature
in RPC. Like other auto-immune diseases RPC has a positive association with a specific human leukocyte antigen, and in
this disease it is HLA-DR4. The pathogenic basis for RPC is an immunologic reaction against Type II Collagen, however,
circulating antibodies against this form of collagen, which is the main component of cartilage, is only present in about
half of the affected patients (Choice A).
59. A patient presents with chronic urticaria, fever, bone pain, athralgias and myalgias. Which underlying systemic
association must be ruled out?
A. IgG kappa gammopathy
B. IgG lambda gammopathy
C. IgM gammopathy
D. None of the above
Correct answer: (C) IgM gammopathy.

Explanation: Chronic urticaria along with fever, bone pain, athralgias, and myalgias suggests Schnitzler’s syndrome,
which is associated with monoclonal immunoglobulin M (IgM) gammopathy.
(A) IgG kappa gammopathy is associated with scleredema and necrobiotic xanthogranuloma.
(B) IgG lambda gammopathy is associated with scleromyxedema.
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60. Which of the following symptoms is a Major criterion in the diagnosis of Beçet’s Disease?
A. Pathergy
B. Posterior Uveitis
C. Oral Aphthous Ulcers
D. Anterior Uveitis
E. Deep Venous Thrombosis
Correct answer: (C) Oral Aphthous Ulcers.

Explanation: According to the International Study Group for Behçet’s Disease, recurrent aphthous oral ulceration is the
sole Major criterion in the diagnosis of the disease. Genital ulcers are concomitantly seen along with the development of
oral ulceration, however this is considered minor criteria. In men the ulceration predominantly involves the base of the
penis or scrotum, while in women ulceration affects the vulva. Minor criteria include eye involvement with posterior
uveitis being the most common ocular symptom. Anterior uveitis may occur, but with far less frequency compared to
posterior uveitis. Skin findings including pathergy (or the development of pyoderma like lesions following trauma, often
from intravenous needle sticks or blood draws) is one of several cutaneous findings commonly found in patients with the
disease. Other skin findings that make up minor criteria include acneiform eruptions, papulopustular lesions, erythema
nodosum-like lesions, furuncles, abscesses, papules, vesicles, pustules and purpura. Aneurysmal and thromboembolic
disease such as deep vein thrombosis are not part of the diagnostic criteria, however, it is a common cause of mortality
in children along with intestinal perforation, neurologic involvement, and complications secondary to medical
management of Beçet Disease.
61. While reviewing the pathology report for a patient you have been following for a new-onset mid-facial rash that
became more apparent following sun-exposure, you realize that the second page of the report is missing. The
pathology states that the diagnosis was consistent with lupus erythematosus, but further classification, which would
normally be on the second page, is not available. Biopsy of the malar rash would most likely present with
inflammation involving which of the following?
A. Epidermis and superficial dermis only
B. Epidermis only
C. Epidermis, superficial and deep dermis, as well as adnexal involvement
D. Dermis only
E. Dermis and subcutaneous fat
Correct answer: (A) Epidermis and superficial dermis only.

Explanation: The vignette in question describes a patient who had received a biopsy of the classic photosensitive malar
rash found in acute cutaneous lupus erythematosus. Classification of SLE is primarily dependent on the location of the
associated inflammation on histopathologic examination. On pathology, the inflammatory infiltrate associated with the
malar rash of acute LE is located primarily at the junction between the epidermis and dermis, with extension not going
beyond the superficial dermis. All forms of lupus erythematosus involve varying degrees of skin depth which is noted by
the presence of an inflammatory infiltrate on histopathology, however, there are no variants of lupus that involve only
the epidermis (Choice B). Discoid lupus lesions, in which the inflammatory infiltrate extends from the dermal-epidermal
junction to the deep dermis while also involving the adnexa (Choice C), is a chronic cutaneous variant of sub-acute
cutaneous lupus erythematosus (SCLE). Like SCLE, discoid lesions as part of discoid lupus erythematosus (DLE) or as part
of SLE, have a higher propensity of scarring because of the depth of the inflammatory infiltrate and involvement of the
adnexa. Lesions of acute lupus erythematosus such as the malar rash, have no significant risk of scarring giving the
superficial involvement of the inflammatory infiltrate seen on pathology. Lesions of tumid lupus, a possibly intermediate
form of cutaneous lupus erythematosus, have an inflammatory infiltrate occupying predominantly the dermis only
(Choice D), while lesions of lupus profundus (or lupus panniculitis) are characterized by an inflammatory infiltrate
primarily in the deep dermis with a majority present within the subcutaneous fat.
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62. A newborn can be affected by lupus. Neonatal subacute lupus erythematosus is caused by one of the following
scenarios, which one is the most probable?
A. The newborn’s auto-immune system is synthetizing anti-Ro auto-antibodies.
B. The newborn was exposed to UV rays to treat is kernicterus and started to synthetize anti-La
antibodies.
C. The mother has taken methyldopa during pregnancy to control high blood pressure and
transferred to her fetus anti-histone auto-antibodies to her newborn during pregnancy.
D. The mother has subacute cutaneous lupus erythematosus her self and has transferred anti-Ro
auto-antibodies to her fetus during pregnancy.
E. The newborn had sun exposure without propre protection and the ultraviolet radiations caused
damage that exposed skin antigens and that triggered the disease.
Correct answer: (D) The mother has subacute cutaneous lupus erythematosus her self and has transferred anti-Ro
auto-antibodies to her fetus during pregnancy.
Explanation: A mother with subacute lupus erythematosus can transfer her anti-Ro auto-antibodies to her fetus during
pregnancy. The newborn can be born with skin lesions or can develop them after birth. Close to 100% of babies with
neonatal lupus erythematosus (NLE) have anti-Ro antibodies. Photosensitivity is very common in NLE but sun-exposure is
not required for NLE lesions to appear as it is possible for the lesions to be present at birth. All other scenarios are
erroneous and are not known to cause NLE. The typical lesions have a predilection for the face, especially the periorbital
region and scalp. They resolve without scarring, although dyspigmentation may persist for many months, and some
children have residual telangiectasias. The major extracutaneous findings include a congenital heart block (accompanied
by cardiomyopathy or not), hepatobiliary disease and thrombocytopenia. Therefore, the monitoring of platelets, liver
enzymes and heart with an electrocardiogram are mandatory if a child is diagnosed with NLE.
63. A 32 year-old male presents to your clinic complaining of intense burning and pain with associated redness of the ear,
and denies any history of trauma. A physical exam of the ears demonstrates tender erythema with sparing of the ear
lobes. You discuss with your patient what you believe is the diagnosis, and he is concerned about serious
complications both short and long term. Which of the following is the most serious complication of your diagnosis?
A. Saddle nose deformity

B. Compromised hearing
C. Respiratory tract compromise
D. Arthritis
E. Ocular inflammation
Correct answer: (C) Respiratory tract compromise.

Explanation: Involvement of the respiratory tract cartilage, with or without costochondral joint involvement is the most
serious complication of relapsing polychondritis (RPC). An inflammatory attack on collagen type II will involve the
respiratory tract in 50% of patients. Signs of involvement include choking, cough, dyspnea, hoarseness, wheezing or
tenderness to the anterior aspect of the neck at the site of the larynx or trachea. Potentially serious outcomes such as
airway obstruction or collapse should be frequently screened for in these patients.
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(A) Nasal cartilage inflammation is present in up to 70% of patients with RPC, and can lead to saddle nose deformity.
Signs of nasal cartilage involvement include rhinorrhea, crusting, congestion, pain, and epistaxis. Long term
complications may lead to decreases sensation in smell and deformity.
(B) Inflammation of the auricle can lead to significant swelling and this may approach the external auditory meatus
causing compromised hearing.
(D) Arthritis is present in 50-80% of patients with RPC and presents as a non-symmetric, non-erosive arthritis of multiple
joints, often affecting the MCP, PIP, and knees. Cartilaginous areas of the chest wall can also be affected such as the
sternoclavicular and sternomanubrial joints.
(E) Ocular inflammation is common and present in up to 65% of RPC patients. The inflammation can involve all anatomic
parts of the eye leading to optic neuritis, conjunctivitis, uveitis, and corneal ulcerations.
64. A patient with positive perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) presents the following signs and
symptoms: palpable purpura, subcutaneous nodules, allergic rhinitis with bloody nasal discharge, acute hearing loss,
asthma and glomerulonephritis with hematuria. Eosinophilia is also revealed on blood tests. Which of the following
diagnosis is most probable?
A. Granulomatosis with polyangiitis
B. Eosinophilic granulomatosis with polyangiitis
C. Cutaneous small vessel vasculitis caused by a viral infection
D. Microscopic polyangiitis
E. Polyarteritis nodosa
Correct answer: (B)

Explanation: The illustrated scenario is one of vasculitis. Since there are subcutaneous nodules and a positive P-ANCA,
the diagnosis is oriented towards a small to medium size vessels vasculitis. Eosinophilic granulomatosis with polyangiitis,
previously known as Churg-Strauss syndrome, is a P-ANCA positive vasculitis in which the following signs and symptoms
can be found: allergic rhinitis, nasal polyps, asthma, eosinophilic pneumonia, myocarditis, coronary arteritis, eosinophilic
gastroenteritis, ischemia, glomerulonephritis, mononeuritis multiplex, palpable purpura, subcutaneous nodules.
The sinus computed tomography reveals paranasal sinus abnormality. The chest computed tomography shows non-fixed
infiltrate. Urinalysis can show hematuria or red blood cell casts. Complete blood count/differential demonstrates an
eosinophilia > 10%. The skin biopsy will have the following features: extravascular eosinophils, granulomatous
inflammation, vasculitis of small-to medium-sized vessels.
Microscopic polyangiitis includes the following signs and symptoms: alveolar capillaritis and/or hemorrhage, no asthma,
a necrotizing glomerulonephritis, palpable purpura, hematuria, small vessel vasculitis but no granulomas.
Granulomatosis with polyangiitis (Wegener’s granulomatosis) is C-ANCA positive and not P-ANCA positive and includes
the following signs and symptoms: rhinitis, ulceration with bloody nasal discharge or crusting for >1 month, septal
perforation or saddle nose, otitis media, acute hearing loss, hypertrophic gingivitis, subglottic stenosis, proptosis,
scleritis, cough, dyspnea, chest pain, glomerulonephritis, palpable purpura, subcutaneous nodules, ulcers. A diagnosis of
granulomatosis with polyangiitis is supported by a sinus computed tomography showing chronic sinusitis, otitis and/or
mastoiditis, the destruction of bone/cartilage. It can also be demonstrated if a chest computed tomography shows:
nodules, fixed infiltrates or cavities. A urinalysis with hematuria or red blood cell casts is also in favor of granulomatosis
with polyangiitis. The skin biopsy will show granulomatous inflammation. The biopsy will reveal vasculitis of small- to
medium-sized vessels.
A cutaneous small vessel vasculitis caused by a viral infection is not P-ANCA positive and would mostly present with
palpable purpura but not subcutaneous nodules, a hearing loss, asthma or allergic rhinitis with a bloody discharge.
Polyarteritis nodosa is not the most probable diagnosis because it is not P-ANCA positive and usually presents with livedo
racemosa, retiform purpura, ulcers, subcutaneous nodules and digital necrosis.
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65. Which of the following cutaneous features of relapsing polychondritis is indicative of an associated myelodysplastic
syndrome?
A. Aphthous ulcers
B. Cutaneous small vessel vasculitis
C. Livedo reticularis
D. Choices A and B
E. All of the above
Correct answer: (D) Choices A and B.

Explanation: There are several non-specific cutaneous findings often present in patients with relapsing polychondritis
(RPC). These reactive lesions include oral aphthous ulcers, small vessel vasculitis, annular urticarial plaques, livedo
reticularis, erythema elevatum diutinum and erythema nodosum. However, the presence of either cutaneous small vessel
vasculitis and/or aphthous ulcers should alert the physician to the potential association of RPC with a myelodysplastic
syndrome. It is also important to remember the MAGIC syndrome, which is an acronym that stands for mouth and
genital ulceration with inflamed cartilage.
66. Renal disease associated with a skin disase is not uncommon. Which of the following skin disease is associated with
the increased risk of having congenital nephrosis and glomerulonephritis?
Tuberous sclerosis
Fabry disease
Nail-Patella syndrome
Birt-Hogg-Dubé syndrome
Familial cutaneous leiomyomatosis
Correct answer: (C) Nail-Patella syndrome.

Explanation: Nail-Patella syndrome has the following features: hypoplasia of the nails, with greatest involvement of
thumb and lateral digits and a triangular lunulae (mostly found on the thumbs). It can present with renal anomalies such
as congenital nephrosis and glomerulonephritis. It is autosomal dominant and due to a mutation in LMX1B.
Fabry disease also has renal involvement but it results in proteinuria and renal failure due to accumulation of ceramide
trihexoside.
Tuberous sclerosis has many features and can express itself by renal hamartomas (angiomyolipomas). Polycystic kidney
disease may occur in a contiguous gene syndrome with TSC2. CNS tumors, intellectual disability, cardiac rhabdomyomas
and seizures are also possible findings. It is autosomal-dominant and caused by mutations in TSC1 or TSC2, encoding
hamartin and tuberin.
Birt-Hogg-Dubé syndrome is known for the classic triad of fibrofolliculomas, trichodiscomas and acrochordons. Renal
tumors are the following : chromophobe and hybrid oncocytic carcinomas. Birt-Hogg-Dubé is important to diagnose early
because of the risk for spontaneous pneumothoraces. It is caused by mutations in the gene encoding folliculin (FLCN).
Familial cutaneous leiomyomatosis presents with multiple cutaneous leiomyomas. It predisposes the patient to develop
renal carcinoma. Uterine leiomyomas are a common feature and the disease is due to mutations in the gene encoding
fumarate hydratase.
67. All of the following are diagnostic criteria for systemic-onset juvenile idiopathic arthritis (Still’s Disease) EXCEPT?
A. Elevated episodic fevers for greater than 2 weeks
B. The presence of rheumatoid nodules
C. Symmetric polyarthritis
D. The presence of an evanescent cutaneous eruption
E. All of the above
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Correct answer: (B) The presence of rheumatoid nodules.
Explanation: Rheumatoid nodules are not common findings in patients with systemic-onset juvenile idiopathic arthritis
(SoJIA). While they are rarely present in these patients, they are not common enough to be considered part of the
diagnostic criteria. At least one of the following is considered a feature required for diagnosis; the evanescent eruption
(Choice D), generalized lymphadenopathy, hepatomegaly, splenomegaly, or serositis. One of these findings must be
accompanied by high episodic fevers for greater than 2 weeks (Choice A) and a symmetric polyarthritis (Choice C).
68. Mucin deposition is a characteristic feature of all the following conditions, except?
A. Scleromyxedema
B. Scleredema
C. Scleroderma
D. Reticulated erythematous mucinosis
E. All of the above
Correct answer: (C) Scleroderma.

Explanation: Mucin accumulation is not a key histologic feature of scleroderma.
(A) Scleromyxedema clinically presents with firm, indurated, waxy papules. This condition is associated with a triad of
microscopic features: mucin deposition, increased collagen deposition, and a proliferation of fibroblasts.
(B) Scleredema presents with symmetric induration of the upper back, chest, and shoulders. Mucin accumulation in the
reticular dermis is a characteristic feature.
(D) Reticulated erythematous mucinosis (REM) presents with erythematous, photoexacerbated plaques on the upper
chest. Interstitial mucin deposition in the upper dermis is notable for REM.
69. A patient you have been following for a few years for dermatomyositis was recently hospitalized for significant
respiratory distress. At your visit with her while rounding, you examine the notable hand swelling and cutaneous
ulcerations she has always suffered from since her initial diagnosis. After discussing her case with the radiologist, you
learn that her lung disease has rapidly progressed dramatically reducing her ability to function without assistance.
Which of the following autoantibodies is responsible for this clinical presentation of dermatomyositis?
Correct answer: (E) Anti-MDA5/CADM-140 autoantibodies.

Explanation: Anti-MDA5/CADM-140 autoantibodies are associated with a distinct clinical phenotype in patients with
with an increased mortality secondary to rapidly progressive interstitial lung disease. The prevalence of these
autoantibodies parallels that of anti-Mi2 and Jo1 autoantibodies, but is higher than anti-SRP autoantibodies.
(A) In one study, 80% of adult patients with amyopathic (no skeletal muscle involvement) dermatomyositis,
papules, Gottron’s sign, the shawl sign (violaceous poikiloderma around the neck) and frayed cuticles. This autoantibody
does not increase the risk of internal malignancy.
30
Patients with these autoantibodies are often defined as having the antisynthetase syndrome. The prevalence of anti-Jo1
autoantibodies is relatively low. Patients with them, however, are more prone to developing arthritis, Raynaud’s
phenomenon, and interstitial lung disease. Mortality is more often due to interstitial lung disease, however in this subset
of DM patients, the lung disease is not as rapidly progressive as is demonstrated in the anti-MDA5/CADM140 patients.
(D) Anti-SRP (signal recognition particle) autoantibodies are associated with fulminant dermatomyositis with an
increased mortality rate secondary to cardiac involvement. Prevalence of these autoantibodies is lower then anti-Mi2
and anti-Jo1 autoantibodies.
70. In patients with anti-U1RNP positive mixed connective tissue disease, what is the most common cause of mortality?
A. Pulmonary hypertension
B. Pulmonary fibrosis
C. Pleuritis
D. Pericarditis
E. Progressive systemic sclerosis
Correct answer: (A) Pulmonary hypertension.

Explanation: Mixed connective tissue disease (MCTD) is an important clinical entity for the dermatologist to be aware
because as is implied by its name, it often has features of overlap between systemic sclerosis (Scleroderma),
dermatomyositis (inflammatory myopathy) and both cutaneous and systemic involvement akin to that of systemic lupus
erythematosus. By and far the leading cause of mortality in patients with MCTD is pulmonary hypertension. This occurs
in up to 25% of patients with a diagnosis of MCTD and is associated with anti-phospholipid antibodies. It has an insidious
and sub-clinical onset, and patients with a diagnosis of MCTD should be frequently assessed for its presence. Similarly,
pulmonary fibrosis (Choice B) also has a subclinical and insidious onset, but tends to be mild and asymptomatic. Pleurisy
and pericarditis (Choices C and D) are common findings in patients with MCTD, similar to that seen in systemic lupus, and
have a prevalence of 60% in these patients. They do not however, significantly contribute to overall mortality. Cutaneous
sclerosis (Choice E), similar in presentation to scleroderma, can be seen in patients with MCTD and is typically confined to
the distal extremities. Sclerosis of the trunk, proximal extremities, neck and face is not common feature of MCTD and can
be used to distinguish it from progressive systemic sclerosis.
71. Dermatomyositis has many presentations. The amyopathic form presenting with rapidly progressive interstitial lung
disease is associated with an antibody targeting which of the following choices?
A. SRP
B. MDA5/CADM-140
C. Jo-1
D. Mi-2
E. p155
Correct answer: (B) MDA5/CADM-140.

Explanation: All of the listed choices are associated with certain forms of presentation of dermatomyositis (DM). The
amyopathic form presenting with rapidly progressive interstitial lung disease is associated with antibodies targeting
MDA5/CADM-140. Other forms are associated with other targets such as:
- Antisynthetase syndrome associated with anti-Jo-1, anti-PL-7, anti-PL12, anti-OJ, anti-EJ antibodies
- Clinically amyopathic DM, adult onset DM and an increased risk in malignancy are all associated with anti-p155
antibodies
- Fulminant DM is associated with anti-SRP antibodies
31
- Gottron’s papules/sign, shawl sign, periungual telangiectasias, cuticular overgrowth/dystrophy are associated with
anti-Mi-2 antibodies.
72. Which of the following cutaneous manifestations of rheumatoid arthritis warrants peripheral nerve study work-up to
rule out neuropathy?
A. Non-healing lower extremity ulcers of Felty Syndrome
B. Palpable purpura associated with rheumatoid vasculitis
C. Nailfold thromboses of Bywater’s lesions
D. Tender truncal plaques of Sweet’s Syndrome
E. Lower extremity ulceration associated with pyoderma gangrenosum
Correct answer: (B) Palpable purpura associated with rheumatoid vasculitis.

Explanation: All of the above clinical findings are often seen in patients with rheumatoid arthritis. The presence of
rheumatoid nodules represents only one common cutaneous presentation of RA, a multitude of other skin findings are
seen at varying rates in patients with RA, emphasizing the role dermatologists play in treating this disease. Rheumatoid
vasculitis can affect both small and medium sized vessels, and depending on the size of vessel affected, clinical
presentation can vary from palpable purpura (Choice B) to livedo reticularis and digital infarcts. Systemic findings
associated with rheumatoid vasculitis include cerebral infarction, scleritis, intestinal ulcers, proteinurea, and
neuropathies. In up to 40% of patients with medium-sized vessel rheumatoid vasculitis, there are clinic signs and
symptoms of peripheral neuropathy. This often presents as mononeuritis multiplex and is common enough that in
patients without histological evidence of rheumatoid vasculitis after serial biopsy, but still present with cutaneous signs
of vasculitis, nerve conduction studies are warranted.
(A) Felty syndrome, which is composed of granulocytopenia, splenomegaly, and persistent leg ulcers increases the risk of
cutaneous and systemic infections refractory to treatment in patients with RA, but does not predispose them to
peripheral neuropathy.
(C) Bywater’s lesions include Purpuric papules on the volar aspect of the digital pulp and nailfold thromboses. These
lesions present with a small vessel vasculitis that differs from rheumatoid vasculitis and is not associated with peripheral
neuropathy.
(D) (E) Sweet’s syndrome and pyoderma gangrenosum are neutrophillic dermatoses that can present frequently in
patients with RA. They do so at a higher rate when compared to the general population. Neither of these cutaneous
features is associated with peripheral neuropathy. Bullous or atypical sweets, as well as numerous abdominal or facial
lesions of pyoderma gangrenosum warrant additional work up for not only rheumatologic disease, but also underling
hematologic malignancy and myelodysplastic disease.
73. A patient is referred to you by his primary care physician for definitive diagnosis. He was initially seen for renal
disease and later demonstrated discoid lesions on the scalp, but denies the presence of a malar rash, or any associated
photosensitive eruptions. To confirm your suspicion of lupus, you submit a request for lab studies. Autoantibodies to
which of the following are most specific for systemic lupus erythematosus (SLE)?
A. double-stranded DNA (dsDNA)
B. single-stranded DNA (ssDNA)
C. Ro
D. La
E. Histones
Correct answer: (A) Double-stranded DNA (dsDNA).

Explanation: The prevalence and specificity of both Smith (Sm) antigen as well as dsDNA are high enough that
autoantibodies to either of these are considered one of the eleven classification criteria established by the American
College of Rheumatology for the diagnosis of SLE.
32
(B) Autoantibodies to single-stranded DNA can also be seen in SLE but are not specific to this connective tissue disease.
(C) (D) Both Ro (SS-A) and La (SS-B) are human cytoplasmic ribonuclear proteins found in the cytoplasm and nucleus of
cells. Autoantibodies to these proteins are not specific to SLE. They are more commonly associated with subacute
cutaneous lupus erythematosus (SCLE), neonatal lupus, SCLE-Sjogren's syndrome overlap, primary Steven Johnson
syndrome, and other mixed connective tissue diseases.
(E) Anti-histone antibodies are more commonly associated with drug-induced SLE, rheumatoid arthritis, and systemic
sclerosis with pulmonary fibrosis (in conjunction with additional autoantibodies).
74. Rheumatoid arthritis (RA) can be treated with a wide variety of drugs.If a patient suffering from RA develops drug-
induced pemphigus foliaceus, which of the following drugs is most likely to be the cause?
A. Infliximab
B. Methotrexate
C. Gold
D. Penicillamine
E. Naproxen
Correct Answer: D. Penicillamine.

Explanation: Drug-induced illnesses are important to recognize. Many presentations are classic and should be known to
the keen dermatologist. Penicillamine is one of these. It is a well-known inducer of drug-induced pemphigus.
Other diseases it can induce are: lichenoid drug reaction, elastosis perforans serpiginosa and pseudoxanthoma
elasticum-like changes.
Incorrect Answers:
A. Infliximab is a tumor necrosis factor inhibitor and can cause a wide variety of effects such as: local injection site
reaction, urticaria, angioedema, anaphylaxis, vasculitis (small or larger vessel vasculitis, interstitial granulomatous
dermatitis, lupus erythematosus – systemic or cutaneous, new-onset psoriasiform eruption and palmoplantar pustulosis
accelerated nodulosis as well as dermatomyositis.
B. Methotrexate can be the cause of accelerated nodulosis (most often on the hands) as well as the methotrexate-
induced papular eruption that favors the extremities.
C. Gold can induce a pityriasis rosea-like eruption as well as lichenoid drug reactions. It can actually be used as a
treatment for pemphigus vulgaris, and, oddly enough, can even sometimes be implicated (although rarely) as a cause.
The use of gold treatment is mainly historical at this point.
E. Non-steroidal anti-inflammatory drugs (NSAIDs) (such as naproxen in this question) are associated with
pseudoporphyria and toxic epidermal necrolysis (TEN).
75. A patient with lupus is not responding to Plaquenil. Which of the following is a likely contributing factor?
A. smoking
B. grapefruit juice
C. ketoconazole
D. erythromycin
E. cimetidine
Correct answer: (A) Smoking.

Explanation: Hydroxychloroquine has been used for decades as a mainstay of systemic therapy for lupus. Smoking has
been associated with decreased efficacy of antimalarials. The exact mechanism is unknown.
(B) Grapefruit juice does not affect Plaquenil efficacy.
(C) Ketoconazole- Ketoconazole is a CYP3A4 inhibitor. Plaquenil is predominantly metabolized by CYP2D6, therefore
ketoconazole does not affect Plaquenil metabolism nor efficacy.
33
(D) Erythromycin is a CYP3A4 inhibitor. Plaquenil is predominantly metabolized by CYP2D6, therefore ketoconazole does
not affect Plaquenil metabolism nor efficacy.
(E) Cimetidine actually increases circulating levels of antimalarials by preventing its metabolism. As such, decreased
efficacy would not be expected.
76. Which of the following regarding this condition is false?
A. more commonly seen in men

B. may be associated with diabetes and
thyroid disease
C. spontaneous resolution is expected in
localized disease
D. histologically, a palisading granuloma is seen
with necrobiosis and mucin deposition
E. none of the above
Correct answer: (A) More commonly seen in men.

Explanation: Granuloma annulare (GA) is a common idiopathic skin condition, which presents with non-scaly annular
plaques and erythematous papules, most common on hands, feet, and elbows. It is most commonly seen in children and
young adults, with a female predominance.
(B) GA may be associated with diabetes and thryoid disease.
(C) Localized variants of GA are expected to clear spontaneously.
(D) Histologically, palisading granulomas are seen with histiocytes and giant cells surrounding foci of necrobiosis
(connective tissue degeneration) and mucin deposition.
77. A patient presents to your clinic 2 weeks following her Florida vacation with a distinctly annular scaly rash on the
back and lateral aspects of her arms. This is the first time she has experienced this rash and had seen a clinician while
on vacation who submitted labs but referred her case when an ANA came back positive but a double-stranded DNA
came back negative. Which of the following lab exams would most likely confirm your diagnosis?
A. Autoantibodies to single-stranded DNA
B. Autoantibodies to Mi-2
C. Autoantibodies to Ro
D. Autoantibodies to La
E. None of the above lab exams would be expected to be positive in this patient
Correct answer: (C) Autoantibodies to Ro.

Explanation: Up to 70% of patients with subacute cutaneous lupus erythematosus (SCLE), with a range of 60-100% in
some studies, demonstrate anti-Ro antibodies. This is the most frequently encountered autoantibody in SCLE, but it can
also be present in patients with Sjogren’s Syndrome. Not coincidentally, patients with SCLE may have symptoms of
Sjogren’s Syndrome.
(A) Autoantibodies to ssDNA can be present in patients with SCLE, but are more often associated with systemic lupus.
(B) Autoantibodies to Mi2 are not seen in patients with SCLE, but are present in some forms of dermatomyositis.
(D) Autoantibodies to La are commonly found in patients with SCLE, however, their prevalence is not as strongly
correlated to SCLE and are often seen in many of the overlap syndromes.
(E) Autoantibodies to Ro, La, U1RNP, histones, and ssDNA may all be present in patients with systemic lupus, but alone,
none are disease-specific.
34
78. You are consulted on an in-patient who was admitted for the rapid and sudden onset of numerous skin colored, non-
tender, nodules involving the upper and lower extremities. His hospitalization was initially for the intravenous
medication that was being given to treat his rheumatoid arthritis (RA). Which of the following medications is most
likely associated with his cutaneous findings?
A. Naproxen
B. Intralesional corticosteroids
C. Cyclosporine
D. Rituximab
E. Infliximab
Correct answer: (E) Infliximab.

Explanation: Rapid accelerated nodulosis, the diagnosis of the patient in this vignette, has been reported to occur
following the initiation of several medications often used to treat rheumatoid arthritis (RA). The initiation of
methotrexate, and tumor necrosis factor alpha inhibitors such as infliximab, has demonstrated causality in rapid
accelerated nodulosis in patients with RA. Additionally, there have been several reports linking rapid tapering of
systemic corticosteroids to a similar clinical picture. While choices A-D are frequently used in the treatment of RA,
evidence suggesting that they are correlated to rapid onset nodulosis is not supported.
79. Lupus erythematosus has many forms of presentation. You are examining skin biopsies taken from a patient and
identify the following histopathological findings: hyperkeratosis, follicular plugging, pilosebaceous atrophy, basement
membrane thickening and periadnexal lymphocytic infiltrate. Which subtype is the most probable diagnosis?
A. Acute cutaneous lupus erythematosus
B. Subacute cutaneous lupus erythematosus
C. Discoid lesions of lupus erythematosus
D. Lupus erythematosus tumidus
E. Lupus panniculitis
Correct answer: (C) Discoid lesions of lupus erythematosus.

Explanation: Discoid lesions of lupus erythematosus have the following histopathological characteristics: pilosebaceous
atrophy, follicular plugging, basement membrane zone thickening, lymphocytic infiltrate in the upper dermis and in the
lower dermis. The lymphocytic infiltrate will be periadnexal. In contrast, acute cutaneous lupus erythematosus will not
demonstrate hyperkeratosis, nor follicular plugging or pilosebaceous atrophy. The lymphocyte infiltrate will only be in
the upper dermis and will not be periadnexal. The findings will be similar as in acute cutaneous lupus erythematosus in
subacute cutaneous lupus erythematosus, except that the lymphocyte infiltrate can sometimes be periadnexal and
follicular plugging is possible, but not as important as in the discoid variant. Lupus erythematosus tumidus doesn’t
involve the adnexa. Lupus panniculitis involves mainly the subcutis, and therefore has an important lymphocytic infiltrate
in the subcutis, which is not the main clinical picture depicted in the scenario.
80. One of the patients you have been following for psoriasis presents to your clinic with the onset of a new facial rash,
fevers, and laboratory evidence of thrombocytopenia and leukopenia. You suspect drug-induced lupus, but begin to
consider alternative diagnoses when his lab report returned positive for ANA (with a titer of 1:160), negative for anti-
histone antibodies, and positive for autoantibodies to double-stranded DNA. The most likely cause of these lab
findings is which of the following?
A. Hydralazine
B. Minocycline
C. Etanercept
D. Procainamide
E. Ustekinumab
35
Correct answer: (C) Etanercept.
Explanation: Several of the biologics used to treat psoriasis, psoriatic arthritis, and rheumatoid arthritis, that fall into the
category of tumor necrosis factor alpha inhibitors, can cause a drug-induced lupus that differs from typical drug-induced
lupus. Medications like infliximab and etanercept can cause a drug-induced lupus that leads to an elevation in ANA as
well as dsDNA while having no effect on the anti-histone autoantibodies that normally occur with drug-induced lupus
caused by other medications (Choices A, B, and D).
Other systemic immunomodulators used to treat psoriasis such as ustekinumab (Choice E) have not been consistently
reported in association with ANA/dsDNA positive drug-induced lupus and this may be due to the inhibition of different
pro-inflammatory targets. Skin findings in TNF-alpha inhibitor drug-induced lupus can mimic the findings of acute SLE
(malar rash and/or discoid lesions), sub-acute cutaneous LE, and chilblains. Photosensitivity and purpura may also be
present in patients with this variant of drug-induced lupus. Additionally, systemic symptoms such as fever,
pancytopenica, phlebitis, thrombocytopenia, and serositis can occur in patients with drug-induced lupus caused by TNF-
alpha inhibitors. Drug-induced lupus that are anti-histone antibody positive in more than 75% of patients, as opposed to
approximately 20% in SLE. Drug induced lupus is caused by medications like hydralazine, procainamide and minocycline,
do not typically demonstrate the salient cutaneous features of acute SLE such as the malar rash or discoid lesions. In
these cases of drug-induced lupus systemic symptoms are more prominent then cutaneous findings.
81. The biopsy of a patient whom you suspect has dermatomyositis returns inconclusive. You refer him to general
surgery for a skeletal muscle biopsy, which you hope will confirm the diagnosis. The surgeon calls your office
requesting a specific site you wish to be biopsied. Which of the following locations would most likely demonstrate
findings consistent with dermatomyositis?
A. Deltoid muscle
B. Biceps muscle
C. Triceps muscle
D. Quadriceps muscle
E. Gastrocnemius (Calf) muscle
Correct answer: (C) Triceps muscle.

Explanation: In the absence of cutaneous findings, or if histopathology of cutaneous lesions cannot support a diagnosis
of dermatomyositis, a muscle biopsy can be a beneficial test for confirming dermatomyositis while ruling out other
inflammatory myopathies. While the deltoid muscle (Choice A), may be a more practical location to achieve skeletal
muscle biopsy, this muscle is typically spared from the inflammation associated with dermatomyositis. The triceps is
more commonly involved and is typically the first group of skeletal muscles involved in myopathy-associated
dermatomyositis. The bicep muscles (Choice B), can be involved in dermatomyositis, but inflammation may not extend to
this muscle group until later in the disease onset. While the quadriceps muscles of the lower extremities (Choice D) can
be involved in dermatomyositis, this location is not a practical site to perform a skeletal muscle biopsy. The calf muscle
(gastrocnemius, Choice E) a distal skeletal muscle of the lower extremity, is not typically involved in dermatomyositis.
82. A 29 year-old female patient of yours, with a known diagnosis of discoid lupus erythematosus, returns to your clinic
after failing to improve on topical and systemic corticosteroids, as well as a 6-month course of hydroxychloroquine.
Which of the following is the next best step in treating this patient?
A. Discontinuing hydroxychloroquine and initiating treatment with azathioprine
B. Continuing treatment with hydroxychloroquine while simultaneously initiating quinacrine
C. Discontinuing hydroxychloroquine and initiating treatment with dapsone
D. Discontinuing hydroxychloroquine and initiating treatment with systemic retinoids
E. Continuing treatment with hydroxychloroquine while simultaneously initiating thalidomide
36
Correct answer: (B) Continuing treatment with hydroxychloroquine while simultaneously initiating quinacrine.
Explanation: After failing a trial of hydroxychloroquine as monotherapy for the treatment of discoid lupus
erythematosus, next line therapy is typically the addition of a second anti-malarial such as quinacrine. Anti-malarial
therapy does not lead to rapid improvement in either cutaneous or systemic symptoms of SLE. A period of 2-3 months
may be required before any efficacy is demonstrated, and more time is needed before maximum efficacy can be
achieved, sometimes taking up to 6-8 years. The addition of a second anti-malarial can enhance the efficacy of
hydroxychloroquine and is the next therapeutic step in recalcitrant lupus erythematosus.
(A) Discontinuing hydroxychloroquine and initiating a systemic immunosuppressant such as azathioprine would not be
appropriate management in a patient with discoid lupus unless the patient has demonstrated a failure to respond to
combination anti-malarial therapy.
(D) (E) Discontinuing hydroxychloroquine and starting treatment with either retinoids, or simultaneous treatment with
thalidomide, are not next steps in the therapeutic ladder in treating lupus erythematosus, least not in patients who are
of child-bearing potential given their associated teratogenicity.
(C) Dapsone, has not demonstrated efficacy in the treatment of lupus erythematosus except in the rare subset of bullous
SLE.
83. Which underlying disorder is associated with the findings pictured below?
A. Protein deficiency
B. B3 deficiency
C. Zinc deficiency
D. Filaggrin mutation
ANSWER: B.
EXPLANATIONS:
B. TRUE: Niacin (B3) deficiency or pellagra presents with a classic triad of clinical features (dementia, diarrhea, and
dermatitis). Cutaneous findings include a photosensitive eruption that develops hyperpigmentation and superficial
desquamation.
A. FALSE: Protein-energy deficiency (Kwashiorkor) may present with dyschromia, pallor due to abdominal distention,
superficial desquamation (enamel paint spots), sparse hair, and thin nails. Pellagra spares the hair and nails.
C. FALSE: Zinc deficiency often mimics pellagra, but cutaneous lesions preferentially favor perioral and perineal locations.
D. FALSE: Filaggrin mutations are associated with ichthyosis vulgaris, which accompanies AD in 50% of cases.
37

Rheumatic and Systemic Disease Clinical Findings

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Rheumatic and Systemic Disease Clinical Findings

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Rheumatic and Systemic Disease

1. The following clinical picture depict a hereditary periodic fever syndrome:

Correct answer: (D) Muckle–Wells syndrome.

3. What patients have the highest incidence of SCC?

Correct answer: (A) Heart transplant patients.

Correct answer: (C) Lupus.

Correct answer: (E) All of the above.

Correct answer: (B) Palisading of histiocytes.

Correct answer: (B) Corkscrew hair.

Correct answer: (D) Anakinra.

Correct answer: (D) 10 attacks per day.

Correct answer: (C) Serum and urine protein electrophoresis.

A. pustules on the hands and soles

Correct answer: (D) Centromeric pattern.

Correct answer: (E) Histones.

Correct answer: (A) Anti-p155 autoantibodies.

Correct answer: (B) Elevated ferritin.

Correct Answer:A. Sex.

Correct answer: (C) Either choice A or B.

21. Which of the following is false regarding the condition below?

A. sildenafil can be used to improve hand dexterity

Correct answer: (B) Computerized tomography scan.

Correct answer: (B) 13%.

Correct answer: (C) Anaphylaxis.

Correct answer: (E) All of the above.

Correct answer: (C) Anti-Jo1 autoantibodies.

Correct answer: (E) Quinacrine and eye toxicity.

Correct answer: (D) Calcinosis cutis.

Correct answer: (A) ANA.

Correct answer: (B) Associated with Type I collagen antibodies.

34. Which of the following is not a characteristic of tumid lupus?

Correct answer: (A) Sudden onset and weight loss.

Correct answer: (E) Upper aerodigestive tract malignancy.

38. Which of the following regarding this condition is true?

A. associated with an IgG lambda paraproteinemia

Correct answer: (E) All of the above are true.

39. Which of the following associations is incorrect?

Correct answer: (E) Magnesium-Paronychial pustulosis.

40. What is the associated virus for the condition below?

Correct answer: (B) HHV-8.

Correct answer: (E) Edematous and boggy skin.

Correct answer: (A) Extra-cellular matrix protein 1.

Correct answer: (A) Urine porphyrins.

Correct answer: (C) Alpha-fodrin.

Correct answer: (A) Renal cell carcinoma.

Correct answer: (B) Glomeruloid hemangiomas, hypertrichosis, and hyperpigmentation.

53. Which of the following statements regarding treatment of dermatomyositis is FALSE?

54. Patients with juvenile dermatomyositis are at increased risk for?

Correct answer: (B) Calcinosis.

Correct answer: (C) Sun-protection with physical sunblock.

Correct Answer: B. Homogenous pattern and topoisomerase.

Correct answer: (D) Xanthomas.

Correct answer: (C) IgM gammopathy.

Correct answer: (C) Oral Aphthous Ulcers.

Correct answer: (A) Epidermis and superficial dermis only.

A. Saddle nose deformity

Correct answer: (C) Respiratory tract compromise.

Correct answer: (B)

Correct answer: (D) Choices A and B.

Correct answer: (C) Nail-Patella syndrome.

Correct answer: (C) Scleroderma.

Correct answer: (E) Anti-MDA5/CADM-140 autoantibodies.

Correct answer: (A) Pulmonary hypertension.