Background

A 46-year-old white man presents with diffuse musculoskeletal pain and morning stiffness
lasting about one hour. Six months ago, he developed a painful, diffusely swollen right fourth
toe. The pain was improved with over-the-counter naproxen, but the swelling never
completely resolved.
Over the next six months, pain spread to involve his cervical and lumbar spine; he also
developed swelling and pain affecting his right wrist and forearm, the left fourth distal
interphalangeal (DIP) joint, and the right ankle. In addition, tenderness was reported in the
area of the greater trochanter.
His past medical history was positive only for nasal pollen allergies, acne as a teenager, and
dandruff for the past five years. His family history is positive for myocardial infarction in his
father (at age 49 years), psoriasis, (also in his father), and stage 1 breast cancer in his mother,
who was treated with radiation and a lumpectomy, with good outcome to date.

Physical Examination and Workup

A physical examination confirmed swelling in the joints, as well as tenderness in the areas
that the patient had described as painful. Erythema and warmth were found over the involved
peripheral joints. The remainder of the physical examination was within normal limits except
for a nonpruritic, erythematous rash in the intragluteal cleft and multiple patches of a scaly
rash on his scalp that had been diagnosed as seborrhea. He had no rashes on the extensor
surfaces and no nail abnormalities.
Workup revealed a hemoglobin level of 11.8 g/dL and an otherwise normal complete blood
count (CBC). Hepatic and renal chemistry, urine analysis, rheumatoid factor (RF), and
antinuclear antibody (ANA) findings were normal. His serum uric acid level was 6.7 mg/dL
(normal range ≤7 mg/dL).
Radiographs of the hands revealed soft tissue swelling of the right wrist and forearm without
erosions or juxta-articular osteoporosis, and soft tissue swelling and an erosion at the left
fourth DIP joint.

Which of the following is the most likely diagnosis?

RF-negative rheumatoid arthritis
Gout
Osteoarthritis
Ankylosing spondylitis
Psoriatic arthritis

Discussion
The patient described the gradual onset of an inflammatory polyarthritis. The condition
involved peripheral joints, including a DIP joint; tendon sheaths, as exemplified by the
swelling in the forearm; and the lumbar and cervical spine. Physical examination confirmed a
pauciarticular, asymmetrical arthritis, and the presence of inflammation was indicated by the
erythema and warmth of the involved joints. Although the laboratory studies were
unrevealing, the patient’s radiograph showed erosive arthritis of a DIP joint, and the absence
of juxta-articular osteoporosis was noted. All of these findings, which also included a rash on
the scalp and intragluteal cleft, were consistent with psoriatic arthritis. The patient was started
on naproxen 500 mg twice daily and oral methotrexate 15 mg once weekly, with monitoring
of blood counts and liver function.
Psoriatic arthritis occurs in up to 1% of the adult white population but is less frequent in other
racial groups. Onset can occur at any age, including childhood and old age. The sex ratio is
equal. The incidence of psoriatic arthritis in patients with psoriasis may be as high as 30%,
although some studies have reported a lower incidence. Psoriasis typically precedes the onset
of arthritis, usually by no more than 10 years. However, in some patients, the onset is
simultaneous, and in a minority of cases, arthritis is the first symptom.[1,2,3]
Psoriatic arthritis is associated with a strong genetic predisposition; a family history of
psoriasis, arthritis, or both is often present. Multiple genes that predispose to either psoriasis
or psoriatic arthritis have been identified, including human leukocyte antigen (HLA)-
associated genes and non-HLA genes. Still, most of the genetic predisposition remains to be
determined. Although genes that predispose to psoriasis and those that predispose to psoriatic
arthritis overlap, important differences among the predisposing genes are observed.
The rash in psoriatic arthritis is erythematous and scaling. It most often occurs in plaques but
may develop in a guttate pattern or, rarely, as a diffuse erythema. An example is shown in the
image below.

Figure 1.

The scalp is frequently involved, although scalp psoriasis is often misdiagnosed as seborrhea.
When the rash involves skin folds, scaling may be absent. An example is shown in the image
below.

Figure 2.
Nail involvement is frequent and can include dystrophic changes, cracking, pitting, and
splinter hemorrhages.

Early in the disease, joint involvement is most often in the form of an asymmetrical arthritis.
The DIP joints are frequently involved, and cervical and lumbar spine involvement develops
in 50% of patients. Tendon sheaths are often affected as well, which may result in diffuse
swelling of the digits (so-called sausage digits). Diffuse, edematous swelling of a distal
extremity may also occur, due to extensive tendon sheath inflammation. As in ankylosing
spondylitis, involvement of tendon and ligament insertions (entheseal involvement) is
common.
A minority of patients with psoriatic arthritis present with a diffuse, symmetrical pattern of
arthritis or with isolated spinal involvement. In rare cases, patients have a pattern of severe,
highly destructive bone resorption that, when it occurs, often affects the small joints of the
hands and feet; this pattern is often refractory to treatment.[1,3]

Gastrointestinal symptoms are more common in patients with psoriatic arthritis than in the
general population. Eye disease and aortic valve disease are less common than in ankylosing
spondylitis. In contrast to rheumatoid arthritis, other systemic features are atypical.
Subcutaneous nodules do not occur, and other organ involvement is rare.

Laboratory studies are not helpful in establishing the presence of psoriatic arthritis, with no
tests being diagnostically specific for the disease. A mild anemia may be present, but white
blood counts are generally normal. RF and ANA test findings are positive only at the same
frequency as in the healthy population. Uric acid levels may be elevated in patients with
extensive skin disease but is usually normal. Similarly, the erythrocyte sedimentation rate and
C-reactive protein levels also are often normal, although they may be elevated in some cases.
Synovial fluid shows nonspecific inflammation with an elevated neutrophil count. Skin
biopsy with pathology can establish the diagnosis of psoriasis, but biopsy is not required in
most cases.
Radiologic findings can help to establish the diagnosis of psoriatic arthritis. [4]Features of the
condition that distinguish it from rheumatoid arthritis include asymmetrical joint
involvement, DIP joint disease, periosteal new bone formation, pencil-in-cup erosions
(Figure 3), joint fusion, sacroiliac and lumbar spine involvement, and absence of
periarticular osteoporosis.[1,3,4]
Figure 3.

In rheumatoid arthritis, symmetrical arthritis, sparing of the DIP joints and lumbosacral spine,
and juxta-articular osteoporosis on radiography are common. Less tendon sheath and
entheseal involvement is associated with rheumatoid arthritis, patients are usually RF-
positive, and skin rash is not a feature. Ankylosing spondylitis, an RF-negative disease, can
involve the entire spine; peripheral arthritis is generally limited to large central joints, such as
the hip and knee. Wrist, ankle, or DIP joint involvement is unlikely in ankylosing spondylitis,
as is rash.

The differential diagnosis of psoriatic arthritis also includes gout and osteoarthritis.

Gout is characterized by an episodic, self-limited, acute, monoarticular or pauciarticular
arthritis; the spine and sacroiliac joints are rarely involved, and no associated rash is present.
Uric acid crystals are present in the fluid from affected joints. In osteoarthritis, inflammation
is usually absent, wrist and ankle involvement is unusual, inflammation is generally absent,
and no rash occurs.

Tumor necrosis factor (TNF) inhibitors are highly effective for skin and joint disease and are
recommended as initial treatment for patients with active psoriatic arthritis. No data support
the superiority of any one TNF inhibitor over another.[1,4,5,6,7] If initial TNF inhibitor treatment
provides an inadequate response, switching to a different TNF inhibitor is recommended.

Nonsteroidal anti-inflammatory drugs (NSAIDs) may be helpful for joint pain in psoriatic
arthritis, but they do not alter joint progression or benefit skin disease. Methotrexate in higher
doses is effective for psoriasis, but neither it nor other disease-modifying antirheumatic drugs
(DMARDs), including sulfasalazine and cyclosporine, have been shown to provide long-term
benefits in delaying progression in patients with erosive joint disease. DMARDs may be used
as initial treatment in patients without severe disease who prefer starting with oral therapy or
have a contraindication to TNF inhibitors.
Antimalarials are generally avoided, since they have been associated with a severe, albeit
rare, skin reaction. Corticosteroids are used, but tapering of corticosteroids has been
associated with flares of skin disease. Local injection of corticosteroids can be useful for the
management of individual joints and tendon sheath involvement.
Other, more recently approved biologics are beneficial in patients with an unsatisfactory
response to TNF inhibitors. These include several inhibitors of interleukin (IL)-17, which are
highly effective for psoriasis; ustekinumab, an IL-12/23 inhibitor; abatacept, a CTLA4-Ig
inhibitor, tofacitinib, a JAK inhibitor; and apremilast, a phosphodiesterase-4 inhibitor. Other
biologic agents for psoriatic arthritis are in clinical trials.[8]
After the patient in this case began the aforementioned treatment with naproxen and oral
methotrexate, there was some improvement in the skin rash but little change in the arthritis,
which spread to additional joints. A TNF inhibitor was added to the treatment, and over the
next 3 months gradual improvement was observed in the patient’s arthritis, which became
almost inactive. Naproxen was discontinued, and the methotrexate dose was decreased back
to 15 mg weekly. The patient remains on this treatment regimen, with continued excellent
response.

Question 1 of 2

Which of the following is not a characteristic finding in psoriatic arthritis?

DIP joint arthritis
Tendon sheath inflammation
Lumbar spine involvement
Juxta-articular osteoporosis
Asymmetrical arthritis

Question 2 of 2

Which of the following suggests psoriatic arthritis rather than ankylosing spondylitis?
Negative RF
DIP joint and wrist arthritis
Sacroiliac joint arthritis
Hip and knee arthritis
Entheseal arthritis

1. Al Hammadi A, Aljefri K. Psoriatic Arthritis. Medscape Drugs & Diseases. Last

updated: Dec 12, 2019. Available at: http://emedicine.medscape.com/article/2196539-
overview.
2. Wilson FC, Icen M, Crowson CS, et al. Incidence and clinical predictors of psoriatic
arthritis in patients with psoriasis: a population-based study. Arthritis Rheum. Feb 15
2009;61(2):233-9. Source
3. Dhir V, Aggarwal A. Psoriatic Arthritis: A Critical Review. Clin Rev Allergy
Immunol. Apr 2013;44(2):141-8. Source
4. Mease P, Goffe BS. Diagnosis and treatment of psoriatic arthritis. J Am Acad
Dermatol. Jan 2005;52(1):1-19. Source
5. Saad AA, Symmons DP, Noyce PR, et al. Risks and benefits of tumor necrosis factor-
alpha inhibitors in the management of psoriatic arthritis: systematic review and
metaanalysis of randomized controlled trials. J Rheumatol. May 2008;35(5):883-
90. Source
6. Soriano ER, McHugh NJ. Therapies for peripheral joint disease in psoriatic arthritis.
A systematic review. J Rheumatol. Jul 2006;33(7):1422-30. Source
7. Singh JA, Guyatt G, Ogdie A, et al. 2018 American College of
Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic
Arthritis. Arthritis Rheumatol. 2019;71:5-32. Source
8. Gladman DD. Psoriatic Arthritis. Dermatol Ther. Jan-Feb 2009;22(1):40-55. Source