IMMUNE SYSTEM erythema

DISORDERS OF IMMUNITY, -
-
initiates and regulates inflammation
Produces reactions against non-infectious foreign agents

HYPERSENSITIVITY AND -

-
When present, slows down or speeds up the growth and spread of malignant
tumors
Can activate fibrinolysis and blood coagulation
INFLAMMATION -
-
Can control normal wound healing
dynamic system of cells and humoral factors that protects and maintains life
and helps to mend damaged tissues
- Can induce cells to liberate hormone-like substances

Skin and mucous membrane acts as interfaces between the environment and
homeostatic physiologic milieu of body organs URTICARIA

Innate vs Adaptive Immune Response IMMUNE SYSTEM erythema

HUMORAL
INNATE ADAPTIVE - Immunologic responses involving immunoglobulins
Immediate response Slow response - Immunoglobulins composed of at least 2 small amino acid chains and 2 large amino acid chains
Non-specific; includes physical barriers (skin and Specific
mucosal barriers)
B lymphocytes
Short-lived Long-lasting - Constitute approx. 10% of circulating cells
- Have receptors for specific antigens on their surface
No memory Have memory
Plasma cells
Soluble factors such as complement, antimicrobial Initiated by Langerhans cells in the epidermis and by
peptides, chemokines and cytokines dermal dendritic cells.
Antibodies
Monocytes/macrophages, dendritic cells, NK cells, T lymphocytes and antibodies produced by B - Immunoglobulins that react with antigens are called
polymorphonuclear WBCs lymphocytes/ plasma cells antibodies

URTICARIA

IMMUNE SYSTEM erythema MAJOR CLASSES OF IMMUNOGLOBULINS

Immunoglobulins that react with antigens are called antibodies

CELL-MEDIATED IgG IgM IgA IgE IgD

T lymphocytes
- Involves T cells and lymphokines - Major - Largest - Synthesized - Most are - Role in
- Constitue 80-90% of circulating lymphocytes
- Antigen must be processed by cells of the and majority of lymphocytes present in the human Ig immunoglob by plasma attached to serum
mononuclear-phagocytic system before a T cell can initiate a normal skin ulin cells of the tissue mast cells unknown
cell-mediated immune response - Responsible molecule GIT and - An antigen - Function
T Helper cells for respiratory bridging 2 IgE primarily as
- Interacts with B cells to promote proliferation
After contact with the antigen, the lymphocytes undergo clonal and antibody synthesis
long-lasting - First tract molecules cell
proliferation immunity antibody - Acts as persuades mast membrane
T Suppressor cells detected protective cell to secrete receptor
- Interacts with B cells to inhibit further Ig after coating to granules that
Triggered by Interleukin-I (produced by macrophage keratinocyte) and secretion and differentiation initiation of neutralize are mediators of
sustained by Interleukin-2 (produced by lymphocytes) an immune virus, toxins anaphylaxis
response

Daughter T cells enter the circulation to induce immunity

Fix complement
✔ ✔ ✖ ✖ ✖
URTICARIA
Cross the
placenta
✔ ✖ ✖ ✖ ✖
MAJOR CLASSES OF IMMUNOGLOBULINS COMPLEMENT SYSTEM erythema
Immunoglobulins that react with antigens are called antibodies

TYPE I TYPE II TYPE III TYPE IV TYPE V 1. CLASSICAL PATHWAY

- anaphylactic
reactions
- involve IgE or IgG
- binding of antigen to
IgE molecules on
mast cells or
basophils -> liberates
histamines,
leukotrienes, heparin
-> induce vasodilation
-> leakage of CR
Urticaria
● IgG and IgM activate complement by binding to a small portion of C1 called C1q
- Cytotoxic reaction - All immune - Cell-mediated - Role in
- Normally involve complex immune reactions serum ● C5
either IgG or IgM reactions unknown ● potent chemotactic factor
- Binding of antigen
- Either involves - Function ● Brings polymorphonuclear leukocytes and mononuclear phagocytes into the
by these IgG or the IgG, IgM or primarily as
IgM activates area
IgA cell
complement and membrane
● Activation generates chemicals that lead to engulfment of antigen or infectious
results in either agent to which the antibody is bound
receptor
cytolysis or
engulfment of Ag
● Engulfing phagocyte kills the antigen
by phagocytic cells
2. ALTERNATIVE PATHWAY
Bullous pemphigoid Leukocytoclastic Delayed hypersensitivity ● Doesn’t require antibodies to initiate activation of the complement system
URTICARIA
vasculitis elicited w/in 48 hrs by
application or infection
of antigen to the skin

INFLAMMATION erythema SKIN AS AN IMMUNOLOGIC ORGAN erythema

- Skin contains cells necessary to induce an immune response and can be the
- characterized by redness, heat, pain and swelling and sometimes arena where antigens elicit inflammation ANGIOEDEMA

loss of function
- Langerhans cells are interspersed among keratinocytes. Dendrites of
- pattern and duration of inflammatory response is dependent upon keratinocytes intercalate in the intercellular spaces. Here antigens are
- Rate of spread trapped, processed and presented to T helper cells
- Mode of spread
- Number of infectious organisms at inoculation site
- In contact with antigen, these T cells secrete lymphokines leading to
inflammation

URTICARIA URTICARIA
- Many inflammatory skin conditions result from immune responses elicited in
the skin

CELLS IN INFLAMMATORY DISEASE

LYMPHOCYTES MONOCYTES NEUTROPHIL EOSINOPHIL BASOPHIL
URTICARIA AND ANGIOEDEMA erythema
SIZE < 10μ 12-20μ 10-15μ 10-15μ 10-15μ

NUCLEUS round, oval, indented or segmented Bilobed, centrally or 2-3 lobes, centrally Definition
reniform nucleus 2-5 lobes eccentrically situated has situated
course chromatin

Cytoplasmic granules are

CYTOPLASM Contains little cytoplasm grayish-blue cytoplasm
contains fine, azurophilic
Cytoplasmic granules granules
usually absent cytoplasmic granules often
present
FUNCTION Crucial in the Macrophage in tissues
development of humoral Involved with phagocytosis,
and cell-mediated antigen-processing and
immunity presentation, tumor cell
cytotoxicity and secretion of
inflammatory, hematopoietic
and immune-modulating
mediator
Contains fine, pink or
violet-pink granules
Contains primary and
secondary granules
Destruction of invading
microorganisms,
particularly bacteria
through a process of
phagocytosis,
degranulation and
activation of the
respiratory burst
larger than neutrophil specific
granules
Orange to red,
uniformly-sized, circular to
elliptic-shaped
membrane-bound granules
Chief function include killing
parasites and dampening of
hypersensitivity reactions
- Skin lesion consisting of a wheal and flare reaction in which localized
Contains numerous
large, round, oval intracutaneous edema (wheal) is surrounded by an area of redness
purplish-black granules
(erythema) that is typically pruritic.
- involves superficial dermis and venular plexus
IgE-mediated
degranulation of
mediators that occur in - Blanch with pressure
immediate
hypersensitivity reactions
URTICARIA
URTICARIA erythema ANGIOEDEMA erythema

Clinical Manifestations ANGIOEDEMA

Definition
WHEALS
- pinpoint to palm-sized or larger and - same pathogenic mechanisms as urticaria, and usually coexists with
enlarge by peripheral extension to urticaria
become confluent which result to
bizarre geographic or serpiginous
configurations
- involves deep dermis and subcutaneous tissue and swelling
- Rarely persist longer than 12-24 hrs,
duration transient
- Prickly sensations commonly - overlying skin may be erythematous or normal
precede wheal development
- Associated symptoms may include:
coryza, respiratory distress, URTICARIA - less pruritis, +/- burning or pain
abdominal pain and hoarseness

URTICARIA erythema erythema

PATHOGENESIS

Classification of Urticaria
ACUTE
< 6 weeks
- adverse reactions to medication
or food
- Infectious process
- contactants
- Parenteral agents (insect bites,
diagnostic material)
- Mast cell: considered the major common pathway involved in urticaria
CHRONIC - Autoimmunity
- Cellular infiltrate: mast cells, neutrophils, basophils, eosinophils,
> 6 weeks complement activation and C5a release
- Chronic immune urticaria - Basophils are hyporesponsive to anti-IgE or basopenia
- Chronic idiopathic urticaria
- Activation of extrinsic coagulation cascade
- Release of bradykinin
URTICARIA URTICARIA

CLINICAL FINDINGS
URTICARIA erythema
ANGIOEDEMA IMMUNE-MEDIATED URTICARIA erythema
circumscribed, raised, erythematous, pruritic, edematous process
evanescent areas of edema
superficial portion of dermis deep dermis and/or subcutaneous and IgE DEPENDENT NON-IgE DEPENDENT
submucosal layers
Atopic Cytotoxic
May occur in any location together or Commonly affects face, lips, or cheeks and Nonatopic Immune Complex
individually periorbital areas
May also affect tongue, pharynx, larynx Allergic urticaria is usually acute and react to Serum sickness
portion of an extremity food, inhalant or other type of allergen Urticarial vasculitis: hypocomplementemia
Mold allergies are implicated in chronic Transfusion reactions
Highly pruritic; May be painful but not pruritic urticaria
Arise suddenly, rarely persist longer than
24-36 hours Involve Type 1 Hypersensitivity Involve TypeURTICARIA
2 and 3 Hypersensitivity
Recur for indefinite periods
COMPLEMENT-MEDIATED URTICARIA
erythema erythema
PHYSICAL URTICARIA
HEREDITARY ANGIOEDEMA - Wheal formation may be reproducibly induced by physical stimulus

Stroking or pressure force ELECTROMAGNETIC Solar urticaria

- Transmitted by a mendelian dominant gene ● Immediate onset IRRADIATION
Simple dermatographism
Symptomatic dermatographism Aquagenic urticaria
- Acute, recurrent self-limited episodes of transient edema involving the skin and MECHANICAL ● Delayed onset
WATER
mucosa of the GIT and respiratory tract Delayed pressure urticaria EXERCISE Exercise-induced anaphylaxis
Delayed dermatographism
- Due to a functional deficiency of the protein inhibitor of the activated first Vibratory force
Vibratory angioedema
component (C1) of the complement system that mediates the development of
angioedema Heat
● Localized heat urticaria
- Deficient or nonfunctional serum Alpha-2 globulin inhibitor ●
Cold
Cholinergic urticaria
THERMAL ● Familial cold urticaria
- Diagnosis: diminished levels of C1INH or decreased functional activity of C1INH ● Acquired cold urticaria
Primary cold urticaria
- Therapy: administration or enhanced production of C1INH, educate to seek Secondary cold urticaria
immediate care once swelling of upper respiratory tract occurs

IMMEDIATE ONSET IMMEDIATE ONSET

SIMPLE DERMATOGRAPHISM SYMPTOMATIC DERMATOGRAPHISM

- Usually idiopathic - Usually idiopathic

- Most common form of mechanically-induced - Diagnosis involves wheal formation after minor trauma using a
physical urticaria dermographometer
- Trauma results in an erythematous, pruritic wheal formation within several
- Wheal formation occurs at a lower threshold of minutes up to several hours
pressure or force than it would the normal
population - Supportive treatment include limiting or reducing trauma to the skin and an
H1 blocker alone or in combination with an H2 blocker.
- Wheal formation occurs within a few minutes and
disappears within an hour
- No treatment necessary

DELAYED-ONSET DELAYED-ONSET
DELAYED PRESSURE URTICARIA (pressure-induced)
DELAYED DERMATOGRAPHISM
- May be induced with a dermographometer
- Develop wheals or deep symptomatic painful angioedema after a few hours that
- (+) response: development of linear wheals between 1-6 hrs after after
last many hours or days ff the stimulus
stroking of the skin
- Wheals occur following manual activities , walking, sitting
- Areas most commonly affected: distal extremities, trunk, buttocks and lips
- Flu-like syndrome and leukocytosis may occur concomitantly
- May coexist with chronic idiopathic urticaria or angioedema
- (+) response: delayed whealing or angioedema after applying graduated static
weights to the back or suspending a 15 lb weight over the shoulder for 10 mins
- Supportive treatment: antihistamine, aspirin and NSAIDs may be of use.
Systemic corticosteroids for disabling conditions
COLD URTICARIA HEAT URTICARIA
URTICARIA URTICARIA
- Acquired and inherited forms of cold urticaria/ angioedema; - Wheals and flares developing within minutes after local heat exposure and disappear
familial form is rare after a few hours
- Wheals and flares occurs within minutes and persist up to 1 - Spread to the area exposed to the heat, irregardless of sweating or core body
hr after exposure to change in ambient temperature and temperature
direct contact with cold objects
- Rarely, systemic symptoms such as headaches, dizziness, gastrointestinal colic,
- Diagnostic Cold Contact Test: elicitation of a wheal after the application of ice wheezing, and syncope may develop
- Hypotensive and syncope may occur if entire body is cooled

- In rare instances are associated with children with infectious mononucleosis

- Passive transfer of cold urticaria by intracutaneous injection of serum or IgE to the skin of
normal recipient has been documented

CHOLINERGIC URTICARIA SOLAR URTICARIA

- Develops after an increase in core body - Pruritus and erythema along with urticarial
temperature such as during a warm bath, wheals develop within minutes after exposure of
prolonged exercise, emotional stress or episodes of the skin to ultraviolet light and visible light
fever
wavelengths (290-700 nm)
- Characteristically small 1-4 mm pruritic wheals with
or without surrounding flares - Reaction clears spontaneously within hours
- Usually pruritic and involves trunk and proximal - Areas of the skin usually protected by clothing such as trunk or thighs are
extremities more susceptible than areas of skin chronically exposed to UV light.
- More common in children, adolescents and young
adults - May accompany headache, dizziness and nausea

- Diagnosis: active exercise or passive heat - Treatment: avoid exposure of skin to urticariogenic wavelength of light, use of
challenge (43 C bath) for 20-30 minutes proper clothing and protective external measures such as sunscreens,
- Supportive treatment: H1 blocker cautious induction of sunlight tolerance in a patient

AQUAGENIC URTICARIA URTICARIAL VASCULITIS

AQUAGENIC URTICARIA

- Water-soluble antigen located in stratum corneum is thought to diffuse into

the dermis to cause immune-mediated release from sensitized mast cells - Recurrent urticarial lesions lasting for more than 24 hrs resulting in
- Water causes distinctive tiny, punctate perifollicular wheals usually pigmentation
involving the neck, arms and upper trunk occurring within 30 mins
- Supportive treatment: H1 blocker may attenuate wheal formation
APPROACH TO PATIENT WITH URTICARIA APPROACH TO PATIENT WITH URTICARIA
HISTORY HISTORY
Acute Urticaria (< 6 weeks) Chronic Urticaria (> 6 weeks)
- Acute urticaria associated with viral illnesses in children - Associated with angioedema and more problematic in the autoimmune
- Associated with infectious mononucleosis and prodrome to hepatitis B group
- Either chronic idiopathic urticaria or chronic autoimmune urticaria
- Suspect an allergic reaction of present for days or weeks at a time (<6 - Swelling associated with chronic urticaria can affect hands, feet, eyes,
weeks) or occurs recurrently for similar intervals cheeks, lips, tongue and pharynx
- Recent exercise
- Exposure to warm or cold stimulus
- If hives last < 2 hrs, cause usually d/t physical urticaria
- Delayed pressure urticaria: first appear 3-6 hours after initiating stimuli and
typically last 12-36 hrs

APPROACH TO PATIENT WITH URTICARIA APPROACH TO PATIENT WITH URTICARIA

PHYSICAL EXAMINATION
Can be identified by their characteristic appearance:
- Cholinergic urticaria: small wheals with a large erythematous flare
- Dermatographism: linear wheals
- Light or cold-induced: localization of lesions to exposed areas
LABORATORY FINDINGS
No routine lab testing
Evaluate chronic urticaria/ angioedema: thyroid function tests, assay for antimicrosomal
and antithyroglobulin antibodies, autologous skin tests
Histamine release assay for anti-IgE receptor or anti-IgE antibodies
Detection of cryoproteins in acquired cold urticaria
Antinuclear antibody in patients with solar urticaria
Assess serum complement proteins to identify patients with urticarial venulitis or serum
sickness
Skin biopsy of chronic urticarial lesions to identify urticarial venulitis

APPROACH TO PATIENT WITH URTICARIA HENOCH SCHOENLEIN PURPURA

TREATMENT OF ACUTE URTICARIA
• Mainstay Supportive Treatment: 2ND Generation Non-sedating
Antihistamine
• Omalizumab inhibits circulating Ig-E, effective for almost all types
• Short course of Corticosteroid
• Identify and eliminate exogenous and endogenous causes
PATHOGENESIS
• IgA-antibody immune complexes caused by antigenic exposure from an
infection or medication deposit in the small vessels (usually capillaries) of the
skin, joints, kidneys, and gastrointestinal tract. This results in an influx of
inflammatory mediators such as prostaglandins.
ETIOLOGY
• Occurs predominantly in children with peak incidence at 5-6 yo but may also
occur in adults
• Often preceded by a history of recent URTI especially with β-hemolytic
Streptococcus
• Coxsackievirus, hepatitis A, hepatitis B, Mycoplasma, parvovirus B19,
Campylobacter, Varicella, and adenoviruses
HENOCH SCHOENLEIN PURPURA HENOCH SCHOENLEIN PURPURA
CLINICAL MANIFESTATIONS DIAGNOSIS
• Palpable, nonpruritic purpura and petechiae that most • Based on clinical findings
commonly affect the lower extremities (extensor surfaces) and • Urinalysis
buttocks. Other sites of involvement include the skin, synovia,
GIT and kidneys DIFFERENTIAL DIAGNOSIS
• Lesions change from red to purple and then become • IgA Nephropathy
rust-colored before they fade • Idiopathic Thrombocytopenic Purpura
• Symptoms may include colicky abdominal pain, melena, • Hemolytic Uremic SYndrome
arthralgia, and hematuria
• Spread of purpura to upper parts of the trunk is a predictive TREATMENT
factor for renal involvement
• Joint pain and fever: Acetaminophen and NSAIDs
• however, nonsteroidal anti-inflammatory medications should most
certainly be avoided if there is gastrointestinal or renal involvement

TELANGIECTASIA TELANGIECTASIA
- Permanent dilatation of cutaneous venules that appear as fine wires, or spiders
characterized by an accentuated pulsating punctum with radiating limbs A. NEVUS FLAMMEUS
- Pregnancy may be assoc. w/ collagen vascular diseases B. STURGE-WEBER SYNDROME
C. SPIDER NEVUS
PATHOGENESIS
• Most cases are idiopathic
• Hypersensitivity reaction to an antigen
• Has been linked to cutaneous or systemic infections, malignancy, drugs,
certain disease states, pregnancy

NEVUS FLAMMEUS STURGE-WEBER-SYNDROME

- Dilated vessels are secondary to a - Large nevus flammeus occupying one side of the face
congenital weakness in the vessel wall and scalp associated with ipsilateral retinal and
cerebromeningeal-telangiectasia
- characterized by small reddish-blue patches
with an irregular border
- Common sites: posterior nuchal zone, lateral
aspect of the nose and upper eyelids
- Localized nevus flammeus has tendency to
fade and become smaller with age
SPIDER NEVUS SPIDER NEVUS
CAUSES
- Idiopathic vascular spider ❖ Genetic
- Type of telangiectasia that presents with symmetrically radiating thin branches ➢ Vascular nevi
■ Nevus flammeus
- Appears most commonly on the exposed areas- face, arms, and hands and rarely ➢ Congenital neuroangiopathies
below the umbilicus. The mucous membranes of the lips and nose may be involved. ■ Ataxia telangiectasia
- Lesions tend to be solitary but when numerous, are most commonly associated with ■ Sturge-Weber Syndrome
➢ Congenital Poikiloderma
liver disease
- Children and adolescents: usually idiopathic or nevoid
❖ Hormonal
- Adults: pregnancy, associated with cirrhosis and metastatic carcinoma of the liver
➢ Pregnancy
- Appear during first few months of pregnancy and disappear within 6 weeks after ➢ Corticoid-induced
delivery ■ Cushing’s syndrome, High
dose prolonged estrogen TX
❖ Component of a Primary
Cutaneous Dss
➢ Rosacea
➢ Varicose veins
➢ Basal Cell Carcinoma
➢ Xeroderma pigmentosa
➢ Pseudoxanthoma elasticum
❖ Physical Damage
➢ Actinic Dermatitis
➢ Physical trauma
➢ Post-surgery especially in suture lines
under tension, after rhinoplasty

ERYTHEMA ANNULARE CENTRIFUGUM ERYTHEMA ANNULARE CENTRIFUGUM

PATHOGENESIS RISK FACTORS
• Most cases are idiopathic • Dermatophyte infections
• Hypersensitivity reaction to an antigen • Tinea pedis
• Has been linked to cutaneous or systemic infections, malignancy, drugs, • Other cutaneous infections
certain disease states, pregnancy • Molluscum contagiosum
• Herpes zoster
• Systemic infections
• Epstein-Barr virus
• HIV

ERYTHEMA ANNULARE CENTRIFUGUM ERYTHEMA ANNULARE CENTRIFUGUM

PATHOGENESIS CLINICAL FEATURES
RISK FACTORS • Pink papule, expands centrifugally → forming an annular or polycyclic
• Lymphoproliferative malignancies plaque with central clearing
• Paraneoplastic erythema annulare centrifugum eruptions • Superficial variant
• Such as lymphomas, leukemias • Slightly elevated, desquamation at inner margin (“trailing scale”)
• Often precedes the diagnosis of the underlying malignancy • Deep variant
• Occurs as a result of cytokine or tumor-associated factors • Indurated, firm border, without prominent scaling
• Drugs
• Finasteride
• Azacitidine
• Pegylated interferon-α2a , ribavirin
• Rituximab
• Ustekinumab
• Amitriptyline
• Gold sodium thiomate
 ERYTHEMA ANNULARE CENTRIFUGUM
CLINICAL FEATURES
• Pruritus - most common symptom
• Residual scarring
• Postinflammatory hyperpigmentation
• Most frequent sites of involvement
• Buttocks, thighs, and trunk
• Lower extremities, trunk (most common sites of involvement in a
series of cases)
• Based on extent of involvement
• 58% - lesions located on only one site
• 28% - 2 sites
• 14% - ≥3 sites (generalized)

ERYTHEMA ANNULARE CENTRIFUGUM ERYTHEMA ANNULARE CENTRIFUGUM

DIAGNOSIS DIAGNOSIS
PATHOLOGY PATHOLOGY
• Dense perivascular infiltrate composed of lymphocytes, histiocytes, • 2 distinct histologic patterns
occasional eosinophils • Superficial type
• Epidermal changes that correspond to clinical findings are
• “Coat-sleeve” pattern observed
• The infiltrate as a result of the well-demarcated distribution that tightly • Parakeratosis, hyperkeratosis, spongiosis, and/or vacuolar
wraps around blood vessels degeneration
• Perivascular infiltrates more prominent in upper dermis
• Deep type
• Epidermal changes absent or minimal
• Mild edema in papillary dermis
• Perivascular infiltrates involving vascular plexuses in both upper &
lower dermis

ERYTHEMA ANNULARE CENTRIFUGUM ERYTHEMA CHRONICUM MIGRANS

MANAGEMENT PATHOGENESIS
• Topical corticosteroids • Occurs at the site of the bite of an Ixodes tick carrying pathogenic strain
• Topical vitamin D analogs of B. burgdorferi
• Antihistamines (if pruritus) • Ixodes ticks acquire B. burgdorferi when feeding on an infected host
• Systemic corticosteroids • Bacteria survive in a protected environment in the tick midgut epithelium
• Cessation → rebound recurrence • Surface lipoproteins outer-surface protein (Osp) A and OspB.
• Antifungals & antibiotics (fluconazole, erythromycin, metronidazole) • Infected ticks transmit B. burgdorferi to new hosts through salivary glands
• OspC
• Salivary gland invasion
• Early colonization and infection of new hosts
• Bind to Salp15 (tick salivary protein; inhibits components of host
immune system)
ERYTHEMA CHRONICUM MIGRANS ERYTHEMA CHRONICUM MIGRANS
PATHOGENESIS CLINICAL FEATURES
• Cutaneous manifestation of early localized Lyme disease that occurs at CUTANEOUS FINDINGS
the site of the bite of Ixodes species ticks infected with Borrelia • 3 stages: early localized, early disseminated,
burgdorferi chronic disease
• Characterized by annular erythema that expands to create a “bull’s-eye” • Erythema migrans at the initial site of the tick
appearance bite
• Seen in 70-80% of individuals with Lyme disease • Hallmark of cutaneous finding of the 1st
RISK FACTORS stage of Lyme disease
• Human behaviors that increase exposure to infected ticks • Erythematous expanding annular plaque
• Time outdoors in endemic areas with a central area of clearing (Bull’s eye
• Lack of protective clothing lesion)
• Geographic location
• Seasonal patterns in tick activity

ERYTHEMA CHRONICUM MIGRANS ERYTHEMA CHRONICUM MIGRANS

CLINICAL FEATURES CLINICAL FEATURES
CUTANEOUS FINDINGS CUTANEOUS FINDINGS
• Erythema migrans • Erythema migrans
• Most common associated symptoms: • At time of presentation
warmth, pruritus, pain • Mean diameter 10-16cm
• Can be asymptomatic • Larger lesions on trunk
• Sometimes vesicular • Smaller lesions on lower extremities
• Primary lesions: in area where tick bites • Multiple lesions
occur and go unnoticed (trunk, axillae, • Multiple tick bites
groin, popliteal fossae) • Spirochetemia
• Grow centrifugally • Lymphatic spread
• At a rate of up to 3cm per day

ERYTHEMA CHRONICUM MIGRANS ERYTHEMA CHRONICUM MIGRANS

CLINICAL FEATURES CLINICAL FEATURES
CUTANEOUS FINDINGS NONCUTANEOUS FINDINGS
• Erythema migrans • Regional lymphadenopathy
• Ticks must be attached for at least 24hours • Arthralgias
before bacteria is transmitted → erythema • Arthritis
migrans at site of bite (7-14 days after tick • Myositis
detachment) • Pancarditis
• 70-80% develop lesions of erythema • Facial palsy
migrans • Conjunctivitis
• 45% presenting with erythema migrans • Hepatitis
have spirochetemia
ERYTHEMA CHRONICUM MIGRANS ERYTHEMA CHRONICUM MIGRANS
CLINICAL FEATURES CLINICAL FEATURES
COMPLICATIONS COMPLICATIONS
• Due to untreated Lyme disease • Borrelial lymphocytoma
• Second stage of Lyme disease • Benign reactive lymphoid hyperplasia in response to untreated
• Widespread spirochete dissemination Borrelia infections
• Neurologic, rheumatologic, cardiac involvement • Seen in early disseminated stage of Lyme disease
• Third stage of Lyme disease • Acrodermatitis chronica atrophicans
• Persistent neuroborreliosis • Typical of chronic Lyme disease
• Severe erosive arthritis • Characterized by enlarging, edematous plaques on the distal
• Acrodermatitis chronica atrophicans extremities with a bluish-red hue that evolve into atrophic plaques

ERYTHEMA CHRONICUM MIGRANS ERYTHEMA CHRONICUM MIGRANS

DIAGNOSIS DIAGNOSIS
• Clinical presentation, history of possible tick exposure PATHOLOGY
LABORATORY TESTING • Similar to other gyrate erythemas
• CDC: 2-step process to support diagnosis • Mild inflammatory infiltrates
• Enzyme immunoassay or indirect immunofluorescence assay • Nonspecific
• Detect antibodies • Lymphocytes & occasional eosinophils and plasma cells,
• If positive or equivocal, proceed to Western Blot concentrated around blood vessels
• Western blot analysis • Silver stains (Warthin-Starry stain)
• If positive = confirms diagnosis • Spirochetes in skin (B. burgdorferi)
• Not performed without positive or equivocal antibody test due
to risk for false-positive results

ERYTHEMA CHRONICUM MIGRANS ERYTHEMA CHRONICUM MIGRANS

MANAGEMENT MANAGEMENT
MEDICATIONS MEDICATIONS
• Early stages of Lyme disease • Prophylaxis: single dose of doxycycline
• Appropriate systemic antibiotics • To decrease risk of developing Lyme disease
• Doxycycline, amoxicillin, cefuroxime • Individual from an endemic area
• Disseminated, advanced disease with neurologic or cardiac • Bitten by a tick identified as I. scapularis
involvement • Tick attachment for longer than 36 hours
• Intravenous antibiotics • Started within 72 hours of tick removal
ERYTHEMA GYRATUM REPENS ERYTHEMA GYRATUM REPENS
PATHOGENESIS CLINICAL MANIFESTATIONS
• Cross-reaction between tumor antigens and cutaneous antigens • Characteristic wood-grain appearance
• Similar deposits of IgG & C3 in the basement membrane zone of the skin • Multiple, erythematous, annular
and in the associated neoplasm simultaneously lesions (rapid rate up to 1cm/day)
• Responsible antigens not identified • As lesions spread, they form
• Langerhans cells in the epidermis in lesions concentric rings
• Epidermis has superficial scale at
edges
• Pruritus

ERYTHEMA GYRATUM REPENS ERYTHEMA GYRATUM REPENS

CLINICAL MANIFESTATIONS DIAGNOSIS
• Onset occurs ~1 year after diagnosis of malignancy • Based on clinical appearance
• Additional associated cutaneous findings • Presence of a known malignancy
• Ichthyosis • Appropriate screening for possible underlying neoplasm
• Palmoplantar keratoderma PATHOLOGY
• Nonspecific
• Common epidermal changes
• Mild spongiosis
• Hyperkeratosis
• Parakeratosis
• Perivascular infiltrate (lymphocytes, histiocytes, eosinophils)

ERYTHEMA GYRATUM REPENS ERYTHEMA GYRATUM REPENS

DIFFERENTIAL DIAGNOSIS MANAGEMENT
• Figurate erythemas • Topical corticosteroids (symptomatic relief)
• Erythema annulare centrifugum • Treatment of underlying malignancy
• Erythema marginatum • Recurs in cases of relapse or metastases
• Erythrokeratoderma variabilis
• Psoriasis
• Pityriasis rubra pilaris
• Tinea corporis
• Tinea imbricate
• Mycosis fungoides
• Bullous pemphigoid
• Linear IgA bullous dermatosis
 ERYTHEMA MULTIFORME ERYTHEMA MULTIFORME
PATHOGENESIS CLINICAL MANIFESTATIONS
• Typical cutaneous lesion: highly regular, wheal-like
• Tissue damage is a result of TYPE III immune complex reaction erythematous papule or plaque that persists for 1 wk with a
• Blood vessel damage is a result of TYPE II reaction violaceous or dark center that regress or relapse giving rise to
concentric rings of color
ETIOLOGY • Mucous membrane lesion: erosions with fibrinous deposits
• Underlying infection with occasional intact vesicles and bullae with predilection to the
lips
• MCC is recurrent HSV infxn
• Mycoplasma pneumoniae • Symmetric, acral distribution on the extensor surfaces of the
• Drugs administered (phenobarbital, lithium) extremities, face and neck
• Idiopathic causes
• Centripetal spread
• (+) Cervical LAD, fever, may drool blood-stained saliva,
painful genital erosions that lead to reflex urinary retention

ERYTHEMA MULTIFORME TOXIC EPIDERMAL NECROLYSIS

DIAGNOSIS PATHOGENESIS
• No specific lab findings • Immunologic pattern of early lesions suggests a cell-mediated cytotoxic
• Suspected Mycoplasma pneumoniae: PCR assay of throat swab, CXR, reaction against keratinocytes leading to massive apoptosis
serologic detection
• Biopsy is done to rule out other diagnoses • Cytotoxic T-cells develop and are usually specifically directed against the
native form of a drug rather than against a reactive metabolite
DIFFERENTIAL DIAGNOSIS • Genetic susceptibility also plays an impt role
• Urticaria
• Maculopapular Drug eruptions ETIOLOGY
• Lupus (Rowell Syndrome)
• Drugs (Allopurinol, sulfonamides, anticonvulsants, Lamotrigine, Phenobarbital, Phenytoin,
NSAIDs)
TREATMENT
• Post-bone marrow transplantation
• Aim of treatment is to reduce duration of fever, eruption and hospitalization • M. pneumoniae infxn, viral infxn, immunizations
• Systemic corticosteroid use not recommended
• Antibiotics if M. pneumoniae is symptomatic • SLE associated with increased risk
• Oral anti-HSV drugs to prevent recurrences • Radiotherapy

TOXIC EPIDERMAL NECROLYSIS TOXIC EPIDERMAL NECROLYSIS

CLINICAL MANIFESTATIONS OF CUTANEOUS LESIONS CLINICAL MANIFESTATIONS OF CUTANEOUS LESIONS

• Symmetrically distributed on the face, upper trunk and • Advanced eruption showing blisters and epidermal
proximal part of limbs detachment leading to large confluent erosion
• Erythematous, dusky red, purplish macules,
irregularly-shaped which progressively coalesce

• Confluence of necrotic lesions leads to extensive and • Full-blown epidermal necrolysis characterized by large
diffuse erythema erosive areas reminiscent of scalding
• (+) Nikolsky’s sign or dislodgement of epidermis by
lateral pressure
• Lesions evolve to flaccid blisters which spread with
pressure and break easily
TOXIC EPIDERMAL NECROLYSIS TOXIC EPIDERMAL NECROLYSIS
CLINICAL MANIFESTATIONS OF MUCOSAL LESIONS
CLINICAL MANIFESTATIONS OF CUTANEOUS LESIONS
• Classification according to total area of BSA involved in which epidermis is • Begins with erythema followed by painful erosions of the
detached or detachable:
oral, ocular and genital mucosa
• SJS < 10% BSA
• SJS/TEN 10–30% BSA • 80% have conjunctival lesions manifested by pain,
• TEN > 30% BSA photophobia, lacrimation, redness and discharge
• Msy lead to corneal ulceration, anterior uveitis and
purulent conjunctivitis
• Oral cavity and vermillion border feature painful
hemorrhagic erosions coated by grayish white
pseudomembrane and crusts of the lips

TOXIC EPIDERMAL NECROLYSIS TOXIC EPIDERMAL NECROLYSIS

CLINICAL MANIFESTATIONS DIAGNOSIS
• Extracutaneous symptoms:
• High fever • No specific tests to diagnose TEN
• ABG for presence of metabolic derangement
• Pain
• Blood chemistries: electrolytes, serum albumin, protein,
• Weakness creatinine, BUN
• Pulmonary involvement in 25% of pxs: inc RR, cough, • CBC: anemia, thrombocytopenia, neutropenia
may progress to ARDS and ARF
• GIT involvement: less commonly observed, epithelial
necrosis of mucosa manifesting as profuse diarrhea, DIFFERENTIAL DIAGNOSIS
melena, colonic perforation • Erythema multiforme
• Renal involvement: proteinuria, microalbuminuria, • Staphylococcal Scalded Skin Syndrome
hematuria, azotemia, proximal tubule damage • Varicella
• Generalized Bullous Fixed Drug Eruption

TOXIC EPIDERMAL NECROLYSIS ERYTHEMA NODOSUM

TREATMENT PATHOGENESIS
• Early recognition and withdrawal of the offending drug • Hypersensitivity reaction to various etiologic factors
• Supportive care: fluid replacement therapy, room temperature • Early studies have shown the presence of IFNγ and IL-2, activation of
raised to 28℃ to 30℃, use of air-fluidized bed leukocytes and upregulation of various adhesion molecules
• Early nutritional support by NGT
• Aseptic and careful handling ETIOLOGY
• Prophylactic anticoagulation • Infection is the MCC and should be ruled out initially (streptococcal URTI, TB)
• Examine eyes daily. Preservative-free emollients, antibiotics or • Drug allergies (penicillins, sulfonamides, oral contraceptives, bromides and
antiseptic eye drops every 2 hours iodides)
• Malignancies (most often leukemias and lymphomas
• Autoimmunes dss, sarcoidosis and inflammatory bowel disease
 ERYTHEMA NODOSUM ERYTHEMA NODOSUM
CLINICAL MANIFESTATIONS DIAGNOSIS
• Acute onset of tender, painful, erythematous, warm • High ESR
• Suspected streptococcal etiology: (+) throat culture, high ASO titer, leukocytosis
nodules and plaques on the anterior and lateral aspects • Suspected TB: (+) PPD
of both lower legs and ankles • CXR to rule out pulmonary infectious or noninfectious dss
• Other sites may be involved including forearms, thighs
and rarely the trunk or even face DIFFERENTIAL DIAGNOSIS
• May persist a few days or weeks and evolve from an • Cellulitis
• Infection-induced Panniculitis
erythematous or purple-like hue to a bruise-like • Acute Lipodermatosclerosis
pigmentation called erythema contusiforme if
hemorrhage present in the adipose tissue TREATMENT
• Lesions do not ulcerate and resolve w/o atrophy or • Aim of treatment primarily focuses on treatment or removal of the etiologic factor
scarring • Discontinue suspected medications, identify underlying infections, inflammatory
• Systemic symptoms: fever, fatigue, malaise, arthralgia, disorders or malignancies and treat appropriately
• Supportive: bed rest, leg elevation, aspirin, NSAIDs, Supersaturated potassium iodide
arthritis and headache

REITER’S DISEASE REITER’S DISEASE

PATHOGENESIS CLINICAL MANIFESTATIONS
• Postvenereal form favors men (99:1) and occurs primarily in
• Abnormal immune response to an infection probably related to hereditary
the US and Great Britain
susceptibility
• Postdysenteric form favors men (9:1) and occurs primarily in
Asia, continental Europe and North Africa
ETIOLOGY • Mucocutaneous findings consist of balanitis or vulvitis,
keratodermia, stomatitis and nail changes.
• Postvenereal form related to infection with Chlamydia or Ureaplasma • Balanitis (23-50%) a small vesicle appears and later ruptures
urealyticum to form a painless superficial erosion of the coronal margin of
• Postdysenteric form related to Shigella, Salmonella, Yersinia or the prepuce and nearby glans
Campylobacter infection • Keratoderma blenorrhagica (31%) is an erythematous
• May occur in association with AIDS macule that vesiculates, becomes purulent and develops a
thick keratotic cover on soles, toes and glans penis.

REITER’S DISEASE REITER’S DISEASE

CLINICAL MANIFESTATIONS DIAGNOSIS
• Stomatitis painless erythema, vesicles or erosions on the • Mainly based on clinical findings: triad of nongonococcal urethritis, conjunctivitis
palate, tongue, buccal mucosa, lips or gums and arthritis
• Histocompatibility antigens of the B7 cross-reacting group, HLA-B27 are in
• Keratoderma blenorrhagica (31%) is an erythematous majority of patients
macule that vesiculates, becomes purulent and develops a • Elevated CRP, ESR, WBC ct
thick keratotic cover on soles, toes and glans penis.
• Nail involvement consists of subungual hyperkeratosis and a DIFFERENTIAL DIAGNOSIS
thickened, yellow, opaque, ridged, brittle nail plate that may • Peripheral Psoriatic Arthritis
• Rheumatoid Arthritis
shed • Gonococcal Arthritis
• (+) urethritis
• (+) ocular findings: conjunctivitis, iritis, keratitis TREATMENT
• Acute meningoencephalitis, acute psychotic reactions • Diseases not curable and often persists or recurs despite treatment
• Antibiotics for urethral or intestinal infections
• NSAIDs may help with musculoskeletal manifestations
ERYTHEMA AB IGNE ERYTHEMA AB IGNE
PATHOGENESIS CLINICAL MANIFESTATIONS
• Macular dermatosis due to repeated and prolonged nonburning exposure to • Occurrence most often on the legs of women but can occur anywhere in
heat either sex under the appropriate envrionmental circumstances

• A transient reticulated erythema noted initially and after repeated exposure,

ETIOLOGY
• Exposure to infrared radiation
• Local application of heat to relieve pain produces erythema ab igne
• May also occur on the arms of blacksmiths, stokers and cooks
becomes more intense, persists between exposures and a distinctive,
reticulated network of chocolate or golden brown bands develop
• Telangiectasia, epidermal atrophy and scaling may be noted

ERYTHEMA AB IGNE ERYTHEMA DYSCHROMICUM PERSTANS

DIAGNOSIS PATHOGENESIS
• Localization, history of exposure and presence of distinctive reticulated brown • Idiopathic
bands are diagnostic
• Histopathology: thinning of stratum spinosum, effacement of rete ridges, relative
hyperkeratosis, necrotic keratinocytes and vacuolar alteration of the basal cell ETIOLOGY
layer. Dermis is thinned and erythematous, hemosiderin and melanin are found
free and within macrophages in the dermis • Suggested causes and mechanisms: postinflammatory hyperpigmentation,
ammonium nitrate ingestion, whipworm infestation and atmospheric pollutants
DIFFERENTIAL DIAGNOSIS
• Livedo Reticularis

TREATMENT
• Avoid the causative heat source

ERYTHEMA DYSCHROMICUM PERSTANS ERYTHEMA DYSCHROMICUM PERSTANS

CLINICAL MANIFESTATIONS DIAGNOSIS
• Occurs predominantly in people with dark skin but has been reported in • Ash color is the principal feature in making the diagnosis
people with fair complexion • Histopathologic findings: active red border has features of lichen planus and the
• Both sexes affected and has no age predilection pigmented macule resembles postinflammatory hyperpigmentation. The red
border demonstrates a lichenoid dermatitis with vacuolar alteration of the basal
• SIngle to multiple distinctively ash-colored (blue-gray, gray or lead-colored) cell layer
macules of variable size and shape
• Lesions are most commonly noted on the arms, neck, trunk and face but
DIFFERENTIAL DIAGNOSIS
spare the scalp, palms soles and nails
• Erythema Perstans
• Lichen Planus

TREATMENT
• No effective treatment
• Masking with cosmetics may be indicated