Juvenile rheumatoid arthritis (JRA) is a generalized systemic disease of unknown etiology characterized by a transient macular, papular, or urticarial rash and ensuing fever, lymphadenopathy (LAD), hepatosplenomegaly (HSM), anemia, and arthralgia.
INSIGHT 
There are four classical evanescent eruptions: (1) urticaria, (2) erythema marginatum (of acute rheumatic fever), (3) the rash of Still’s disease, and (4) serum sickness.
JRA has three major types:
Systemic onset (15%): Still’s disease, fevers, rash, LAD, HSM, serositis, polyarthritis
Polyarticular (35%): Five or more joints: hands, feet > knees/wrists/ankles
Oligo-/Pauciarticular (50%): Four or fewer joints: knees > ankles
SYNONYMS Still’s disease, juvenile idiopathic arthritis, juvenile chronic arthritis.
AGE Peaks: 1 to 4 years; adolescence.
GENDER Systemic JRA: M = F. Others: F > M, 2:1.
PREVALENCE 1/1,000.
GENETICS Polymorphisms for the genes encoding tumor necrosis factor-α (TNF-α), migratory inhibitory factor, interleukin-6 (IL-6), interleukin-10 (IL-10), and TAP genes (transporter of antigenic peptides) have been detected in this patient population. Several HLA alleles have also been associated with the subtypes of JRA, with the strongest genetic associations seen in early-onset pauciarticular JRA.
ETIOLOGY Unknown.
Cytokines TNF-α, migratory inhibitory factor, and IL-6 parallel the fever spikes, but the pathogenesis of JRA is still not understood. JRA tends to be precipitated by emotional, infectious, or surgical stress.
The onset of JRA may be sudden or insidious, depending on the age of the patient (the younger the patient, the more severe the systemic manifestations on average). Cutaneous eruptions occur in 90% of patients and may be the initial presentation. The rash of JRA is evanescent and can be macular or urticarial. Systemically, there may be associated fever, adenopathy, splenomegaly, anemia, and arthralgias.
TYPE Macules, papules, urticarial plaques (Fig. 17-1).
SIZE 2–6 mm to 8–9 cm.
COLOR Salmon pink to red, with a zone of pallor (Fig. 17-2).
DISTRIBUTION Areas of trauma/heat: axilla, waist, olecranon process/ulnar forearm, dorsal hands, knees, ears, scapula, sacrum, buttocks, and heels.
OTHER Palms and soles: thenar and hypothenar eminences may be erythematous. Periungual telangiectasias (5% of patients). Spindling fingers (50%, spindle-shaped deformity of fingers because proximal interphalangeal involvement > distal interphalangeal involvement).
GENERAL FINDINGS Fever > 38.98°C, LAD, HSM.
MUSCULOSKELETAL Arthralgias/arthritis: single joint (knees > ankles/hips > hands), symmetric polyarthritis joints, motion limitation (knees: 90%, fingers: 75%, wrists/ankles: 66%); dactylitis (sausage-appearing swollen digits).
SEROSITIS Pericarditis, pleuritis, or peritonitis.
OTHER Myocarditis, uveitis, CNS involvement.
The diagnosis of JRA is made based on clinical characteristics and history of arthritis lasting for more than 6 weeks, with appropriate studies to exclude other causes such as other autoimmune diseases, other causes of periodic fever, urticaria, rheumatic fever, hypersensitivity reactions, systemic lupus erythematosus (SLE), granuloma annulare, sarcoid, and other granulomatous diseases.
DERMATOPATHOLOGY Edematous collagen fibers, perivascular infiltrate with neutrophils, plasma cells, and histiocytes.
HEMATOLOGY Leukocytosis, anemia, positive rheumatoid factor (80%), elevated erythrocyte sedimentation rate (ESR), low titer ANA positivity, hypoalbuminemia, hyperglobulinemia.
RADIOLOGY Joint destruction in late disease.
The course and prognosis of JRA are variable. The younger the age of onset, the more prominent the systemic manifestations. The rash typically precedes the systemic symptoms by up to 3 years. The disease may end after a few months and never recur, or it may recur after months or years of remission. The disease typically improves by puberty and 85% of patients achieve remission; early treatment may expedite resolution and minimize long-term sequelae. Only 10% have residual severe crippling arthritis which may be associated with a positive rheumatoid factor.
For active disease, symptoms can be relieved with aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, such as indomethacin or naproxen), hydroxychloroquine, and systemic steroids. Anti-TNF drugs (infliximab, etanercept, and adalimumab) have been used, but are less helpful in systemic-onset JRA. For severe cases that are resistant to other therapies, or have crippling deformities, iridocyclitis, or vasculitis, systemic corticosteroids, methotrexate, azathioprine, leflunomide, mycophenolate mofetil, chlorambucil, thalidomide, intravenous immunoglobulin, cyclophosphamide, IL-1/IL-6 receptor antagonists (anakinra, tocilizumab) have been used. For structural correction of severe deformities, surgery is a last resort.
Acute cutaneous lupus erythematosus (ACLE) is the most common cutaneous presentation associated with SLE (Table 17-1). SLE is a serious multisystem disease involving connective tissue and blood vessels; the clinical manifestations include fever (90%); skin lesions (85%); arthritis; and renal, cardiac, and pulmonary disease.
| Acute Cutaneous Lupus Erythematosus (ACLE)—Highly associated with SLE |
| Subacute Cutaneous LE (SCLE)—Variably associated with SLE |
| Chronic Cutaneous LE—Rarely associated with SLE |
| Discoid LE—Uncommonly associated with SLE |
| LE tumidus |
| Lupus panniculitis |
| Chilblain lupus |
| Other variants (bullous, TEN-like, lupus/lichen planus overlap, etc.) |
INSIGHT 
While any organ system may be affected by systemic lupus, the presence of cutaneous lupus erythematosus does not automatically indicate internal organ involvement.
AGE 25% younger than 20 years, peaks: 11 to 13 years, 30 to 40 years.
GENDER Prepubertal: F > M for all ages.
INCIDENCE Prepubertal: rare; adults: 4 in 1,000.
RACE African American, Asian, Latin American >> Caucasian.
GENETICS Family history (<5%) suggests a hereditary component, though environmental factors are believed to play a strong role.
SLE is antibody-mediated, and the trigger for autoantibody production may be multifactorial (genetics, viral or bacterial infection, host tissue response/susceptibility). The production of autoantibodies generates immune complexes targeting body tissues and results in host injury that is non-organ specific, and may differ from person to person.
Up to 80% of patients with SLE have ACLE (malar rash, discoid lesions, photosensitivity, or atrophy), and in 25% of patients, the skin is the first presenting symptom.
TYPE Macules, scale, erosions, atrophic plaques.
COLOR Pink, red, hypo- or hyperpigmentation.
SHAPE Round or oval.
DISTRIBUTION Localized “butterfly” rash on face in light-exposed areas (Fig. 17-3), forearms, dorsa of hands.
HAIR Patchy or diffuse alopecia.
MUCOUS MEMBRANE Ulcers, purpuric necrotic lesions on palate (80%), buccal mucosa, or gums (Fig. 17-4).
OTHER Periungual telangiectasias and palmar erythema are also seen.
LYMPHADENOPATHY (LAD) 50%.
MUSCULOSKELETAL Arthralgia or arthritis (15%).
RENAL Proteinuria, cellular casts (up to 50%).
CARDIAC Pericarditis (up to 20%).
PULMONARY Pleuritis, pneumonitis (up to 20%).
GASTROINTESTINAL Arteritis, peritonitis, hepatomegaly (30%), splenomegaly (20%).
NEUROLOGIC Peripheral neuropathy (14%), CNS disease (10%), seizures, or psychosis (14%).
HEMATOLOGIC Anemia, leukopenia, lymphopenia, thrombocytopenia, elevated ESR.
DERMATOPATHOLOGY Epidermal atrophy, liquefaction degeneration of the dermoepidermal junction, edema of the dermis, dermal inflammatory infiltrate (lymphocytes), and fibrinoid degeneration of the connective tissue and walls of the blood vessels.
OTHER ORGANS Fibrinoid degeneration of connective tissue and walls of the blood vessels associated with an inflammatory infiltrate of plasma cells and lymphocytes.
IMMUNOFLUORESCENCE The lupus band test (direct immunofluorescence) demonstrates IgG, IgM, and C1q granular/globular in a band-like pattern along the dermoepidermal junction. This is positive in lesional skin (90%), sun-exposed areas (80%), and non–sun-exposed areas (50%).
SEROLOGIC Antinuclear antibody (ANA) test positive (>95%), peripheral pattern of nuclear fluorescence and antidouble-stranded DNA antibodies are highly correlated with ACLE.
ACLE can be confused with sunburn, rosacea, drug-induced photosensitivity, eczema, or seborrheic dermatitis. The diagnosis of SLE can be made if four of the following criteria are present based on the American College of Rheumatology criteria:
Malar rash (butterfly appearance)
Discoid rash
Photosensitivity
Oral ulcers
Arthritis
Serositis (pleuritis or pericarditis)
Renal complications (proteinuria or cellular casts)
Neurologic disorder (seizures or psychosis)
Hematologic disorder (anemia, leukopenia, thrombocytopenia)
Immunologic disorder [+lupus erythematosus (LE) prep, anti-DNA, anti-Sm, false + RPR]
ANA (90% of patients have a titer of ≥1:32)
An additional classification system proposed by the Systemic Lupus International Collaborating Clinics in 2012 broadens the diagnostic algorithm for lupus to include 17 possible clinical and immunologic criteria for making the diagnosis.
SLE is a lifelong controllable disease with a survival rate of >90%. Mortality is secondary to renal failure, CNS lupus, cardiac failure, or infection.
ACLE responds best to sun protection and sun avoidance. Topical management includes short courses of high-potency topical or intralesional steroids, calcineurin inhibitors (tacrolimus or pimecrolimus), and retinoids. SLE responds to NSAIDs and salicylates for mild disease (arthritis). More severe disease responds to systemic antimalarials (hydroxychloroquine, chloroquine, quinacrine). The indications for systemic steroids (prednisone, methylprednisolone) include CNS involvement, renal involvement, severely ill patients without CNS involvement, and hemolytic crisis. Antimalarial-resistant disease may require azathioprine, cyclophosphamide, retinoids, thalidomide, mycophenolate mofetil, dapsone, clofazimine, sulfasalazine, or immune response modifiers (rituximab).
Discoid lupus erythematosus (DLE) is a form of chronic cutaneous LE most commonly seen by dermatologists, but is rarely associated with SLE (Table 17-1).
INSIGHT 
Discoid lupus frequently involves the conchal bowl of the ear; lesions present there are highly suggestive of discoid lupus.
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