• Among the major types of juvenile idiopathic arthritis (JIA; formerly juvenile rheumatoid arthritis [JRA]), cutaneous manifestations are most common in SoJIA, psoriatic arthritis (see Chapter 6), and rheumatoid factor (RF)-positive polyarthritis (rheumatoid nodules and other findings similar to rheumatoid arthritis [RA]; see below).

• SoJIA can develop at any age prior to 16 years and affects both sexes equally; AoSD has peaks in the second and fourth decades and affects women more often than men.

• Both SoJIA and AoSD are characterized by daily spiking fevers (especially in the late afternoon/early evening) accompanied by an evanescent eruption of salmon-pink macules and slightly edematous papules and plaques (Fig. 37.1A,B); these lesions are usually asymptomatic and favor sites of pressure or trauma, often occurring in a linear array.

• Less common skin findings include periorbital edema and persistent pruritic papules and plaques that are scaly, violaceous to reddish brown in color, and linear in configuration (Fig. 37.1C).

• Additional features include a prodromal sore throat and arthralgias/myalgias, arthritis (usually polyarticular; ± carpal ankylosis in AoSD), lymphadenopathy, hepatosplenomegaly, and serositis; occasionally patients may develop macrophage activation syndrome (also characterized by markedly elevated ferritin).

• Leukocytosis with neutrophilia, thrombocytosis, anemia, elevated ESR/CRP, and extremely high serum ferritin levels (e.g. >4000 mg/ml) are common laboratory findings, whereas ANA and RF are usually absent.

• DDx: infections (e.g. parvovirus B19), rheumatic fever, serum sickness-like reactions, urticarial vasculitis, Schnitzler’s syndrome (in adults; see Chapter 14), other autoimmune connective tissue diseases, hereditary periodic fever syndromes (see Table 3.2).

• Rx: NSAIDs (for mild disease), systemic CS, methotrexate, antagonists of IL-1 (e.g. anakinra, canakinumab) or IL-6 (e.g. tocilizumab), and TNF inhibitors (the latter especially for arthritis).

• Chronic inflammatory disorder characterized primarily by destructive arthritis.

• Affects 1–3% of adults, with a female : male ratio of 2–3 : 1 and a peak onset between 35 and 60 years of age.

• RF and anti-cyclic citrullinated peptide (CCP) antibodies represent serologic markers of RA.

• Cutaneous manifestations of RA are presented in Table 37.1 and Fig. 37.2; these findings can serve as diagnostic clues or signs of serious systemic disease.

• Two clinicopathologic patterns of granulomatous dermatitis that occur in patients (women > men) with RA and other autoimmune disorders.

• IGD presents as annular erythematous plaques or linear cords (‘rope sign’) that favor the lateral and upper trunk, axillae, medial thighs, and buttocks (Fig. 37.3); patients often have RA or seronegative arthritis.

• PNGD presents as skin-colored to erythematous, umbilicated papulonodules that are often crusted and favor the elbows (see Fig. 19.11B) and extensor hands/fingers; associated with RA, SLE, and ANCA-positive systemic vasculitides (e.g. Churg–Strauss syndrome).

• Because interstitial granulomatous drug reactions can have clinical and histologic features similar to those of IGD and PNGD, a review of all medications should be performed; culprit drugs include calcium channel blockers, angiotensin-converting enzyme inhibitors, statins, and TNF inhibitors.

• Histologically, a dense pandermal infiltrate is seen in both entities; IGD features rosettes of palisading histiocytes surrounding tiny foci of degenerated collagen, while findings in PNGD range from a predominance of neutrophils with foci of leukocytoclastic vasculitis to well-developed palisaded granulomas surrounding basophilic degenerated collagen.

• DDx: interstitial granulomatous drug reaction (see above); for IGD – patch-type granuloma annulare (GA), morphea (inflammatory stage), mycosis fungoides and leprosy; for PNGD – papular GA, rheumatoid nodules/nodulosis, perforating disorders.

• Rx: high-potency topical or intralesional CS, dapsone (if prominent neutrophils); may improve with treatment of the underlying disorder.

• Autoimmune disorder primarily affecting the lacrimal and salivary glands, resulting in xerophthalmia and xerostomia; may coexist with other AI-CTDs (e.g. LE).

• Affects ~0.5% of the general population, with a female : male ratio of 9 : 1; peak onset is in the fourth and fifth decades of life, but can occur at any age.

• Cutaneous manifestations include xerosis, palpable purpura due to small vessel vasculitis (including cryoglobulinemic vasculitis), hypergammaglobulinemic purpura of Waldenström, urticarial vasculitis, annular erythema, and Raynaud’s phenomenon.

• Additional features can include vaginal dryness, arthritis, peripheral neuropathy, internal organ involvement (e.g. kidneys), and development of B-cell lymphoma (often extranodal marginal zone).

• Majority of patients have anti-Ro/SS-A and anti-La/SS-B antibodies, a positive RF, and an elevated ESR.

• Diagnostic criteria for Sjögren’s syndrome are presented in Table 37.2.

• Rx: mostly symptomatic – use of artificial tears and saliva (e.g. methylcellulose drops), chewing sugar-free gum, meticulous dental hygiene, and treatment of superimposed oral candidiasis; sicca symptoms may improve with cyclosporine eye drops or muscarinic receptor agonists (e.g. pilocarpine), and vasculitis or internal involvement often require systemic CS, conventional immunosuppressive agents, or rituximab.

• Uncommon autoimmune condition that affects cartilaginous structures; pathogenesis is thought to involve a reaction against type II collagen.

• Most patients develop erythema, swelling and pain of the cartilaginous portion of the auricle, with sparing of the earlobe (Fig. 37.4A).

• Other manifestations include cutaneous small vessel vasculitis (Fig. 37.4B), aphthae (oral or genital; may overlap with Behçet’s disease), nasal chondritis (potentially producing a saddle nose deformity), involvement of cartilage of the respiratory tract (e.g. larynx, trachea, bronchi) and costochondral junctions, arthritis, ocular inflammation, audiovestiblar damage, and myelodysplastic syndrome.

• DDx: early phase – erysipelas, cellulitis, infectious chondritis or zoster; nasal destruction – Wegener’s granulomatosis, nasal natural killer/T-cell lymphoma, infections (e.g. mucocutaneous leishmaniasis) (see Table 19.3).

• Rx: prednisone (for acute flares), dapsone, immunosuppressive agents, TNF inhibitors; surgical repair of damaged cartilaginous structures.

• Characterized by high-titer anti-U1 ribonucleoprotein (U1-RNP) antibodies plus a constellation of clinical features including arthritis, myositis, and findings of systemic sclerosis; the latter range from swollen hands and Raynaud’s phenomenon to esophageal dysmotility and pulmonary hypertension (the most serious complication) or fibrosis (often mild).

• Favors women (female : male ratio ~9 : 1) in the second and third decades of life.

• Edema and erythema of the digits is an early manifestation; digital infarcts, periungual telangiectasias with dropout areas, sclerodactyly, and calcinosis cutis may also develop.

• Poikiloderma on the upper trunk and proximal extremities is common; photosensitivity, malar erythema, and subacute cutaneous LE occasionally occur.

• DDx: features overlap with those of systemic sclerosis, dermatomyositis/polymyositis, and SLE; for this reason, the debate continues regarding the distinction between MCTD (a specific entity requiring the presence of elevated U1-RNP) and less specific ‘overlap syndromes’ (features of two or more AI-CTDs in a single patient).

• Rx: varies depending on the organs involved and disease severity.

• Among the major types of juvenile idiopathic arthritis (JIA; formerly juvenile rheumatoid arthritis [JRA]), cutaneous manifestations are most common in SoJIA, psoriatic arthritis (see Chapter 6), and rheumatoid factor (RF)-positive polyarthritis (rheumatoid nodules and other findings similar to rheumatoid arthritis [RA]; see below).

• SoJIA can develop at any age prior to 16 years and affects both sexes equally; AoSD has peaks in the second and fourth decades and affects women more often than men.

• Both SoJIA and AoSD are characterized by daily spiking fevers (especially in the late afternoon/early evening) accompanied by an evanescent eruption of salmon-pink macules and slightly edematous papules and plaques (Fig. 37.1A,B); these lesions are usually asymptomatic and favor sites of pressure or trauma, often occurring in a linear array.

• Less common skin findings include periorbital edema and persistent pruritic papules and plaques that are scaly, violaceous to reddish brown in color, and linear in configuration (Fig. 37.1C).

• Additional features include a prodromal sore throat and arthralgias/myalgias, arthritis (usually polyarticular; ± carpal ankylosis in AoSD), lymphadenopathy, hepatosplenomegaly, and serositis; occasionally patients may develop macrophage activation syndrome (also characterized by markedly elevated ferritin).

• Leukocytosis with neutrophilia, thrombocytosis, anemia, elevated ESR/CRP, and extremely high serum ferritin levels (e.g. >4000 mg/ml) are common laboratory findings, whereas ANA and RF are usually absent.

• DDx: infections (e.g. parvovirus B19), rheumatic fever, serum sickness-like reactions, urticarial vasculitis, Schnitzler’s syndrome (in adults; see Chapter 14), other autoimmune connective tissue diseases, hereditary periodic fever syndromes (see Table 3.2).

• Rx: NSAIDs (for mild disease), systemic CS, methotrexate, antagonists of IL-1 (e.g. anakinra, canakinumab) or IL-6 (e.g. tocilizumab), and TNF inhibitors (the latter especially for arthritis).

• Chronic inflammatory disorder characterized primarily by destructive arthritis.

• Affects 1–3% of adults, with a female : male ratio of 2–3 : 1 and a peak onset between 35 and 60 years of age.

• RF and anti-cyclic citrullinated peptide (CCP) antibodies represent serologic markers of RA.

• Cutaneous manifestations of RA are presented in Table 37.1 and Fig. 37.2; these findings can serve as diagnostic clues or signs of serious systemic disease.

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