Lupus Erythematosus

Lupus erythematosus (LE; Chapter 152) is an idiopathic autoimmune inflammatory disease that may be multisystemic or confined to the skin.

Systemic Lupus Erythematosus

Systemic LE (SLE) is a chronic inflammatory multisystem disease. It is a diagnosed when 4 of 11 well-defined criteria are present (Chapter 152). Three of the criteria are skin findings. Criterion 1 is the classic malar or “butterfly” rash (Fig. 637-1). It must be distinguished from other causes of a “red face,” most notably seborrheic dermatitis, atopic dermatitis, and rosacea. Criterion 2 is a discoid rash. Criterion 3 is a photosensitive erythematous macular or papular eruption (Fig. 637-2). Other associated but not diagnostic cutaneous findings include purpuric lesions, livedo reticularis, mucosal ulcerations, Raynaud phenomenon, and nonscarring alopecia.

Figure 637-1 Malar rash of systemic lupus erythematosus (SLE).

Figure 637-2 Photosensitive rash of systemic lupus erythematosus (SLE).

Cutaneous LE demonstrates varying degrees of epidermal atrophy, plugging of hair follicles, and a vacuolar alteration at an inflamed dermal-epidermal junction. Deposition of immunoglobulins (IgM, IgG) and complement in lesional skin may help confirm the diagnosis. Immune deposits in nonlesional sun-exposed skin are found in the majority of patients with SLE (lupus band test). Treatment of skin lesions includes sun protection and low- to mid-potency topical corticosteroids.

Neonatal Lupus Erythematosus

Neonatal LE (NLE; Chapter 152.1) manifests during the 1st weeks to months of life as annular, erythematous, scaly plaques, typically on the head, neck, and upper trunk (Fig. 637-3). Ultraviolet light may exacerbate or initiate cutaneous lesions. NLE is often misdiagnosed as infantile eczema, seborrheic dermatitis, or tinea corporis. Passive transfer of maternal IgG (anti-Ro/La, SS-A/SS-B) antibodies causes the transient skin lesions; antibody levels wane by 6 mo, generally resulting in clearance of the rash. Congenital heart block occurs in 30% of affected infants, but only 10% of affected infants have both skin and cardiac abnormalities. Noncardiac extracutaneous manifestations, such as anemia, thrombocytopenia, and cholestatic liver disease, are uncommon. Maternal antibody (antinuclear antibody [ANA]) testing is indicated.

Figure 637-3 Annular plaque in neonatal lupus erythematosus (NLE).

Discoid Lupus Erythematosus

Discoid LE (DLE) is uncommon in early childhood and manifests in late adolescence. The signature skin findings in DLE are chronic, erythematous, scaly, atrophic, telangiectatic plaques (Fig. 637-4) on sun-exposed skin that frequently heal with scarring and dyspigmentation. Extracutaneous features may include involvement of the nasal and oral mucosa, eyes, and nails. The differential diagnosis includes other photodermatoses, such as polymorphous light eruption, juvenile springtime eruption, and juvenile dermatomyositis. There is a distinct overlap between SLE and DLE, with common histopathologic features and photoexacerbation; most patients with DLE have normal laboratory results and do not progress to systemic disease. Topical sunscreens and steroids may be helpful. Intralesional steroids and oral antimalarials (hydroxychloroquine) are used for severe disease.

Figure 637-4 Erythematous scaly plaque of discoid lupus erythematosus (DLE).

Juvenile Dermatomyositis

Characteristic skin findings are often the presenting sign of juvenile dermatomyositis (JDMS; Chapter 153). An ill-defined, erythematous to violaceous, scaly, minimally pruritic eruption occurs in photodistributed areas such as the face, upper trunk, and extensor extremities. Circumscribed periocular involvement of this heliotrope rash may take the appearance of “raccoon eyes,” particularly in young children. Distinctive papules overlying the knuckles (Gottron papules) are helpful in suggesting the diagnosis in the absence of associated muscle weakness (Fig. 637-5). Other cutaneous features include nail fold and gingival margin telangiectasia, palmar hyperkeratosis (“mechanic’s hands”), and a poikilodermatous (dyspigmentation and telangiectasia) eruption over the shoulder girdle (“shawl sign”). Cutaneous features may precede the systemic illness. The differential diagnosis includes atopic dermatitis, other connective tissue diseases, lichen planus, medication reactions, and infectious exanthems. The paucity of itch in JDMS may help eliminate some diagnostic considerations. Lesional skin demonstrates epidermal atrophy and vacuolar degeneration at the dermal-epidermal junction. JDMS is distinct from adult dermatomyositis in both presentation and prognosis. Pediatric patients have more difficulty with gastrointestinal vasculopathy and cutaneous calcifications but are not at increased risk of malignancy.

Figure 637-5 Gottron papules in juvenile dermatomyositis.

Treatment includes systemic steroidal and nonsteroidal immunosuppressants, intravenous immunoglobulin, anti-tumor necrosis factor (TNF) agents, and anti-CD20 monoclonal antibodies; topical photoprotection is vital to prevent cutaneous exacerbations.

Progressive Systemic Sclerosis

Progressive systemic sclerosis frequently manifests as acral (sclerodactyly, ulceration, nail fold telangiectasia, or Raynaud phenomenon) and other cutaneous changes (pinched nose, furrowed perioral skin, or “scleroderma facies”) (Chapter 154). Overlap syndromes, such as CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias) and mixed connective tissue disease, may include some physical and laboratory features of scleroderma.

Henoch-Schönlein Purpura (IgA Vasculitis)

Henoch-Schönlein purpura (HSP) is a vasculitis that manifests as purpuric lesions prominently on the buttocks and lower extremities of school-aged children (Fig. 637-6). Infantile hemorrhagic edema (IHE; also called acute hemorrhagic edema of infancy) shares some clinical features with HSP but appears in infants and toddlers. IHE is characterized by circumscribed purpuric papules and plaques on the trunk and extremities but, unlike HSP, commonly affects the face and lacks other organ involvement. IHE may follow a recent infection and manifests as peripheral edema and fever; patients with HSP are usually afebrile. HSP must also be differentiated from infectious causes of purpuric skin lesions, such as meningococcemia, Rocky Mountain spotted fever, and purpuric viral exanthems such as those caused by enteroviruses, as well as from juvenile rheumatoid arthritis and other vasculitides. Diagnosis is confirmed by vasculitis with the immunofluorescence finding of IgA in the blood vessel walls.

Figure 637-6 Purpura of the lower leg in Henoch-Schönlein purpura (HSP).

Kawasaki Disease

Kawasaki disease (Chapter 160) is a clinical diagnosis based on both cutaneous and extracutaneous features. The skin eruption of Kawasaki disease may be polymorphic, manifesting variously as urticarial, maculopapular, or morbilliform patches and plaques on the trunk and extremities, but early involvement with erythema and peeling in the perineum/inguinal region may be an initial clue to the diagnosis. Acral edema and desquamation are also prominent features but typically occur later. Conjunctivitis (nonpurulent), often with sparing of the limbus, and lingual plaques (“white strawberry tongue”) that shed to produce denuded, erythematous patches with prominent papilla (“strawberry tongue”) are classic mucocutaneous features.

Behçet Disease

Behçet disease (Chapter 155) is multisystem disease that includes oral and genital ulceration and ocular disease (uveitis, relapsing iridocyclitis). Recurrent aphthous stomatitis is present in almost all patients and is commonly the presenting symptom. Genital ulcerations may resemble aphthae, can occur on the penis or scrotum, and may be particularly painful in females. Additional skin findings may include folliculitis, purpuric lesions, erythema nodosum, and pustule formation after venipuncture or skin trauma (pathergy). Differential diagnosis of oral lesions includes recurrent aphthous stomatitis, herpes simplex, and less common oculocutaneous syndromes (e.g., MAGIC [mouth and genital ulcers with inflamed cartilage] syndrome). Skin biopsy demonstrates nongranulomatous vasculitis in all vessel sizes. Oral lesions may respond to swish and spit/swallow preparations variably including corticosteroids, antihistamines, antibiotics, and analgesics.

Inflammatory Bowel Disease

Up to 30% of patients with ulcerative colitis (Chapter 328.1) present with cutaneous manifestations. Aphthous ulcers are common and may worsen with gastrointestinal exacerbations. Erythema nodosum, occurring in up to 10% of patients, manifests as warm, erythematous nodules, often on the distal lower extremities. Pyoderma gangrenosum is a focal, ulcerative process that has distinctive, inflamed, undermined borders and a purulent, boggy center. Thrombophlebitis also occurs at an increased rate in patients with ulcerative colitis. In most cases, treatment of the underlying disease state improves the cutaneous sequelae.

Crohn disease, or regional enteritis (Chapter 328.2), classically manifests as perianal fissures and skin tags, abscesses, sinuses, and fistulas; these may be presenting signs. As in ulcerative colitis, aphthae, erythema nodosum, and pyoderma gangrenosum occur at increased frequency and may improve with treatment of the underlying disease. Noncaseating granulomatous inflammation is seen on routine histopathology, and when found in skin not contiguous with the intestinal tract, is labeled metastatic Crohn disease. Metastatic lesions may appear as solitary or multiple, localized plaques or nodules and may be located on perianal, perioral, or other cutaneous surfaces, including scars and ileostomy sites. Standard therapy includes immunosuppressive medications, anti-TNF agents, anti-CD20 monoclonal antibodies, nutritional support, and surgery for complications.

Sweet Syndrome

Also known as acute febrile neutrophilic dermatosis, Sweet syndrome (Chapter 161.5) manifests abruptly as tender, erythematous, edematous plaques or nodules on any area of the skin, often accompanied by fever, anemia, and leukocytosis. Diagnosis is confirmed by the presence of a dense neutrophilic infiltrate without evidence of vasculitis. The differential diagnosis includes pyoderma gangrenosum, cellulitis, erythema multiforme, Behçet disease, and erythema nodosum. The etiology of Sweet syndrome is unknown but may involve a hypersensitivity reaction to a bacterial, viral, or tumor antigen. Forty-two percent of cases of Sweet’s syndrome in childhood occur without an identifiable etiology. The other 58% have been associated with recurrent multifocal osteomyelitis, vasculitis with aortitis, recurrent infection due to immunodeficiency, arthritis, SLE, aplastic anemia, Fanconi anemia, and leukemia. Sweet syndrome is sensitive to oral corticosteroids.

Necrolytic Migratory Erythema

Necrolytic migratory erythema (NME), or glucagonoma syndrome, is a distinctive migratory erythema that often signals an underlying neoplasm, usually an α-cell pancreatic tumor. Polycyclic erythematous patches and plaques on the trunk, extremities, and groin occur in association with glossitis and cheilitis. Elevated glucagon levels, glucose intolerance, and hypoaminoacidemia confirm the diagnosis, and tumor resection leads to resolution of the rash.

Other cutaneous findings that may signal an underlying malignancy include pruritus, ichthyosis, acanthosis nigricans, urticaria, pemphigus, and erythroderma.

Medication Reactions

The majority of medication reactions are mild morbilliform or exanthematous eruptions of little clinical consequence. Identifying the suspect medication may be difficult owing to the many medications used in immunosuppressed patients. Features that may help identify suspect medications include rash onset relative to exposure, character of distribution and spread, associated symptoms, and laboratory data. Medication eruptions begin on the trunk 7-10 days after exposure; they spread peripherally and are associated with pruritus and, less commonly, with fever, arthralgia, and lymphadenopathy. Eosinophilia may support a diagnosis of drug eruption but may be absent in the setting of bone marrow suppression. Penicillins, sulfa drugs, cephalosporins, nonsteroidal anti-inflammatory drugs, anticonvulsants, and, on occasion, aminoglycosides are common offenders. Medication eruptions may resolve despite continued use of the offending agent, or they may progress to more severe involvement. A careful drug history, elimination of all nonessential, suspect medications or change to medications of dissimilar class, and treatment of pruritus with emollients, topical steroids, antihistamines, and antipruritics are indicated. Skin biopsies are rarely useful in distinguishing medication eruptions from infectious exanthems, although GVHD, if sufficiently advanced, may have signature histopathologic findings.

Graft versus Host Disease

GVHD (Chapter 131) may have florid cutaneous expression in addition to characteristic extracutaneous features such as fever, mucositis, diarrhea, and hepatitis. It may be either acute or chronic. Acute GVHD occurs in 35-50% of hematopoietic stem cell transplants and may be mistaken for a medication reaction or infectious exanthem, on the basis of the nonspecific erythematous maculopapular eruption that often starts focally and generalizes. Features that may suggest GVHD include timing of eruption (typically 1-3 wk after transplantation, at the time of hematopoietic reconstitution), initial involvement of the head and neck including the ears, and subsequent spread to the trunk, extremities, palms, and soles. Chronic GVHD, which occurs in ≈20% of long-term transplant survivors, is seen most often in patients who have previously experienced acute GVHD. About 50% of patients with acute GVHD eventually have chronic GVHD. Cutaneous manifestations of chronic GVHD are distinctive, with sclerotic, dyspigmented scaly plaques and lichenoid papules predominating (Fig. 637-7). Treatment includes systemic immunosuppression supplemented by topical steroids, topical immunomodulators, antihistamines, antipruritics, and emollients. Chronic disease may also respond to pentostatin, mycophenolate mofetil, photochemotherapy (PUVA), UVA-1, and plasmapheresis. GVHD may also develop in susceptible patients who have not undergone transplantation, such as the severely immunosuppressed neonate or infant in response to therapeutic transfusion of nonirradiated blood products, the fetus with congenital immunodeficiency and with transplacental passage of maternal lymphocytes, as well as the older child with malignancy who has received nonirradiated blood products.

Figure 637-7 Lichenoid eruption in chronic graft versus host disease (GVHD).