Group A streptococcus,* tuberculosis,* Yersinia, cat-scratch disease, leprosy, leptospirosis, tularemia, mycoplasma, Whipple disease, lymphogranuloma venereum, psittacosis, brucellosis

OTHER

Sarcoidosis, inflammatory bowel disease,* estrogen-containing oral contraceptives,* systemic lupus erythematosus, Behçet syndrome, severe acne, Hodgkin disease, lymphoma, sulfonamides, bromides, Sweet syndrome, pregnancy, idiopathic*

* Common.

Figure 652-2 Tender red nodules with indistinct borders in a teenage girl with erythema nodosum.

(From Weston AL, Lane AT, Morelli JG: Color textbook of pediatric dermatology, ed 3, St Louis, 2002, Mosby, p 212.)

Erythema Nodosum

Erythema nodosum is a nodular, erythematous hypersensitivity reaction that typically appears with multiple lesions on the exterior surfaces of the arms and legs in the pretibial area (more common) and less often in other cutaneous areas containing subcutaneous fat. The lesions vary in size from 1 to 6 cm, are symmetric, and are oval with the longer axis parallel to the extremity. They initially appear bright or dull red but progress to a brown or purple; they are tense and painful and usually do not ulcerate (see Fig. 652-2). Initial lesions may resolve in 1-2 wk, but new lesions may continue to appear for 2-6 wk. Repeat episodes may occur weeks to months later. Prior to or immediately at the onset of lesions, there may be systemic manifestations that include fever, malaise, arthralgias (50-90%) and rheumatoid factor negative arthritis.

The etiology is unknown in 30-50% of pediatric cases of erythema nodosum; other etiologies are noted in Table 652-1. Group A streptococcal infection and inflammatory disorders (inflammatory bowel disease) are common etiologies in children; sarcoidosis should be considered in young adults.

Treatment includes that of the underlying disease as well as symptomatic relief with nonsteroidal antiinflammatory agents. Salicylates, supersaturated solution of potassium iodide (oral), colchicine, intraintestinal injections of steroidsand, in severe, persistent, or recurrent lesions, oral steroids have been employed. The idiopathic form is a self-limited disorder.

Post-Steroid Panniculitis

Etiology/Pathogenesis

The mechanism of the inflammatory reaction in the fat in post-steroid panniculitis is unknown.

Clinical Manifestations

Fewer than 20 cases of post-steroid panniculitis have been reported, with most of these being in children. The disorder occurs in children who have received high-dose corticosteroids. In 1-2 wk after discontinuation of the drug, multiple subcutaneous nodules usually appear on the cheeks, although other areas may be involved. Nodules range in size from 0.5 to 4 cm, are erythematous or skin colored, and may be pruritic.

Histology

A lobular panniculitis with a mixed infiltrate of lymphocytes, histiocytes, and neutrophils is seen. Scattered swollen adipocytes with eosinophilic, needle-shaped crystals are also seen. The epidermis, dermis, and fibrous septa of the fat are normal. Vasculitis is not seen.

Treatment

Treatment of post-steroid panniculitis is unnecessary because the lesions remit spontaneously over a period of months without scarring.

Lupus Erythematosus Profundus (Lupus Erythematosus Panniculitis)

Etiology/Pathogenesis

It is unknown what separates those patients in whom lupus erythematosus profundus develops from other patients with systemic lupus erythematosus. This variant of lupus erythematosus is rare in childhood.

Clinical Manifestations

Lupus erythematosus profundus manifests as one to several firm, well-defined, purple plaques or nodules 1 to 3 cm in diameter, most commonly on the face, buttocks, or proximal extremities. This condition may occur in patients with systemic or discoid lupus erythematosus and may precede or follow the development of other cutaneous lesions. The overlying skin is usually normal but may be erythematous, atrophic, poikilodermatous, or hyperkeratotic (Fig. 652-3). Lesions may be painful and may ulcerate. On healing, a shallow depression generally remains or, rarely, soft pink areas of anetoderma result.

Figure 652-3 Deep nodule of lupus profundus with overlying hyperkeratotic lesion of discoid lupus erythematosus.

Histology

The histopathologic changes in lupus erythematosus profundus are distinctive and may allow the clinician to make the diagnosis in the absence of other cutaneous lesions of lupus erythematosus. The panniculitis is characterized by a mostly lobular dense infiltrate of lymphocytes and plasma cells. A dense perivascular and periappendigeal lymphocytic infiltrate is seen in the dermis. Lichenoid changes may be identified at the epidermal-dermal junction. Histopathologic differentiation from subcutaneous panniculitis–like T-cell lymphoma may be difficult. Results of lupus band and antinuclear antibody tests are usually positive.

Treatment

Nodules tend to be persistent. Hydroxychloroquine (2-5 mg/kg/day) is the treatment of choice for lupus erythematosus profundus. Intralesional corticosteroids may worsen the residual lipoatrophy. Immunosuppressive agents are indicated only for treatment of other severe manifestations of systemic lupus erythematosus. Avoidance of sun exposure and trauma is also important.

α₁-Antitrypsin Deficiency

Etiology/Pathogenesis

Individuals with α₁-antitrypsin deficiency have severe homozygous deficiency or, rarely, a partial deficiency of the protease inhibitor α₁-antitrypsin, which inhibits trypsin activity and the activity of elastase, serine proteases, collagenase, factor VIII, and kallikrein (Chapter 385). Panniculitis occurs with the Z subtype.

Clinical Manifestations

Cellulitis-like areas or tender, red nodules occur on the trunk or proximal extremities (Chapter 385). Nodules tend to ulcerate spontaneously and discharge an oily yellow fluid. Panniculitis may be associated with other manifestations of the disease, such as panacinar emphysema, noninfectious hepatitis, cirrhosis, persistent cutaneous vasculitis, cold contact urticaria, and acquired angioedema. Diagnosis can be substantiated by a decreased level of serum α₁-antitrypsin activity.

Histology

Extensive septal and lobular lymphocytic infiltrate with necrosis of the fat is observed.

Treatment

Treatment of the panniculitis in with α₁-antitrypsin deficiency is part of the overall treatment of the disease (Chapter 385).

Pancreatic Panniculitis

Etiology/Pathogenesis

Pathogenesis of pancreatic panniculitis appears to be multifactorial, involving liberation of the lipolytic enzymes lipase, trypsin, and amylase into the circulation, causing adipocyte membrane damage and intracellular lipolysis. There is no correlation, however, between the occurrence of panniculitis and the serum concentration of pancreatic enzymes.

Clinical Manifestations

Pancreatic panniculitis manifests most commonly on the pretibial regions, thighs, or buttocks as tender, erythematous nodules that may be fluctuant and occasionally discharge an oily yellowish substance. It appears most often in males with alcoholism but may also occur in patients with pancreatitis as a result of cholelithiasis or abdominal trauma, with rupture of a pancreatic pseudocyst, with pancreatic ductal adenocarcinoma, or with pancreatic acinar cell carcinoma. Associated features may include polyarthritis (PPP [pancreatitis-panniculitis-polyarthritis] syndrome). In almost 65% of patients, abdominal signs are absent or mild, making the diagnosis difficult.

Histology

Microscopic changes consist of multiple foci of fat necrosis that contain ghost cells with thick, shadowy walls and no nuclei. A polymorphous inflammatory infiltrate surrounds the areas of fat necrosis.

Treatment

The primary pancreatic disorder must be treated. The arthritis may be chronic and responds poorly to treatment with nonsteroidal anti-inflammatory drugs and oral corticosteroids.

Subcutaneous Fat Necrosis

Etiology/Pathogenesis

The cause of subcutaneous fat necrosis is unknown. The disease in infants may be due to ischemic injury under various circumstances, such as maternal preeclampsia, birth trauma, asphyxia, and prolonged hypothermia; in many affected infants, however, provocative factors are not identified. Susceptibility has been attributed to differences in composition between the subcutaneous tissue of young infants and that of older infants, children, and adults. Neonatal fat solidifies at a relatively high temperature because of its relatively greater concentration of high–melting point saturated fatty acids, such as palmitic and stearic acids.

Clinical Manifestations

This inflammatory disorder of adipose tissue occurs primarily in the first 4 wk of life in full-term or post-term infants. Typical lesions are asymptomatic, rubbery to firm, erythematous to violaceous plaques or nodules on the cheeks, buttocks, back, thighs, or upper arms (Fig. 652-4). Lesions may be focal or extensive and are generally asymptomatic, although they may be tender during the acute phase. Uncomplicated lesions involute spontaneously within weeks to months, usually without scarring or atrophy. Calcium deposition may occasionally occur within areas of fat necrosis, which may sometimes result in rupture and drainage of liquid material. A rare but potentially life-threatening complication is hypercalcemia. It manifests at 1-6 mo of age as lethargy, poor feeding, vomiting, failure to thrive, irritability, seizures, shortening of the QT interval on electrocardiography, or renal failure. The origin of the hypercalcemia is unknown.