Common symptoms may indicate genodermatoses

Washington - When confronted with a patient who presents with unexplained intermittent bouts of fever accompanied by a relatively nondescript rash, dermatologists may find themselves at a loss for a definitive diagnosis, but these may be the telltale signs of an autoinflammatory skin disease at the start of its expression.

"Autoinflammatory diseases are very important to the dermatologist because most patients present with a cutaneous manifestation. Even though the cutaneous manifestations are generally not specific, their morphology, pattern of involvement and histologic features can provide clues in their diagnosis," says Jorge R. Toro, M.D., from the Genetic Epidemiology Branch of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, Rockville, Md.

Dr. Toro says that autoinflammatory diseases are characterized by episodes of seemingly unprovoked inflammation and diseases with inherited recurrent fever that seem to apply to this condition.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is characterized by prolonged episodes of fever and local inflammation.

Patients have been described as having localized myalgias, abdominal pain (in 88 percent of patients) associated with nausea, vomiting, diarrhea or constipation, and conjunctivitis (in 44 percent of patients), as well as erythematous macules and papules (in 40 percent of patients) that progress to erythematous painful patches ranging from 1 cm to 28 cm in diameter. Dr. Toro says that as the erythematous lesions progress, they expand at the periphery, forming annular and serpiginous patches and plaques. He says that approximately 36 percent of cutaneous lesions resolve with an ecchymotic appearance.

"The most common site of these painful lesions is an extremity, where lesions begin proximally, and move within several minutes to several days, distally during the attack. The cutaneous lesions are commonly associated with underlying myalgia that migrates down the extremity in conjunction with the skin lesions, affecting different muscle groups and limiting joint movement during the progression of the attack," Dr. Toro says.

Histologically, TRAPS cannot be differentiated from a viral exanthem or serum-sickness-like reaction. Typically, granulomatous or leukocytoclastic vasculitis, multinucleated macrophages, mast cells or eosinophils are not present.

Dr. Toro says patients with TRAPS generally do not respond to treatment with colchicine. They respond to high-dose corticosteroids, but long-term side effects limit their use.

"Etanercept is effective in reducing, although not in totally eliminating, the clinical and laboratory evidence of inflammation in TRAPS. In addition, interleukin-1 receptor antagonists have been reported to be beneficial in a patient with TRAPS," he says.

Fever, abdominal pain may indicate FMF

Familial Mediterranean fever (FMF) typically presents in childhood or adolescents and is characterized by short attacks (nine to 96 hours) of fever (sometimes a mono symptom), severe abdominal pain (in 95 percent of patients), pleurisy (in 30 percent of patients), monoarticular arthritis (in 75 percent of patients) or an erysipelas-like eruption on the lower extremities.

Frequently, patients can also have purpuric lesions on the face, trunk and extremities.

"The erysipelas-like eruption is the most distinctive cutaneous lesion here and occurs in 3 to 46 percent of patients and in 15 to 20 percent of children. These up-to-15 cm diameter lesions can occur unilaterally or symmetrically below the knee anteriorly, or on the dorsum of the foot," Dr. Toro says.

He adds that reactive systemic amyloidosis is the main complication of the disease. Amyloid deposits are mainly found in the kidneys, but also in the gastrointestinal tract, liver, spleen and, eventually, in the heart, testes and thyroid.

The FMF gene codes for the pyrin protein. Dr. Toro tells Dermatology Times that it was recently demonstrated that the CD2BP1/PSTRIP protein, which is mutated in patients with PAPA syndrome, binds to pyrin, which is the FMF protein. This indicates that FMF and PAPA are disorders of the same pathway.

"Approximately 90 to 95 percent of patients with FMF markedly improve with oral colchicines, and about 75 percent of patients have a complete remission. Colchicine given at 1 mg to 2 mg daily by mouth in adults markedly reduces the frequency and severity of the inflammatory attacks and usually prevents the development of amyloidosis. Therefore, with early diagnosis and treatment with colchicines, FMF usually has a good prognosis," Dr. Toro says.