Relapsing Polychondritis

Relapsing polychondritis (RP) is a rare condition characterized by episodic cartilage inflammation causing cartilage destruction and deformation in the external ears, nose, larynx, and tracheobronchial tree. Antibodies to native type II collagen are present in about a third of patients with RP, suggesting that an autoimmune reaction to this protein plays a role in its pathogenesis. RP may coexist with other autoimmune diseases, such as systemic lupus erythematosus. Patients may experience oligoarthritis or polyarthritis, uveitis, and hearing loss due to inflammation near the auditory and vestibular nerves. Children may initially relate only episodes of intense erythema over the outer ears. Cardiac involvement, including pericarditis and conduction defects, has been reported. Diagnostic criteria established for adults are useful guidelines for evaluating children with suggestive symptoms (see Table 163-1 on the Nelson Textbook of Pediatrics website at www.expertconsult.com). The differential diagnosis includes Wegener granulomatosis (Chapter 161.4) and Cogan syndrome, which is characterized by auditory nerve inflammation and keratitis but not chondritis. The clinical course of RP is variable, and flares may remit spontaneously. Flares of disease are often associated with elevations of erythrocyte sedimentation rate (ESR). Many cases respond to nonsteroidal anti-inflammatory drugs, but some require corticosteroids or other immunosuppressive agents (azathioprine, methotrexate, hydroxychloroquine, colchicine, cyclophosphamide, cyclosporine, and anti–tumor necrosis factor [TNF] agents), as reported in small series and case reports. Severe, progressive, and potentially fatal disease resulting from destruction of the tracheobronchial tree and airway obstruction is unusual in childhood.

Table 163-1 EMPIRIC DIAGNOSTIC CRITERIA FOR RELAPSING POLYCHONDRITIS*

* The diagnosis is established by the presence of 2 major criteria or of 1 major and 2 minor criteria. Histologic examination of affected cartilage is not required.

From Michet CJ Jr, McKenna CH, Luthra HS, et al: Relapsing polychondritis: survival and predictive role of early disease manifestations, Ann Intern Med 104:74–78, 1986.

Mucha-Habermann Disease

Febrile ulceronecrotic Mucha-Habermann disease, also referred to as pityriasis lichenoides et varioliformis acuta (PLEVA), is a cutaneous vasculitis characterized by episodes of macules, papules, and papulovesicular lesions that can develop central ulceration, necrosis, and crusting. It exhibits a male preponderance (3 : 1) and occurs more frequently in younger age groups. Oral, genital, and conjunctival mucosae may be involved. Arthritis and high fever, with an elevated ESR, can occur. The diagnosis is confirmed by biopsy of skin lesions that reveal perivascular and intramural lymphocytic inflammation affecting capillaries and venules in the upper dermis that may lead to keratinocyte necrosis. When disease is severe, corticosteroids have been used with questionable effect, and methotrexate has been reported to induce rapid remission in resistant cases. Cyclosporine and anti-TNF agents have been used in case reports. PLEVA has been associated with increased mortality in adults but not in children.

Sweet Syndrome

Sweet syndrome, or acute febrile neutrophilic dermatosis, occurs most often in young women. It is characterized by fever, elevated neutrophil count, and raised, tender erythematous plaques over the face, extremities, and trunk (Table 163-2). Some children also have arthritis. The syndrome may be idiopathic or secondary to malignancy (particularly acute myelogenous leukemia), drugs (granulocyte-colony stimulating factor), or rheumatic diseases (Behçet disease, antiphospholipid antibody syndrome, systemic lupus erythematosus). Skin biopsy reveals neutrophilic perivascular infiltrates in the upper dermis. The condition usually responds to treatment with corticosteroids.

Table 163-2 DIAGNOSTIC CRITERIA FOR CLASSIC SWEET SYNDROME*

* The diagnosis is established by the presence of 2 major criteria plus 2 of the 4 minor criteria.

From Cohen PR: Sweet’s syndrome—a comprehensive review of an acute febrile neutrophilic dermatosis, Orphanet J Rare Dis 2:34, 2007.

Hypertrophic Osteoarthropathy

Children with chronic disease, especially pulmonary or cardiac disease, may demonstrate clubbing of the terminal phalanges, especially of the fingers, with associated hypertrophic osteoarthropathy of the distal interphalangeal joints, as well as tender periosteal new bone formation along tubular long bones and bones of the hand. Hypertrophic osteoarthropathy is found in children with chronic pulmonary disease (cystic fibrosis), congenital heart disease, gastrointestinal disease (malabsorption syndromes, biliary atresia, inflammatory bowel disease), and malignancies (nasopharyngeal sarcoma, osteosarcoma, Hodgkin disease) and may precede diagnosis of cardiopulmonary disease or malignancy. Although the cause is unknown, studies suggest that platelet precursors fail to fragment into platelets within the pulmonary vascular bed before entering the systemic circulation. Platelet fragments are trapped in the peripheral vasculature and interact with peripheral endothelial cells, resulting in release of platelet-derived growth factor and vascular endothelial growth factor, which induces proliferation of vascular endothelial cells, smooth muscle cells, and fibroblasts. Symptoms often improve if the underlying condition can be treated successfully. Persistent cases reportedly respond to pamidronate (1 mg/kg intravenously to a maximum of 60 mg) or octreotide in adults (100 µg subcutaneously twice daily). Evaluation of children presenting with hypertrophic osteoarthropathy should include a chest radiograph to check for pulmonary disease or an intrathoracic mass.