Early-onset symptomatic emphysema has been described to occur in susceptible individuals under age 50. Herein, we describe a 48-year-old smoker with severe panlobular emphysema occurring in association with multicentric reticulohistiocytosis, a papular, infiltrative cutaneous eruption that is a member of the proliferative histiocytic (CD68) spectrum of diseases.
A 48-year-old female with a 30 pack-year history of smoking and no prior cardiopulmonary disease was referred for evaluation of dyspnea. The patient had a history of an extensive, rapidly progressive, erythematous, coalescing papular eruption affecting predominantly her hands, arms, back, chest and thighs consistent with multicentric reticulohistiocytosis and confirmed by skin biopsy. Her dyspnea had been present for 2 years and had been progressive. She also reported dry coughing with no history of fever, weight loss, hemoptysis, chest pain, or night sweats. Medical therapy for her proliferative histiocytic condition included etanercept, methotrexate, and prednisone with clearance of the skin lesions at the time of her pulmonary evaluation. She did not have any family members with lung disease. There were no HIV risk factors nor history of illicit drug use. Vital signs were normal and lung auscultation revealed diminished air entry in a symmetric fashion with no wheeze. Skin findings upon initial presentation are shown in Figure 1. The remainder of the examination was unremarkable. Complete blood count and comprehensive metabolic panel were within normal range. Chest radiography revealed hyperinflation of both lungs with emphysematous changes in the upper lungs, and prominence of the central pulmonary arteries. Spirometry showed a FEV1/FVC ratio of 39, with a FEV1 of 35% of predicted. The diffusing capacity adjusted for hemoglobin was 37%. Computed tomography of the chest (Figure 2) showed extensive emphysematous changes predominantly in the upper lungs. Serum alpha-1-antitrypsin (A1AT) level was within normal limits (166 mg/dL, reference 100 - 190 mg/dL); A1AT genotyping did not detect either S or Z alleles. HIV test was negative.
The diagnosis of early-onset symptomatic emphysema is established in patients younger than 50 years. Several conditions have been associated with premature emphysema, including A1AT deficiency, HIV infection, cocaine and other inhalational drugs, primary connective tissue disorders such as cutis laxa, hypocomplemetic urticarial vasculitis syndrome, and histiocytic proliferative syndromes such as multicentric reticulohistiocytosis (1). Multicentric reticulohistiocytosis is a rare, non-Langerhans cell histiocytosis characterized by a cutaneous papulo-nodular eruption, often with destructive arthritis (2). Skin lesions can cause significant deformity, and approximately half of affected patients develop a severe disabling arthritis (2). The disease is associated with malignancy in approximately 25–30% of cases. The diagnosis is confirmed by the presence of oncocytic (“ground-glass”) histiocytes and multinucleated giant cells on histopathology of the cutaneous lesions or the synovial membrane (2).
Histiocytic proliferative syndromes such as multicentric reticulohistiocytosis must be considered in the differential diagnosis of emphysema occurring in young adult smokers.
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