Interstitial Pneumonitis, Desquamative, Familial

Description

Interstitial lung disease (ILD), or pneumonitis, is a heterogeneous group of disorders characterized pathologically by expansion of the interstitial compartment of the lung by inflammatory cells. Fibrosis occurs in many cases (Visscher and Myers, 2006).

Desquamative interstitial pneumonitis (DIP) was originally described as a pathologic entity by Liebow et al. (1965). Lung biopsy shows diffuse and uniform filling of alveoli by clusters of cells which Liebow et al. (1965) speculated to be 'desquamated pneumocytes.' Since then, these cells have been shown primarily to be pigmented alveolar macrophages. Other features include thickened alveolar septa with an infiltrate of inflammatory cells and plump, cuboidal type II pneumocytes. Mild collagen deposition without architectural distortion or honeycombing may be present. Different forms of ILD represent pathologic classifications based on histologic patterns rather than clinical diagnoses and may occur in a variety of clinical contexts (Visscher and Myers, 2006). See also usual interstitial pneumonitis (UIP; see 178500), which is associated with pulmonary fibrosis.

Although DIP occurs most often as a sporadic disorder in adults during the third to fifth decade of life and is highly associated with smoking (Carrington et al., 1978), reports of a familial form with onset in infancy and early death suggest a genetic basis (Sharief et al., 1994). Cases of DIP reported in infants are often more severe and refractory to treatment than those reported in adults (Nogee et al., 2001).

With the advent of molecular genetic analysis, some cases of familial early-onset respiratory insufficiency associated with a pathologic diagnosis of DIP have been shown to result from congenital dysfunction of surfactant metabolism (see, e.g., SMDP1, 265120) due to mutations in genes involved in surfactant metabolism (Nogee et al., 2001; Whitsett and Weaver, 2002).

Clinical Features

Tal et al. (1984) reported 3 infant sibs, 2 males and 1 female, who developed fatal respiratory failure within the first month of life. The parents were nonconsanguineous Jewish individuals of Moroccan origin. Clinical features included cough, difficulty breathing, cyanosis, failure to gain weight, and progressive hypoxia. All 3 children died before 4 months of age despite treatment with steroids and other immunosuppressive agents. Chest radiographs showed bilateral interstitial infiltrates with rapid progression to ground glass appearance. Lung biopsies showed lymphoplasmocytic infiltration in alveolar walls, fibrous thickening of alveolar walls, swelling of alveolar lining cells, and PAS-positive foamy cytoplasm in the alveolar spaces. The pathologic diagnosis was desquamative interstitial pneumonitis.

Buchino et al. (1987) described 2 families in which 2 sibs each had early infantile onset of severe respiratory distress with cyanosis and tachypnea resulting in death at ages 4 months to 3 years. Treatment with corticosteroids was not effective. Chest radiographs showed diffuse pulmonary infiltrates. Lung biopsies showed intraalveolar macrophages, prominent alveolar-lining cells, and mild interstitial fibrosis without necrosis or hyaline membrane formation consistent with DIP. All patients developed cor pulmonale. Buchino et al. (1987) suggested autosomal recessive inheritance and postulated an inborn error of metabolism.

Landing and Dixon (1979) and Landing (1987) observed a family in which 2 brothers and the brother of the mother were affected, suggesting autosomal dominant or X-linked inheritance.

Tsukahara et al. (1995) reported a brother and sister with DIP. The female died at age 1 year despite use of prednisolone and methylprednisolone, whereas the male, aged 3 years, was alive with oral azathioprine and oxygen support. The parents were unaffected, suggesting autosomal recessive inheritance.

Balasubramanyan et al. (1997) reported a male infant who presented at 8 days of age with respiratory distress and cyanosis. Lung biopsy at 8 weeks of age showed DIP. Family history revealed that 2 sibs had died in infancy and showed DIP on postmortem examination. After ineffective treatment with corticosteroids and cyclophosphamide, he was treated with chloroquine at age 14 months. He showed response within 3 weeks and was maintained successfully on this therapy for more than 9 years.