An atypical pulmonary fibrosis is associated with co-inheritance of mutations in the calcium binding protein genes S100A3 and S100A13.

BACKGROUND: Pulmonary fibrosis is one of the leading indications for lung transplantation. The disease, which is of unknown aetiology, can be progressive, resulting in distortion of the extracellular matrix (ECM), inflammation, fibrosis and eventual death. METHODS: 13 patients born to consanguineous parents from two unrelated families presenting with interstitial lung disease were clinically investigated. Nine patients developed respiratory failure and subsequently died. Molecular genetic investigations were performed on patients' whole blood or archived tissues, and cell biological investigations were performed on patient-derived fibroblasts. RESULTS: The combination of a unique pattern of early-onset lung fibrosis (at 12-15 years old) with distinctive radiological findings, including 1) traction bronchiectasis, 2) intralobular septal thickening, 3) shrinkage of the secondary pulmonary lobules mainly around the bronchovascular bundles and 4) early type 2 respiratory failure (elevated blood carbon dioxide levels), represents a novel clinical subtype of familial pulmonary fibrosis. Molecular genetic investigation of families revealed a hypomorphic variant in S100A3 and a novel truncating mutation in S100A13, both segregating with the disease in an autosomal recessive manner. Family members that were either heterozygous carriers or wild-type normal for both variants were unaffected. Analysis of patient-derived fibroblasts demonstrated significantly reduced S100A3 and S100A13 expression. Further analysis demonstrated aberrant intracellular calcium homeostasis, mitochondrial dysregulation and differential expression of ECM components. CONCLUSION: Our data demonstrate that digenic inheritance of mutations in S100A3 and S100A13 underlie the pathophysiology of pulmonary fibrosis associated with a significant reduction of both proteins, which suggests a calcium-dependent therapeutic approach for management of the disease.

D-penicillamine-induced pseudo-pseudoxanthoma elasticum and extensive elastosis perforans serpiginosa with excellent response to acitretin.

D-penicillamine (DPA)-induced pseudo-pseudoxanthoma elasticum (PXE) and elastosis perforans serpiginosa (EPS) has been reported in the past, but most of the treatment modalities used before have a sub.optimal response. We report a case of DPA-induced pseudo-PXE with extensive EPS who had an excellent rapid response to acitretin. To the best of our knowledge no such report has been published in the past, even though there is a single report of effectiveness of isotretinoin in elastosis perforans serpiginosa. SIMILAR CASES PUBLISHED: One similar case but with a different medication (reference 13).

Pseudo-Kaposi sarcoma worsening after leg vein harvest for coronary artery bypass grafting.

Acroangiodermatitis (AAD) (synonym, pseudo-Kaposi sarcoma) is a term that encompasses 2 different conditions: (1) AAD of Mali, which refers to skin lesions that mainly develop bilaterally on the lower extremities of patients with chronic venous insufficiency and is an extreme form of stasis dermatitis and (2) Stewart-Bluefarb syndrome, which consists of an arteriovenous malformation that mainly affects the limbs of young patients unilaterally. We present a case of a 68-year-old lady with progressive skin lesions on both lower limbs (right > left) as a result of chronic venous insufficiency that became worse after the leg-vein harvest for coronary artery bypass grafting was taken from the right leg. Up to our knowledge this is the first case of its kind to be reported.