Pulmonary manifestations of alpha 1 antitrypsin deficiency.

Alpha 1 antitrypsin deficiency is a widely under recognized autosomal codominant condition caused by genetic mutations in the SERPINA 1 gene, which encodes for alpha 1 antitrypsin (AAT), a serine protease inhibitor. The SERPINA 1 gene contains 120 variants and mutations in the gene may decrease AAT protein levels or result in dysfunctional proteins. This deficiency leads to unopposed protease activity in tissues, thereby promoting pulmonary and hepatic disease. The most common genotype associated with pulmonary disease is the ZZ genotype, and the most frequent pulmonary manifestation is emphysema. Although its pathophysiology may differ from cigarette smoking related chronic obstructive pulmonary disease, smoking itself can hasten lung decline in alpha 1 antitrypsin deficiency (AATD). The diagnosis of AATD is made through AAT protein testing along with genotyping. AATD patients with obstructive airflow limitation may qualify for intravenous augmentation with AAT. However, there is ongoing research to allow for earlier detection and treatment. This review describes in general terms the genetic mechanisms of AATD; its pathogenesis and the impact of cigarette smoke; and its clinical manifestations, diagnosis, treatment, and prognosis. We hope to stimulate research in the field, but mostly we wish to enhance awareness to promote early diagnosis and treatment in those eligible for intervention.

The Diagnostic Dilemma of Sarcoidosis: A Case of Acute Hypercalcemia.

Hypercalcemia is a common clinical laboratory abnormality with a majority of cases attributed to malignancy or hyperparathyroidism. Although hypercalcemia is a common manifestation of sarcoidosis, it is rarely the initial presentation. Here we present a case of acute hypercalcemia in a 60-year-old gentleman, which was diagnosed as sarcoidosis following an elaborate workup, including radiological assessment and multiple organ biopsies. This case highlights the diagnostic dilemma of sarcoidosis due to varying clinical presentation that can mimic multiple conditions, including malignancy. Biopsy showing noncaseating granulomas is pathognomic of sarcoidosis. Due to its multisystemic and nonspecific presentation, selecting an appropriate biopsy site is key to diagnosis.

Sarcoidosis presenting as a solitary pulmonary mass.

Sarcoidosis has a wide varying presentation. Pulmonary sarcoidosis typically presents with bilateral hilar adenopathy and reticulonodular opacities. Very rarely it can present as a single solitary mass. Here we present a case of a 39 year old African-American male who presented with cough and pleuritic chest pain. Initial imaging revealed a right lower lobe airspace opacity, concerning for pneumonia. Despite treatment with antibiotics, symptoms and radiological findings persisted. A PET scan revealed a FDG positive right lower lobe pulmonary mass. Biopsy of the mass and lymph nodes revealed non-caseating granulomas suggestive of sarcoidosis. This case showcases a rare presentation of pulmonary nodular sarcoidosis.

A Diagnostic Dilemma of Secondary Hemophagocytosis Lymphohistiocytosis in an Elderly Patient.

Hemophagocytic lymphohistiocytosis (HLH) is a rapidly progressive fatal condition. Although well described in the pediatric population, cases of secondary HLH are seen in adolescents and young adults. In the elderly, HLH has been shown to have a poor prognosis. Owing to its varied presentation and multisystemic involvement, diagnosis is often delayed. Due to its high mortality, prompt diagnosis and treatment are crucial. Here we present a case of secondary HLH in a 69-year-old male, who presented with fever for one week. Initial laboratory workup revealed a bicytopenia and elevated creatinine. He was initially treated with broad-spectrum antibiotics; however, a comprehensive infectious workup was negative. CT scan of the abdomen revealed splenomegaly. Further investigations revealed an elevated ferritin and triglycerides. Due to the constellation of findings, he was started on corticosteroids for concerns of HLH. Bone marrow biopsy was obtained, which revealed dysplastic changes and hemophagocytosis, consistent with HLH. This case highlights the diagnostic challenge and prognosis of HLH in the elderly population, suggesting that diagnosis and treatment should not be delayed for histological confirmation.