Case Presentation: A 59 year old woman with presumed systemic lupus erythematosus (SLE) was admitted to hospital medicine for severe pancytopenia (WBC 1.3 x109/L, hemoglobin 9.2g/dL, platelet 14×109/L). She had an extensive diagnostic work-up with rheumatology and hematology without a definitive diagnosis; rheumatology questioned her prior SLE diagnosis. Imaging showed diffuse lymphadenopathy and splenomegaly. Three bone marrow biopsies were unrevealing. Her leukopenia and thrombocytopenia remained severe, disproportionate to the anemia. Her pancytopenia was attributed to a lymphoproliferative disorder and autoimmune peripheral destruction. She was treated with high dose steroids, IVIG, MMF, and Rituximab without improvement as well as romiplostin, G-CSF, and transfusions. Splenectomy was attempted but deferred when she was found intraoperatively to have turbid ascites and adhesions. Her hospital course was also notable for episodic distributive shock without clear etiology and several infectious complications of immunosuppression. She was evaluated for macrophage activation syndrome (MAS): she had elevated soluble IL-2 receptor levels, but a bone marrow biopsy showed no hemophagocytosis. Later, she developed elevated ferritin and low fibrinogen. After several months in the hospital and cardiac arrest with resuscitation, she elected for comfort-focused care and died. Autopsy showed sarcoidosis involving the spleen, bone marrow, bilateral pulmonary hilar and subcarinal lymph nodes, and subcutaneous fat.
Discussion: Systemic sarcoidosis is characterized by noncaseating granulomatous inflammation in involved organs, typically the lungs but may affect many other organs including the reticuloendothelial system. Diagnosis often requires biopsy of affected organs and exclusion of other causes of granulomatous inflammation. Splenomegaly in sarcoidosis can lead to pancytopenia.Hospitalists commonly care for patients with diagnostic dilemmas. A prolonged hospitalization generates thousands of points of potential diagnostic data and can cause information overload. Moreover, laboratory results that slowly evolve over time can be difficult to appreciate during a long hospitalization. These diagnostic challenges are compounded by frequent provider turnover and multiple specialty involvement. In this case, the diagnosis of systemic sarcoidosis and its complication of MAS were missed. Despite the patient’s splenomegaly and lymphadenopathy, sarcoidosis was not considered, perhaps because of multiple other tests and findings competing for attention as well as SLE diagnostic momentum. In retrospect, the patient met criteria for MAS given cytopenias, splenomegaly, elevated soluble IL-2 receptor levels, elevated ferritin, and low fibrinogen, though these abnormalities were detected asynchronously. Unfortunately, this patient had three falsely negative bone marrow biopsies, which undoubtedly influenced clinical reasoning. Splenic or lymph node biopsy may have allowed for a premortem diagnosis of sarcoidosis.
Conclusions: The diagnosis of rare manifestations (severe cytopenia and MAS) of a rare disease (systemic sarcoidosis) is challenging. Prolonged hospitalization increases the potential for diagnostic error through information overload, challenges in recognizing slowly evolving lab abnormalities, and frequent provider turnover. Hospitalists should be mindful of diagnostic anchoring and inertia when caring for patients during prolonged hospitalization.
