In April, 2009, a 30-year old man of Turkish origin was referred to our hospital with a 5-year history of asthenia and arthralgias. 2 years earlier he had been diagnosed with rheumatoid arthritis, which did not respond to non-steroidal anti-infl ammatory drugs. On examination, he had unexplained splenomegaly (span 22 cm). Laboratory tests showed thrombocytopenia (92 × 109/L), and a normal ESR. Immunological tests including antibodies to cyclic citrullinated protein were inconclusive. Ultra sonography of the knee joints showed bilateral synovial proliferation. His knees were not red, hot, or painful, and there was no tumour. Our diff erential diagnosis included chronic infection and lymphoma. PET with labelled 18-fl uorodeoxyglucose did not reveal infl ammatory spots in joints or muscles. There was also no increased uptake in the spleen, making the diagnosis of lymphoma less likely. A bone-marrow biopsy sample showed infi ltration of foamy, vacuolated macrophages with granules positive for periodic-acidSchiff (PAS) (fi gure). The material was also highlighted by a Grocott silver stain, which raised the suspicion of histoplasmosis, and he was treated with itraconazole. However, after 4 months of treatment, there was no resolution of symptoms, and thrombocytopenia and splenomegaly persisted. A new biopsy sample of bone marrow was taken. Ultrastructural examination of the macrophages revealed cytoplasmatic lamellar lysosomal inclusions as described in lysosomal storage disorders with splenomegaly such as Gaucher disease, cholesterol ester storage disease, and Niemann-Pick disease (webappendix). Peripheral leucocyte enzyme assay showed pronounced sphingomyelinase defi ciency (1·7 nmol/mg, normal 5·1–18·7), which accords with a diagnosis of Niemann-Pick type B disease. Sequence analysis of the SMPD1 coding region revealed a homozygous mutation (p.Leu163Pro), which has not been described previously. When PAS is found in macrophages, the most common underlying diagnosis is infection (eg, Whipple’s disease, leishmaniasis, endemic mycoses). However, the patient never had abnormal infl ammatory indices. He had not travelled to a region endemic for histoplasmosis. Moreover, on Giemsa staining, the foamy macrophages had a sea-blue appearance, characteristic of Niemann-Pick disease. When last seen in February, 2011, our patient was well, without pulmonary symptoms. Niemann-Pick type B disease is a rare autosomalrecessive lysosomal storage disorder (incidence 1 in 250 000), which results from the defi ciency of acid sphingomyelinase and the accumulation of lysosomal sphingomyelin in the lysosomes of cells of the monocyte– macrophage system. The histological hallmark of the disease is the foam cell, also known as the Niemann-Pick cell, in aff ected tissues. Biochemical abnormalities include dyslipidaemia (low HDL-cholesterol) and thrombo cytopenia. The diagnosis of type B disease is usually made in childhood after splenomegaly is found. Survival well into adulthood is common; the oldest patient alive is 65 years old. In contrast to types A and C of the disease, neurological features are rare. Frequent symptoms include bleeding (49%), pulmonary infections and shortness of breath due to interstitial lung disease (42%), and joint or limb pain (39%), which was the main complaint in our patient. Growth can be delayed during adolescence, and studies with standard questionnaires report only mild impairment of quality of life. Premature coronary artery disease can occur because of the abnormal lipid profi les. There is currently no available treatment for this disease. Clinical trials with enzyme replacement therapy are planned for the near future. Close follow-up is needed because of the risk of interstitial lung disease and premature coronary artery disease. Our patient’s case illustrates that some cases of apparent infections, presenting with PAS-positive macrophages, splenomegaly, and arthralgia actually represent a type of lysosomal storage disease. Correct diagnosis allows genetic counselling and avoids unnecessary treatment