A rare case of atypical bone marrow sarcoidosis without pulmonary involvement in a Japanese woman

Background

Sarcoidosis is a multisystemic disease characterised by defective cell-mediated immunity with formation of non-caseating granulomas in various organ systems. The lungs and mediastinal lymph nodes are most commonly affected, as seen in more than 90% of sarcoidosis cases. Moreover, less than 0.5% of sarcoidosis cases with bone marrow involvement also have pulmonary involvement. Therefore, bone marrow sarcoidosis without pulmonary involvement is very rare. Here, we report a case of bone marrow and hepatic sarcoidosis without pulmonary involvement in a Japanese woman whose symptoms were fever, night sweats and weight loss.

Case presentation

Having only hypertension and hyperlipidaemia in the medical history, a 69-year-old woman presented with fever of unknown origin, night sweats and weight loss, which had persisted for 2 months. She experienced weight loss of 5 kg over this period. Her medical history was notable for hypertension and hyperlipidaemia.

On admission, her temperature was 38.5°C and heart rate was 101 bpm. On clinical examination, there was no disturbance of consciousness, tendon reflexes were normal and no pathological reflexes were noted.

She had no rashes, subcutaneous nodules or postinflammatory skin changes. No psoriatic nail changes were seen. The salivary glands were not enlarged, and there was no palpable systemic lymphadenopathy.

Investigations

On admission, aspartate aminotransferase was 44 U/L, alanine transaminase was 36 U/L, alkaline phosphatase was 1613 U/L, hepatic enzymes were partialy elevated and function was normal. Serum calcium level was 10.3 mg/dL. C reactive protein level was increased (6.02 mg/dL; reference: <0.3 mg/dL), as was erythrocyte sedimentation rate (64 mm/hour). There was an increase in soluble interleukin-2 receptor (IL-2R): 4030 U/mL; no increase of ACE level: 15.8 U/L. Antinuclear antibody titre was less than 1:40. Both myeloperoxidase–antineutrophil cytoplasmic antibody and proteinase-3 antineutrophil cytoplasmic antibody titres were less than 1:40, and interferon-gamma release assay was negative. Blood culture was also negative. Immunoglobulin G (IgG) was slightly elevated (1858 mg/dL), but IgG4 was normal (31.0 mg/dL). There were no specific electrocardiographic findings and echocardiogram findings. CT scan of the chest did not show any evidence of pneumonia or perimediastinal or hilar lymphadenopathy. ¹⁸F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scans showed uptake in multiple hypermetabolic osseus lesions in both shoulders, the wrist, the whole pelvis and multiple vertebral bodies (figure 1). In addition, there was increased uptake in the spleen and liver. Therefore, we performed liver biopsy and bone marrow biopsy at right posterior superior iliac crest, which revealed non-caseating epithelioid granulomas (figures 2 and 3). No findings suggestive of vasculitis, malignancy and lymphoma were noted. Transbronchial lung biopsy revealed no findings of granulomatous tissue and the CD4/CD8 ratio was 1.63 in bronchoalveolar lavage fluid taken from the middle lobe. Within the scope of our investigations, no findings suggested infectious disease. Opthalmologic findings were normal. These clinical features were compatible with a diagnosis of sarcoidosis.

Figure 1

FDG-PET images. FDG-PET scan shows diffusely increased focal FDG uptake localised to multiple bone lesions, including the whole pelvis and to multiple lesions in the liver, the spleen and some joints. We performed bone marrow biopsy at right posterior superior iliac crest. FDG-PET, ¹⁸F-fluorodeoxyglucose-positron emission tomography.

Figure 2

Liver biopsy. This section shows an epithelioid cell granuloma, which is a compact formation of molecular phagocytes in the lobular and periportal distributions. There is no evidence of malignancy or primary biliary cirrhosis. H&E stain, ×300.

Figure 3

Bone marrow biopsy. This section shows epithelioid cell granulomas, some of which include Langerhans giant cells. There is no evidence of lymphoma or a massive increase in blastoid cells. H&E stain, ×300.

We obtained granulomatous tissues where FDG-PET showed areas of inflammation, showing consistency between the clinical and radiographic manifestations. In addition, we excluded diseases that may present similarly to sarcoidosis, including malignant lymphoma, infectious diseases and autoimmune diseases. Histopathological examination revealed non-caseating granulomas. Therefore, we diagnosed her illness as sarcoidosis.

Differential diagnosis

Based on the clinical symptoms, the increase in IL-2R and the FDG-PET findings, malignant lymphoma was the most important differential diagnosis. However, the liver and bone marrow biopsy findings did not show atypical lymphocytes. In the differential diagnosis of granulomas found in pathological examinations, infectious and autoimmune diseases should be focused on. In particular, tuberculosis, endemic fungal diseases, viral hepatitis, toxoplasmosis, cat scratch disease and syphilis should be considered as infectious diseases. However, the results of serological tests and contact history were not compatible with these possible diagnoses. Autoimmune disorders that can cause liver and bone marrow granulomatous inflammation include Langerhans cell histocytosis, IgG4-related disease. Our patient had no evidence of Langerhans cell histocytosis on biopsy and no characteristic findings of IgG4-related disease.

Treatment

Prednisolone was administered for 3 days at an initial dose of 30 mg/day (0.5 mg/kg/day). Her symptoms, including fever and general malaise, gradually improved. Thereafter, the dose was tapered by 5 mg/week while checking that the symptoms did not worsen. After the dose reached 15 mg/day, the tapering interval was reduced to 2.5 mg/week.

Outcome and follow-up

She was discharged on day 58 and was followed up on an outpatient basis at our hospital. She became diabetic and began taking hypoglycaemic medication. She is now taking prednisolone 5 mg/day as an outpatient and her progress has been good as of this writing.