FUO: sarcoidosis? Whipples?

Intestinal histology with PAS + foamy macrophages found in Whipple's disease

Intestinal histology with PAS + foamy macrophages found in Whipple's disease

Today, we discussed a case of a patient with 4 weeks of fevers without identified cause associated with 40 pound unintentional weight loss then one week of diarrhea, tremors, myoclonic jerking, and findings of lymphocytic pleocytosis on LP and RUL nodule and hilar and mediastinal lymphadenopathy on CT chest. Ultimately, following bronchoscopy, diagnosis of sarcoidosis and possibly neurosarcoidosis was made. A question of Whipple's disease was also raised. Some learning points:

1) There is no definitive diagnostic test for sarcoidosis. Instead, the diagnosis of sarcoidosis requires compatible clinical and radiographic manifestations, exclusion of other diseases that may present similarly, and histopathologic detection of noncaseating granulomas.

  • ACE levels have a NPV of 60% (not a good rule out test) but a PPV of 90%.
  • CD4/CD8 ratios of >4:1 have a 93% PPV and if <1:1 has NPV of 100%

2) Neurosarcoidosis is rare, only 5-10% of patients, but can affect any portion of the central or peripheral nervous system. Common syndromes include myopathy, peripheral neuropathy, hydrocephalus, aseptic meningitis, cranial mononeuropathy, neuroendocrine dysfunction, a focal or multifocal encephalopathy, or myelopathy.

3) What about Whipples? As Dr. Obley pointed out today Whipples can mimic sarcoidosis. Whipples often starts with mild GI complaints, but presentation can be variable given the multiple systems that can be involved, and patients can go years without seeking medical attention.

Less than 10-15% of patients with Whipple disease eventually develop clinically significant CNS involvement, with a small group actually presenting with CNS involvement which can include: AMS, cognitive changes, movement disorders (eg, myoclonus), hypothalamus-related problems (eg, polydipsia, hyperphagia, decreased libido), seizures, pupillary abnormalities, and psychiatric disease. Hmmm...