Today we presented a case of a 44 year old M with no significant past medical history who reported a 3 month history of shortness of breath and abdominal pain and distension. Given the history and physical exam findings consistent with a volume overloaded state, the initial differential diagnosis included causes of heart failure, liver disease and renal disease (ESRD, nephrotic syndrome). Labs were significant for an infiltrative pattern of liver injury (significantly elevated alkaline phosphatase, minimally elevated transaminases and normal bilirubin) as well as an elevated globulin gap of 4.8. TTE showed reduced an ejection fraction of 35% and abdominal ultrasound demonstrated cirrhosis and ascites.
Work-up of an elevated globulin gap:
– An elevated globulin gap (difference between the total serum protein and serum albumin concentration) should always be evaluated. The first step in evaluation is to determine whether it represents a monoclonal or polyclonal gammopathy.
– Causes of polyclonal gammopathy include viral infections (acute HIV, hepatitis C), connective tissue disorders and other causes of persistent inflammation (acute phase reactants will cause an increase in the globulin gap).
– Causes of monoclonal gammopathy include MGUS, multiple myeloma, Waldenstrom’s macroglobulinemia, amyloidosis and lymphoma.
– An SPEP (shown below), immunofixation and free light chain assay should be ordered to help determine the etiology of the protein gap. Remember that SPEP is the initial screening test and the sensitivities of serum immunofixation and free light chain assay are higher for detecting the presence of paraproteins. An abnormal free light chain ratio indicates overproduction of either kappa or lambda light chain.
Today in Goldstein Morning Report we presented a case of a 45 year old M with no PMH who was brought in for acute encephalopathy and witnessed seizures. On exam the patient was found to have multiple cranial neuropathies and labs were significant for a positive RPR (1:32). The patient had a lumbar puncture performed which showed 4 WBCs (lymphocytes), glucose 67 and protein 54 and CSF VDRL was found to be reactive.
– Clinical signs of neurosyphilis include meningitis, stroke, acute/chronic encephalopathy, loss of vibration sense, cranial nerve dysfunction and auditory/ophthalmic abnormalities.
– The diagnosis of neurosyphilis is based on clinical suspicion, serologic tests and CSF analysis.
– Remember that CSF abnormalities can occur in early syphilis, and may not be clinically significant in the absence of neurologic signs/symptoms.
– In early neurosyphilis, serum nontreponemal (VDRL, RPR) and treponemal tests (FTA-ABS) are generally reactive, however in late neurosyphilis VDRL and RPR may be nonreactive and FTA-ABS should always be performed.
– CSF-VDRL is highly specific and a reactive test is diagnostic for neurosyphilis, however the sensitivity is much lower.
Diagnosis of neurosyphilis in an HIV- patient
– In patients with a nonreactive CSF-VDRL, treatment depends on further CSF findings.
—> If the CSF WBC>5, treat for neurosyphilis.
—> If the CSF WBC<5 but the CSF protein >45, treat for neurosyphilis.
Diagnosis of neurosyphilis in an HIV+ patient
– Similarly to HIV- patients, further CSF studies must be used to diagnosed neurosyphilis when the CSF-VDRL is negative. However HIV can cause a mild CSF pleocytosis and protein level (especially in those with CD4>200, detectable HIV RNA and not on ART).
–> If the CSF WBC >20, treat for neurosyphilis.
–> If the CSF WBC is 6-20, treat for neurosyphilis if the CD4<200, HIV RNA<50 and on ART
–> If the CSF WBC is ≤5, do not treat.
Today we presented a case of a 35 year old female with no past medical history presenting with 3 weeks of fevers, rash, sore throat, weight loss and diffuse joint pain. The differential for this presentation is broad, including infection, malignancy and rheumatologic disorders. Labs were significant for very mildly elevated transaminases, mild hyponatremia and normal white count with elevated neutrophils.
– Given the constellation of symptoms, multiple infectious causes were considered including murine typhus, acute HIV, and parvovirus (the rash associated with parvovirus can intensify with warm water and showers). The patient reported eating queso fresco so Brucellosis and Q fever were also possible (chronic Q fever can present with high fevers and mild transaminitis).
– Malignancy was considered, in particular hematologic malignancy given the presence of B symptoms. However the presence of joint pain and evidence of synovitis made hematologic malignancies less likely. Rheumatologic diseases such as RA and SLE can also present with similar symptoms.
The patient was ultimately diagnosed with Adult Onset Still’s Disease after infection and other rheumatologic diseases were ruled out, and iron panel showed a ferritin of >8000. Still’s disease is a diagnosis of exclusion made upon characteristic clinical and laboratory features.
– Our patient satisfied 3/4 of the major Yamaguchi criteria (patient did not have leukocytosis >10,000 however did have a PMN predominance) and 3 minor criteria (listed below).
Thanks to PGY3 Alex Yang for doing a great presentation!