JULY 11, 2017

CASE 1: CRYPTOCOCCAL MENINGITIS

A 54/F with ESRD s/p deceased donor kidney transplantation in 2012, p/w 3-months of headache and progressive decline in mental status; CSF showed lymphocytic pleocytosis and low glucose with an opening pressure of 23 cm H₂O; brain MRI was normal; BioFire FilmArray PCR testing for bacteria, yeast, and viruses (performed at another institution) only notable for a positive HHV-6; on transfer to our hospital, serum and CSF cryptococcal antigen were both positive (1:10 and 1:20, respectively); treated with liposomal amphotericin with good clinical response.

1. Symptoms of meningitis (i.e. headache ± fever) that persist for > 4 weeks and run an indolent course suggest chronic meningitis. The differential diagnoses shift away from common bacterial and viral pathogens that cause acute meningitis. Some of the important etiologies of chronic meningitis are:

• Fungal: Cryptococcus, endemic fungi particularly Coccidioides and Histoplasma

• Bacteria: Mycobacterium tuberculosis, syphilis, Lyme disease

•  Non-infectious: lymphomatous meningitis, sarcoidosis, Behcet’s syndrome

2. The discussion of the case centers on the uncertainty in diagnosing cryptococcal meningitis using tests other than direct microscopic examination, culture (gold standard), histopathology, and serum/CSF antigen detection. This patient had a negative BioFire FilmArray PCR testing at another institution (likely a false negative test) but positive serum and CSF cryptococcal antigen test in our hospital. This resulted in a missed opportunity to diagnose and treat cryptococcal meningitis early. Below is a summary of important points that you should know about this test.

• It is a qualitative PCR that tests for 14 microorganisms (6 bacteria, 7 viruses, and 1 yeast: Cryptococcus neoformans/gattii).

• Compared to cryptococcal antigen testing, it has a sensitivity of only 12.5% (from the FDA licensing data: 7 specimens were positive by cryptococcal antigen testing but were negative by FilmArray; all 7 specimens were collected after patients received antifungal therapy).

• False negative FilmArray results usually come from specimens with low cryptococcal antigen titers.

• The bottom line is that given the low sensitivity of this test for diagnosing cryptococcal meningitis, the results should be interpreted with caution. 

CASE 2: RAT BITE FEVER

An 8 year old girl p/w 5 days of vomiting, diarrhea, fever, joint pains and rash; exam showed scleral icterus, significant bilateral MCP and PIP joint swelling and tenderness, petechial and macular lesions on the distal extremities; at home, has dogs, cats, ferrets, rabbits, hamsters, and recently purchased pet rats; diagnosed with rat bite fever

1. Five things you should remember about rat bite fever (RBF):

• RBF is caused by Streptobacillus moniliformis in the US and Spirillum minus in Asian countries. Both are gram negative bacilli.

• Suspect in patients (i.e. lab personnel, children) with any rat exposure (bites > scratches > others: even handling of rats). Bites/scratches from animals that prey on rats (e.g. dogs, cats, ferrets) can also transmit the disease.

• Cardinal symptoms that should raise suspicion for RBF: fever + distal extremity petechial rash (can be in the palms and soles) + migratory arthralgia/arthritis (knees > ankles, elbows, wrists, hip).

• Diagnosis is difficult as the bacteria require enriched media to grow. Hence, empiric diagnosis and treatment for RBF are oftentimes done. Culture (blood > synovial fluid) confirms the diagnosis. Examination of the specimen to look for the characteristic bacteria can also be done.

• PCN is the treatment of choice (alternative drug: doxycycline) given IV x 1 week then switched to oral antibiotic for another week. The Jarisch-Herxheimer reaction can sometimes occur after antibiotic treatment is started.

2. Since empiric diagnosis and treatment for RBF are sometimes done, keep these differential diagnoses always in mind to guide diagnostics and treatment:

• Leptospirosis: differs from RBF in that joint pain/swelling is not a prominent symptom

• RMSF: striking similarity with RBF in the presence of petechial/purpuric rash in the distal extremity/palms/soles; joint pain/swelling is not a prominent symptom

• Disseminated gonococcal infection (DGI): striking similarity with RBF in the presence of migratory arthritis; the rash in DGI is very different (pustular > vesicular, very few in number, usually 2-10 in total) 

CASE 3: POSTOPERATIVE PYODERMA GANGRENOSUM

A 54/M with a prolonged hospital stay after a CABG procedure because of non-healing of his surgical wounds (thoracotomy, chest tube, vein harvest sites) associated with purulent drainage and non-response to broad-spectrum antibiotics and multiple debridement; all cultures were unrevealing; diagnosed with postoperative pyoderma gangrenosusm; treated with steroids with good response

1. Suspect postoperative pyoderma gangrenosum (PPG) in a patient with non-healing or worsening surgical wounds after debridement (pathergy), nonresponse to broad spectrum antibiotics, and with negative bacterial/fungal cultures. Consult Dermatology if PPG is suspected.  

2. PPG is a non-infectious, chronic neutrophilic dermatosis that is pathologically similar to pyoderma gangrenosum associated with systemic diseases (e.g. inflammatory bowel disease, rheumatoid arthritis). In a review of literature, most patients diagnosed with PPG, however, lack any systemic autoimmune diseases.

3. Other causes of pathergy: Behcet’s disease, Sweet’s syndrome.