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.
