1/ #IDFellows & #IDTwitter here is an #IDCase: 26F w/MS on Fingolimod w/chronic non-healing wound of R arm. ROS neg for fever, chills, night sweats and other signs of inflm. Exam of skin reveals 2 other macular lesions with central ulceration and crusting. Biopsy and path below:
2/ There is no headache, neck stiffness, or neuro symptoms.
Which of the following the best initial treatment? (images from Images from: Cutis. 2017 March;99(3):E16-E18)
3/ This is cutaneous cryptococcus! Cryptococcus infection of the skin can have a wide variation in presentation – from molluscum like lesions to acne-like lesions to ulcerations. It can even mimic basal cell ca. It is often diagnosed on biopsy or tissue culture.
4/ The key is understanding how to classify cryptococcal disease. Spores are inhaled and can cause localized pulmonary disease. Cryptococcus found in the skin (or any other organ) is most likely hematogenously disseminated. It is rare for direct skin inoculation.
5/ Because the definition of disseminated disease seems unclear, particularly when disease seems isolated to an organ other than lung, there have been recent attempts to change the terminology to: pulmonary, CNS, or other extrapulmonary site.
6/ Why does this matter? Because CNS and other extrapulmonary site disease should be treated the same – with amphotericin and flucytosine for induction therapy. Patients with disseminated (AKA other extrapulmonary site) likely also need LP.
7/ A recent study by @cmejiachew & @FungalDoc (PMID: 33065769) demonstrated the severity of extrapulmonary disease. Mortality rates between CNS and extrapulmonary (EP) site disease were similar (22-23%), however EP disease was less likely to receive recommended induction therapy.
8/ This study suggested incr. mortality in non-HIV, non-transplant patients (i.e. less immune supp), possibly related to delays in diagnosis, undertreatment, or more robust inflammatory responses. With mortality in > 1/5 of patients, aggressive antifungal treatment is warranted.
9/ But why did this patient get crypto to begin with? It likely is related to fingolimod, which is a sphingosine 1-phosphate receptor (S1P) modulator. This drug inhibits S1P signaling, trapping lymphocytes in peripheral lymph tissue (inhibiting T cells). PMID: 26587577
10/ Fingolimod has been associated with many opportunistic infections, including PML. However, it appears to have particular affinity for cryptococcal infection. Multiple case reports have associated Fingolimod treatment with cryptococcus infection. PMID: 28165320; PMID: 31889932
➡️ Extrapulmonary cryptococcus is disseminated until proven otherwise
➡️ Extrapulmonary dz should be tx with induction Rx (similar to CNS Dz)
➡️ Fingolimod can impair T cell immunity and is a risk factor for cryptococcus dz
12/ Thanks to @FungalDoc for much of these teaching pearls and thanks to all of you for joining in!