2/18/19. Case 1. Question

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1 Case 1 Which of the following can present with granulomatous inflammation? A. Sarcoidosis B. Necrobiotic xanthogranulma C. Atypical mycobacterial infection D. Foreign Body Reaction E. All of the above 1

2 What is the next most appropriate diagnostic test? A. Repeat tissue culture B. Serum protein electrophoresis C. PET/CT D. Serum rheumatoid factor Necrobiotic Xanthogranuloma Rare, non-langerhans histiocytosis More than 80% present with periorbital involvement Can also occur on the trunk, extremities Extracutaneous involvement Pathology shows granuloma formation with focal areas of necrobiosis Multinucleated giant cells Cholesterol clefts Associated Disorders Most commonly associated with MGUS Hematologic disorders may precede or follow the development of NXG Clin Lymphoma Myeloma Leuk :

3 What is the most common extra cutaneous site of NXG involvement? A. Respiratory tract B. Eye C. Liver D. Spleen Necrobiotic Xanthogranuloma The respiratory tract and heart are the most common sites of extracutaneous involvement Consider bone marrow biopsy, echo and ophthalmology exam to evaluate systemic symptoms Patients without a known lymphoproliferative disorder should be monitored over time Am J Ophthalmol. 2000; 129: Int J Dermatol :

4 Case 2 What is your initial leading diagnosis? A. Neutrophilic dermatosis B. Disseminated HSV C. Cutaneous candidiasis D. Dermatophyte infection 4

5 Deep Dermatophytosis 3 distinct presentations: Majocchi s granuloma: small perifollicular papules Deep subcutaneous nodules: suppurative granulomatous folliculitis Generalized, invasive disseminated infection: large plaques with fluctuant nodules Trichophyton is commonly found in the environment and rarely causes disease in an immunocompetent host. Deep dermatophytosis been reports in highly immunosuppressed individuals. Therapy with TNF inhibitors puts individuals at an increased risk of deep fungal or atypical mycobacterial infection. CMAJ. 2017; 189:E1493 Dermatol Online J. 2011; 17:21 Mycoses. 2007; 50: J Am Acad Dermatol. 1994; 30: Which antifungal agent is excreted in sebum? A. Griseofulvin B. Ketoconazole C. Fluconazole D. Terbinafine E. Amphoterivin B 5

6 What is the mechanism of the drug-induced liver injury that has been associated with terbinafine? A. Direct toxicity B. Immune-mediated C. Idiosyncratic D. Production of a toxic metabolite Routine Laboratory Monitoring May Be Unnecessary for Terbinafine Hepatotoxicity is idiosyncratic and rare. Occurs 4-6 weeks after initiation & has features of hepatocellular necrosis and cholestatic injury Low rates (0.2%) of clinically significant lab abnormalities were detected on routine laboratory monitoring in patients taking terbinafine and griseofulvin. N = % of labs checked resulted in no clinical action Terbinafine NNT: 417 ALT, 455 ALT, 2297 Hgb Routine interval laboratory monitoring may be unnecessary in adults and children without underlying hepatic or hematologic conditions JAMA Dermatol. 2017; 153: JAMA Dermatol. 2018; 154:

7 Case 3 TNF and Granulomas TNF stimulates the production of cytokines by macrophages and T cells Increases the phagocytic capacity of macrophages Enhances the killing of intracellular pathogens via generation of reactive nitrogen species Eliminates excessive cellular responses Clin Infect Dis : S199 7

8 What is the typical exposure associated with M. marinum infection? A. Pigeon droppings B. Fish tanks C. Turtle bite D. Armadillo meat M. Marinum infection in patients on TNF Inhibitors Uncommon infection Most patients can identify water/aquarium exposure Risk appears to be highest with infliximab Atypical presentation Non-specific nodule Psoriasiform or verrucous plaque Non-specific pathology with decreased incidence of granuloma formation More aggressive disease 8

9 Which atypical mycobacterial infection will NOT cause a positive interferongamma release assay? A. M. marinum B. M. kanasasii C. M. szulgai D. M. bovis Screening for Latent TB TST can be positive in the setting of previous BCG-vaccination and infection with NTM. PPD share common antigens with NTM The interferon-gamma release assays cross reacts with NTM with the RD1 (region of difference). M. tuberculosis complex: M. tuberculosis, M. bovis, M. marinum, M. kansasii, M. szulgai PLoS One. 2014; 9: e

10 Case 4 s What is the most likely diagnosis? A. Disseminated histoplasmosis B. Lymphoma with lymphoma cutis C. Pulmonary Tuberculosis D. Syphilis E. HIV 10

11 Disseminated Histoplasmosis Most immunocompetent individuals are asymptomatic < 0.1% develop disseminated disease Can affect many organ systems: Adrenal glands: adrenal insufficiency GI: ulcers/masses causing abdominal pain, diarrhea, melena, hematochezia Bone marrow: cytopenia CNS: meningitis, encephalitis, focal lesions Heart: endocarditis, pericarditis Pulmonary: chronic cough, SOB, hemoptysis Liver/Spleen: granulomatous inflammation Skin (10-15% of patients)! Untreated disseminated histoplasmosis has a mortality rate of up to 80% Acute adrenal crisis Ann Intern Med. 1971; 4: Am J Med doi: /j.amjmed

12 Which of the following is NOT a risk factor disseminated histoplasmosis? A. AIDS B. Pregnancy C. History of solid organ transplant D. Treatment with a TNF inhibitor E. All of the above Disseminated Histoplasmosis Risk Factors: Primary immunodeficiency, AIDS Immunosuppressive medications (inc. glucocorticoids, TNF inhibitors) Solid organ transplant recipients Pregnancy A subset of middle-aged to older men have been reported with chronic progressive disseminated histoplasmosis and no risk factors.? unidentified defects in cellular immunity Medicine (Baltimore) :