cc: cough, fever, dyspnea and wart-like growth on neck HPI: 35-year old otherwise healthy, nonsmoker, male presents to the clinic with complaints of intermittent cough, low-grade fever, and difficulty breathing that has persisted for the past few months. Additionally, he has noticed a nontender wart-like growth on his neck that has increased in size over this period. He reports 5 lb weight loss and has experienced some occasional joint stiffness throughout the day. He drinks 2-3 beers a week, tried marijuana 5 years ago, and denies any IV drug use or time spent in jail. He has worked as a landscaper for the past 10 years and recently moved from Missouri.

vs: temp-38.6°C (101.5°F), BP-128/82, HR-98, RR-20 Physical Exam vs: temp-38.6°C (101.5°F), BP-128/82, HR-98, RR-20 General-no acute distress HEENT-normocephalic atraumatic Neck-supple, no thyromegaly, no cervical lymphadenopathy CV-tachycardic, regular rhythm, normal S1/S2, no murmurs, rubs, or gallops Pulmonary-bilateral fine inspiratory crackles Abdomen-soft, nontender, nondistended, + BS, no hepatosplenomegaly Extremities-no cyanosis, clubbing, or edema Skin-4-5 cm raised, nontender, verrucous like lesion located on right side of neck just behind the ear

Physical Exam: Skin findings Differential Diagnosis?

Differential Diagnosis Pulmonary symptoms Blastomycosis Histoplasmosis community acquired bacterial or viral pneumonia Lung malignancy Tuberculosis Cutaneous lesion squamous cell carcinoma pyoderma gangrenosum keratoacanthoma mycosis fungoides actinomycosis

What labs/imaging would you like to order?

Labs: CBC, electrolytes ALT/AST/alkaline phosphatase/bilirubin BUN/SCr UA PPD Sputum sample and culture Lesion biopsy Imaging: CXR

Lab Results Hemoglobin 10.9 g/dL Platelet count 230,000/µL WBC 11,000/µL Hemoglobin 10.9 g/dL Platelet count 230,000/µL Sodium 140 meq/L Potassium 4.1 meq/L Chloride 95 meq/L Bicarbonate 23 meq/L BUN 18 mg/dL Creatinine 1 mg/dL ALT/AST/alk phos/bilirubin normal Urinalysis normal PPD negative Sputum broad-based budding yeast Lesion bx noncaseating granuloma Lab Results

Results: Imaging-CXR

What is your diagnosis?

Blastomycosis Is a systemic pyogranulomatous infection Acquired through inhalation of the conidia of the thermally dimorphic fungus, Blastomyces dermatitidis. Lungs are most commonly affected, though almost every organ may become involved through hematogenous dissemination May be an asymptomatic infection or develop into an acute or chronic pneumonia

Blastomycosis Epidemiology: Most cases reported in North America Endemic areas include southeastern and south-central states bordering the Mississippi and Ohio River basins as well as the Great Lakes area. Annual incidence 40/100,000 in endemic areas In endemic areas middle-aged men with outdoor occupations at greatest risk Exposure to ground soil associated with infection

Blastomycosis Etiology: Blastomyces dermatitidis There are 2 serotypes based on the presence or absence of A antigen Exhibits thermal dimorphism, mycelial phase at room temp and yeast phase at 37°C. Yeast cells are usually 8-15µm in diameter, have thick refractile cell walls, and are multinucleate Reproduce by single, large, broad-based bud.

Blastomycosis Broad-based budding yeasts Thick, double refractile cell wall 1 2 2 1

Blastomycosis Pathophysiology: Infection begins with inhalation of Blastomyces dermatitidis Conidia may be killed through phagocytosis by polymorphonuclear leukocytes, monocytes, and alveolar macrophages If conidia, the infectious stage, is not killed it may convert to the yeast phase in the tissue Yeast form is more resistant to phagocytosis and killing due to its size and thick cell wall thereby contributing to infection Primary acquired host defense against B. dermatitidis is cellular immunity mediated by antigen-specific T cells and activated macrophages.

Blastomycosis Extrapulmonary manifestations: 1. skin-second most common manifestation after pneumonia, characteristic finding is verrucous lesion, with irregular border. It may look similar to squamous cell carcinoma. Bone and joint-osteomyelitis Genitourinary system-prostatitis, epididymoorchitis, asymptomatic pyuria CNS-uncommon in immunocompetent hosts; however, those that are immunocompromised it may present as meningitis, epidural abscess, or intracranial abscess *Blastomycosis has also been reported in lymph nodes, liver, spleen, breast, adrenal gland, thyroid, eye, and oral mucosa

Blastomycosis Examples of extrapulmonary manifestations: 1 2 2 3 3 3 4 1,3. Cutaneous Blastomycosis Blastomyces osteolytic lesion CNS Blastomycosis Intramuscular Blastomycosis 5 5

Blastomycosis Treatment: Therapeutic regimen should be based on the clinical form and severity of disease, and the immune status of patient. Immunocompetent patient with mild to moderate pulmonary or non-CNS disease-treat with itraconazole for 6-12 months Immunocompromised, CNS disease, or continued disease progression with itraconazole -treat with Amphotericin B

Blastomycosis Follow-up: Monitor patient several years for relapse Prognosis: Treatment with itraconazole in immunocompetent patient results in approx 90-95% response rate Infections that relapse after initial itraconazole course typically respond well to 2nd treatment course.

References: 1 "Blastomycosis References: 1 "Blastomycosis." Quick Answers to Medical Diagnosis and Therapy: http://www.accessmedicine.com/quickam.aspx 2 Chapman S.W., Sullivan D.C. (2012). Chapter 201. Blastomycosis. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison's Principles of Internal Medicine, 18e. Retrieved November 21, 2012 from http://www.accessmedicine.com/content.aspx?aID=9110719. 3 Bradsher Jr., RW. Clinical manifestations and diagnosis of blastomycosis. In: UpToDate, Kauffman, C, Thorner, A, eds. UpToDate, Waltham, MA, 2012 4 Bradsher Jr., RW. Treatment of blastomycosis. In: UpToDate, Kauffman, C, Thorner, A, eds. UpToDate, Waltham, MA, 2012 5 Centers for Disease Control and Prevention. “Histopathology B. dermatitidis.” Online image. http://www.cdc.gov/fungal/blastomycosis/. Accessed on Nov 21, 2012. 6 MedicaLook. “Blastomycosis.” Online image. http://www.medicalook.com/Skin_diseases/Blastomycosis.html. Accessed on Nov 21, 2012.