1. 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.

2. 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

3. Physical Exam: Skin findings
Differential Diagnosis?

4. 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

5. What labs/imaging would you like to order?

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

7. Lab Results Hemoglobin 10.9 g/dL Platelet count 230,000/µL
WBC 11,000/µL
Hemoglobin g/dL
Platelet count 230,000/µL
Sodium meq/L
Potassium meq/L
Chloride meq/L
Bicarbonate 23 meq/L
BUN 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

8. Results: Imaging-CXR

9. What is your diagnosis?

10. 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

11. 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

12. 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.

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

14. 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.

15. 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

16. 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

17. 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

18. 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.

19. References: 1 "Blastomycosis
References: 1 "Blastomycosis." Quick Answers to Medical Diagnosis and Therapy: 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 3 Bradsher Jr., RW. Clinical manifestations and diagnosis of blastomycosis. In: UpToDate, Kauffman, C, Thorner, A, eds. UpToDate, Waltham, MA, Bradsher Jr., RW. Treatment of blastomycosis. In: UpToDate, Kauffman, C, Thorner, A, eds. UpToDate, Waltham, MA, Centers for Disease Control and Prevention. “Histopathology B. dermatitidis.” Online image. Accessed on Nov 21, MedicaLook. “Blastomycosis.” Online image. Accessed on Nov 21, 2012.