Disseminated Blastomycosis in a Novel Occupational Exposure

Case Report: Final Diagnosis:
 
Disseminated Blastomycosis
 
Brief history of the Present Illness: For example, “A 25-year-old male presented with...”
                  
A 29-year-old man with no significant past medical history presented to the hospital with a three-month history of wart-like lesions, non-productive cough and progressively worsening joint pain in his hands, elbows, knees, and ankles.
 
The patient moved from Eastern Canada to Southern California eight months prior to his hospital presentation. He was previously unemployed in Toronto and spent much of his leisurely time axe throwing as a hobby. However, he moved to California five months prior to his admission to begin working in an axe throwing factory; his duties included chopping wood for customers to use. He reported that his initial presenting symptom three months prior was the presence of a large papule in his left lower abdomen which eventually burst with subsequent purulent drainage. Several weeks later, he developed a wart-like lesion on his left face near his nasolabial fold, followed by other similar lesions throughout his face over the next several months.
 
Gradually, he began having a worsening non-productive cough leading to fatigue and dyspnea on exertion, and ultimately, he presented to the hospital due to swelling in his left hand and both elbows, knees and ankles. Upon examination in the hospital, he was found to have a soft, fluctuant mass in his right parietal region and a firm mass across the roof of his mouth. He denied the presence of fevers throughout his course.
 
Past Medical History including allergies (if relevant):
 
None.

Key Medications (if relevant):
 
None.
 
Epidemiological history (if relevant, such as habits, social and family history, animal exposures or travel):
 
He was originally from Canada and moved to California eight months prior, notably by air travel. He worked in an axe throwing factory, chopping wood for customers. He otherwise did not report any outdoor exposures, including no pet, livestock, insect, or tick exposure. His last international travel was to South Africa ten years prior to visit distant family members. He had a single monogamous female partner and no prior sexually transmitted infections. He denied any tobacco, alcohol, or injection drug use.
 
Physical Examination: General description, vital signs, and other relevant physical findings. For example, “The patient appeared well. The blood pressure was 120/80 mm Hg, pulse 72 beats per minute, temperature 98.6oF (37.0oC), and respirations 20 breaths per minute. The examination was otherwise normal.” Please refer to appropriate figures of physical findings if provided (Figure 1, Figure 2, etc.). Please avoid the use of abbreviations.
 
On examination, the patient appeared chronically ill; temporal wasting was present. Vital signs showed a temperature of 37.1o C and resting heart rate of 110 beats/minute. Oxygen saturation was 98% breathing ambient room air. Pulmonary examination revealed diminished breath sounds in his right apical lung and cardiac examination was notable for tachycardia with the absence of murmurs. Skin examination was significant for a 7 cm soft, fluctuant mass in his right parietal region, several 1 cm wart-like lesions across both cheeks and nasolabial folds, a firm mass on the hard palate of his oral cavity, and a draining sinus tract in left lower abdomen, near his left iliac crest. Lastly, he had a soft, fluctuant mass near his left second and third metacarpophalangeal (MCP) joints (Figure 1) and swelling in his bilateral elbows, knees, and ankles. His sites of joint swelling were without erythema or warmth, which pointed towards a perhaps more indolent infectious etiology.
 
Studies: Relevant laboratory findings (with units of measurement and normal reference ranges as these vary among institutions), radiology, etc. For example, “The hematocrit was 35.0% (reference range 41.0-53.0 in men), and the other routine laboratory test results were normal. A chest radiograph revealed a pulmonary nodule (1 cm in diameter) in the right upper lung field).” Please include pertinent positives and negatives. Refer to figures if appropriate.
 
Relevant labs included a white blood cell count (WBC) of 14.5 K/cumm L (4.5-10.9 K/cumm) consisting predominantly of neutrophils and the absence of eosinophils, platelet count of 607 K/cumm (160-360 K/cumm), normal liver function tests and elevated inflammatory markers with C-reactive protein (CRP) of 264.5 mg/L (0-7 mg/L) and erythrocyte sedimentation rate (ESR) of 75 mm/hr (No reference range).
 
Computed tomography (CT) scan of his chest, abdomen, and pelvis with contrast revealed a right upper lobe consolidative lesion abutting and eroding the ribs and an osteolytic lesion in his left iliac crest, with a sinus tract extending to the skin over his left lower abdomen. Additionally, he had a CT scan without contrast of his head which demonstrated a 7 cm mass extending from his right parietal bone with evidence of bony erosion as well.

Clinical Course Prior to Diagnosis (if relevant): Note Figures if appropriate.
 
Blood cultures and sputum cultures yielded no growth. The patient was placed on airborne isolation until three sputum samples were negative for acid fast bacilli (AFB) staining and two sputum samples were negative for mycobacterium tuberculosis polymerase chain reaction (MTB PCR) testing. Sexually transmitted infection testing, including syphilis, gonorrhea, chlamydia, and HIV testing were all negative. Antigen and antibody testing was sent for Coccidioidomycosis, Histoplasmosis, Blastomycosis, and Cryptococcus with a positive urinary Histoplasmosis antigen, negative Histoplasmosis antibody, positive Blastomycosis antibody immunodiffusion assay, and negative Blastomycosis complement fixation titer of < 1:8. A left knee aspirate was done revealing cloudy fluid, with fluid analysis suggesting the presence of inflammatory arthritis and no culture growth. Also, a lumbar puncture was performed given his parietal lesion, which showed no pleocytosis and yielded no culture growth.
 
Ultimately, a punch biopsy of his left second metacarpophalangeal joint was taken in addition to cultures from the left hip sinus tract drainage which revealed the presence and growth of Blastomyces dermatitidis, respectively. Based on the presence of the Blastomyces dermatitidis, the diagnosis of disseminated blastomycosis was established.
 
Differential Diagnosis:
 

1. Disseminated Blastomycosis


2. Disseminated Coccidioidomycosis


3. Disseminated Non-tuberculous Mycobacterium


4. Disseminated Cryptococcosis


5. Disseminated Histoplasmosis

 
Diagnostic Procedure(s) and Result(s):
 

• Left Knee Aspirate:

 

• 4,242 WBC/cumm (0-199/cumm) [87% neutrophils (< 19%)]


• Bacterial/Fungal/AFB Culture: Negative
  
  

• CSF studies:

 

• 0 WBC/cumm (0-9/cumm)


• 0 RBC/cumm (0/cumm)


• Glucose 66 mg/dL (40-70 mg/dL), Protein 28 mg/dL (15-45 mg/dL)


• Bacterial/Fungal/AFB Culture: Negative

 

• Left 2^nd MCP Biopsy (Figure 2):

 

• Fungal yeasts in multinucleated giant cells, dermal granulomatous inflammation and micro-abscess formation


• Overall histological findings and fungal species stains favor cutaneous blastomycosis.

 
Treatment/Follow-up:
 
Treatment with liposomal amphotericin was initiated for two weeks given the diagnosis of disseminated blastomycosis. Throughout his liposomal amphotericin therapy, he began experiencing improvement in his lesions and non-productive cough. Upon completion of his intravenous therapy, he was transitioned to oral itraconazole therapy. He followed up several months following the initial diagnosis in the infectious disease clinic while on oral itraconazole, with full clinical recovery and normalization of his cutaneous, mucosal, and joint findings.

Brief Discussion of Differential/Major Teaching points of case:
 
This case highlights at least four important clinical aspects. One aspect is the fact the patient presented with an indolent, disseminated disease which illustrates the full spectrum of characteristic findings seen with the disease. Blastomycosis is often manifested as a pulmonary infection, however it can disseminate to the skin, bones, and genitourinary tract (1). These manifestations include pulmonary disease with an indolent pneumonia, verrucous lesions on the face with cold abscesses in joints typical of skin disease, and painless osteomyelitis with an often-present chronic draining sinus tract to represent bone disease, all of which encompassed the patient’s presentation. However, the patient also presented with a mucosal lesion on the hard palate of his mouth which is infrequently described in the literature, as mucosal lesions are uncommon (2). In general, the incubation period for extrapulmonary symptoms is variable and can be quite prolonged, as seen in our patient who potentially contracted the infection months prior to his arrival in California (3).
 
The second more important highlight of this case is the fact that the case occurred in California. Blastomycosis is a disease seen prominently in North America, namely in the northern region of the continent (4). While this case was diagnosed in California, the disease likely was contracted in his home city in Canada. Literature shows that about eight percent of hospitalizations for Blastomyces infections occur outside of endemic regions, with California being a relatively rare region (5). A third important clinical consideration is the incubation period for the patient’s infection. It would be presumed that the patient had a prolonged incubation period of at least five months until the presentation of symptoms given his travel from Canada eight months prior to presentation and his initial symptoms appearing three months prior to presentation. Given that the literature often points to an incubation period of 3-3.5 months for Blastomyces infections, this represents a markedly longer incubation period than that has been previously described (3).
 
Lastly, the occupational exposure represents a new risk factor. This is an undescribed correlation between the occupation and the infection both in medical literature and the lay population; this presents an important and emerging occupational exposure that may lead to blastomycosis – axe throwing. Axe throwing is an activity that originated in Eastern Canada almost a decade prior, and now has expanded to both a sporting and leisurely activity on an international level. In communities throughout the United States, axe throwing is an opportunity for people to gather and partake in the sport both in the capacity of an organized league and social gathering. Certainly, an important role around the risks of axe throwing is the process of wood handling. As wood is often exported throughout different regions of the country, this profession involves both workers and consumers to be more exposed to several types of wood and the endemic fungi that are regionally linked to the wood. As this activity gains increased popularity, the risks should be acknowledged to safely handle wood and materials and should prompt providers to become aware of the risk factors of this sport to appropriately raise suspicion in the correct clinical context and screen for this activity in patients.
 
 
 
 
Final Diagnosis:
 
Disseminated Blastomycosis
 

References:
 

1. McBride JA, Gauthier GM, Klein BS. Clinical Manifestations and Treatment of Blastomycosis. Clin Chest Med. 2017;38(3):435‐449. doi:10.1016/j.ccm.2017.04.006. PMID 28797487.

 

2. Reder PA, Neel HB 3rd. Blastomycosis in otolaryngology: review of a large series. Laryngoscope. 1993;103(1 Pt 1):53-58. doi:10.1288/00005537-199301000-00010. PMID 8421419.

 

3. Klein BS, Vergeront JM, Weeks RJ, et al. Isolation of Blastomyces dermatitidis in soil associated with a large outbreak of blastomycosis in Wisconsin. N Engl J Med. 1986;314(9):529‐534. doi:10.1056/NEJM198602273140901. PMID 3945290.

 

4. Centers for Diseases Control and Prevention. (2020). Sources of Blastomycosis. Retrieved from https://www.cdc.gov/fungal/diseases/blastomycosis/causes.html

 

5. Seitz AE, Younes N, Steiner CA, Prevots DR. Incidence and trends of blastomycosis-associated hospitalizations in the United States. PLoS One. 2014;9(8):e105466. Published 2014 Aug 15. doi:10.1371/journal.pone.0105466. PMID 25126839.

 
 
IMAGES:

• Please identify as Figure 1, Figure 2 etc, and place the image(s) in the

PowerPoint presentation being submitted. Please remove patient identifiers (name, medical records number, date, etc.) from each image to protect patient confidentiality.

• Below, please note the type of image (CT scan, MRI, radiograph, physical finding photo, laboratory slide which identifies the specific stain used, etc.) and the legend/findings to accompany the individual figures.

Figure #, location of image, type of image, legend

1. Left Hand, Soft, Fluctuant Mass near 2^nd and 3^rd MCP


2. Left 2^nd MCP Biopsy Pathology Slide (H&E Stain)

Please indicate which photo or figure you think is most representative of the case.
 
Figure 2: Left 2^nd MCP Biopsy Pathology Slide (H&E Stain) – Presence of broad-based budding.