A 23-year-old woman with stage 3 chronic kidney disease from glomerulonephritis that was being treated with chronic prednisone 20 mg presented to the hospital for a kidney biopsy to evaluate worsening renal function. Her medical history included antineutrophil cytoplasmic antibody–associated vasculitis and iatrogenic Cushing syndrome. Her medications included trimethoprim-sulfamethoxazole for pneumocystis pneumonia prophylaxis. She resided in Arizona.
In the hospital, the patient incidentally noted that she had a left breast lump; at this time, she was asymptomatic. Chest radiograph was unremarkable. Left breast ultrasonography revealed a subcentimeter collection, and attempted needle aspiration did not yield any fluid.
Two days later, the patient exhibited signs of sepsis including fever, chills, tachycardia, tachypnea, and leukocytosis, as well as progressive left breast erythema, induration, and pain. Intravenous antibiotics were empirically started, and blood cultures later returned negative. With resuscitative measures, including intravenous fluids and pain management, her pain resolved and her vital signs stabilized, and she was discharged on oral linezolid. Linezolid was chosen because of concern for antimicrobial resistance given the patient’s development of a skin and soft-tissue infection while on trimethoprim-sulfamethoxazole and her immunocompromised state from chronic prednisone use.
She returned 1 week later with worsening involvement of the left breast (Figure 1) and abdominal wall, along with a low-grade fever. Repeat blood cultures continued to show no growth. Dermatology was consulted for a punch skin biopsy; the specimen site readily emitted purulent exudate (Figure 2). Gram stain of the exudate did not show any organisms.
Progressive left breast erythema and swelling despite antibiotic therapy.
Purulent exudate appeared after punch biopsy of the left breast was performed.
The patient was transferred to the intensive care unit for worsening status. She was then taken for emergent surgical debridement because of continued fevers and pain that was out of proportion to her skin findings, raising concern for necrotizing soft-tissue infection. Intraoperative findings revealed small abscesses and necrotic fat. Histopathologic study of a biopsy specimen revealed the presence of Coccidioides spherules, visualized using periodic acid-Schiff stain (Figure 3A) and Grocott-Gomori methenamine silver stain (Figure 3B), prompting initiation of intravenous fluconazole.
(A) Periodic acid-Schiff stain and (B) Grocott-Gomori methenamine silver stain of the biopsy specimen revealed Coccidioides spherules (arrows).
Over 71 days, the patient underwent debridement multiple times as part of the infection management strategy, and ultimately required skin grafting. At 3-month follow-up, her donor sites were well healed, and she did well on itraconazole after switching from fluconazole due to hair loss.
A GREAT IMITATOR
This case highlights the need for a broad differential diagnosis for invasive fungal pathogens in immunocompromised patients with soft-tissue infection, treatment failure, and endemic exposure. Differential diagnoses include mycobacterial or fungal infections, drug eruptions, graft-versus-host disease, Sweet syndrome, and posttraumatic fat necrosis. Diagnostic clues for fungal infection in this patient included chronic immunosuppression, atypical infection sites in the breast and abdominal wall, poor antibiotic response, and purulent exudate on biopsy despite earlier aspiration yielding no fluid (likely due to the time gap between the procedures). The patient’s course demonstrates that early involvement by dermatology is crucial, particularly when patients do not respond to conventional therapy.
Diagnosing disseminated coccidioidomycosis can be particularly challenging. First, although coccidioidomycosis is relatively common in endemic areas, which includes the US Southwest, where this patient was from, dissemination occurs in only about 1% of all cases and 5% of symptomatic cases, making it an infrequent clinical encounter.1,2
Also, the presentation of disseminated coccidioidomycosis often mimics that of other opportunistic infections, complicating the diagnostic process.3 Of note, patients with higher risk for dissemination include those with cell-mediated immunodeficiencies, patients of Filipino and African descent, and pregnant patients in the third trimester.2 Additionally, this case represents disseminated coccidioidomycosis with secondary soft-tissue involvement from hematogenous spread rather than primary cutaneous infection, which typically occurs through direct inoculation. This patient did not have a history or evidence of direct inoculation of the breast.
Finally, disseminated disease has a wide spectrum of cutaneous manifestations including cold abscesses (these appear without redness, swelling, or warmth),4 papules, pustules, nodules, gummas, ulcerated or verrucous plaques, and fistulae.2 The variety of skin changes possible with coccidioidomycosis supports its reputation as a great imitator.5,6
DISCLOSURES
Dr. Ackerman has disclosed consulting for Abbvie Pharmaceuticals and Timber Pharmaceuticals; teaching and speaking for Abbvie Pharmaceuticals, Amgen, ArgenyX, Bristol-Myers Squibb Co, Eli Lilly, Helsinn, Kyowa Kirin, Pfizer, Sun Pharmaceutical Industries Ltd; acting as a principal investigator at Abbvie Pharmaceuticals, Alumis, Amgen, Apollo Therapeutics, ArgenX, AstraZeneca, Biofrontera, Boehringer Ingelheim, Bristol-Myers Squibb Co., Castle Biosciences, Chemocentryx, Cor Evitas, Corrona, Inc., DermTech Inc, Eli Lilly, Exact Sciences Corporation, Glaxo Smith Kline, IgGenix, Inc., InCyte, Kymera Therapeutics, LEO Pharma, Merck, Mindera, Novartis, Regeneron, Replimune, Sanofi, Soligenix, Sun Pharmaceutial Industries Ltd., Takeda, Timber Pharmaceuticals, Trevi Therapeutics, UCB, Veradermics, and Zura Bio; and acting as an advisor or review panel participant for Abbvie Pharmaceuticals, Bristol-Myers Squibb Co, Eli Lilly, Incyte, Janssen, Novartis, Sanofi, and UCB. The other authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.
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