Case Presentation: 41 y/o male with DM1, ESRD on HD, calciphylaxis and anemia presented with worsening pain, malodor and bleeding of his left thigh. He was recently diagnosed with calciphylaxis in this region. Exam revealed a large unroofed blister with surrounding dark-colored skin (Figure 1). CT of the left thigh showed gas in the anterior and medial thigh soft tissues with concern for necrotizing fasciitis (Figure 2). The patient required multiple deep wound debridements with wound vacuum dressing. Broad spectrum antibiotics were added. Initial cultures showed Staph epidermidis and Clostridium perfringens. Fungal and mycobacterial cultures were negative.Several weeks into hospital stay, histopathology of an adjacent enlarging leg lesion plus earlier negative fungal wound cultures revealed Rhizopus infection. The patient was diagnosed with necrotizing fasciitis from cutaneous mucormycosis at a calciphylaxis site. Liposomal amphotericin B was initiated with posaconazole later added. The patient later developed right eye swelling. CT head/neck was done without eye pathology seen but did show a left upper lung lobe cavitary lesion. This was confirmed by chest CT. Bronchoscopy with bronchoalveolar lavage was performed. Serum fungal studies and tissue cultures were negative. The patient eventually developed a worsening right pleural effusion, diagnosed as Enterobacter empyema. Despite aggressive therapy, his overall status declined. He was transitioned to comfort care and passed away. A cutaneous mucor infection with progression to systemic disease was suspected.
Discussion: Mucormycosis (MCR) is a rare fungal infection caused by members of the order Mucorales with the most common genus members including Rhizopus, Mucor, Lichtheimia and Rhizomucor (1-3). Mucorales species are difficult to grow, but thrive in high glucose, acidic, and iron-rich conditions (4). Risk factors include DM, hematologic malignancies, hx of transplant, trauma, iron overload, steroid use, COVID-19 infection (5), malnutrition and injection drug use (1,2,5). In this case it was felt that DM plus skin injury from a calciphylaxis wound were the main risk factors. There have been very few cases of MCR reported in the setting of calciphylaxis (6,7). Infection occurs when spores are inoculated into areas of trauma or inhaled into respiratory passages. Cutaneous MCR can remain localized or progress to systemic disease as was felt to occur with this patient (5,8,9). Diagnosis is through culture and histopathology, but cultures are often negative (10). Immunohistochemistry and molecular assays are limited with variable sensitivity and specificity (11). Treatment is multimodal: consisting of surgical debridement and medical intervention with liposomal amphotericin B followed by delayed-release posaconazole (2). Management of hyperglycemia, metabolic acidosis, neutropenia, and iron overload is crucial. There is wide variability in the degree of mortality from 40-80% (2). Secondary infections, such as the Enterobacter seen in this case, can further complicate the clinical picture.
Conclusions: MCR is a rare disease with a high mortality rate. In addition to having DM, the patient had an open wound from calciphylaxis which was felt to place the patient at additional risk for infection. Diagnosis is often challenging and requires a high index of suspicion and prompt action. This case underscores the need for vigilant and aggressive management.
