A 67-year-old man with uncontrolled diabetes was admitted with COVID-19 pneumonia. Three days later he developed black lesions on his right cheek and palate, and a swollen and paralysed right eye.1 What is the diagnosis? Critical priority group • Cryptococcus neoformans • Aspergillus fumigatus • Candida auris, Candida albicans High priority group • Nakaseomyces glabrata (Candida glabrata) • Candida tropicalis, Candida parapsilosis • Histoplasma spp. • Eumycetoma causative agents • Mucorales • Fusarium spp. Medium priority group • Scedosporium spp. • Lamentospora prolificans • Coccidioides spp. • Pichia kudriavzeveii (Candida krusei) • Cryptococcus gattii • Talaromyces marneffei • Pneumocystis jirovecii • Paracoccidioides spp. This World Health Organisation report provides information about each organism listed22 In October 2022, WHO issued a warning: ‘Fungal pathogens are a major threat to public health as they are becoming increasingly common and resistant to treatment…Most fungal pathogens lack rapid and sensitive diagnostics…During the COVID-19 pandemic, the reported incidence of invasive fungal infections increased significantly among hospitalized patients…Despite the growing concern, fungal infections receive very little attention and resources.’2 The man described above1 was in Pakistan. CT and MRI showed thickened right facial soft tissues, bilateral pansinusitis, temporal bone abnormalities, and a right cerebellar infarct. He underwent emergency right face debridement, right eye removal, and bilateral sinus surgery. Specimens showed invasion by numerous fungal hyphae (Rhizopus species) – mucormycosis.3 Intensive care included optimising glycaemia, nasogastric feeding, vancomycin, intravenous amphotericin B, and meropenem. The patient recovered. Mucormycosis is a rapidly spreading, destructive infection commonest in the Indian subcontinent and caused by mucorales fungi3 found worldwide in soil, dung, and rotting vegetation. Rhizopus can grow nearly 4cm a day.4 Mucormycosis or ‘black fungus’ affects immunocompromised people including those with diabetes, acidosis, steroid treatment, transplants, trauma or burns, haematological malignancy, dialysis, and COVID-19.5 In six months in 2021, one Indian tertiary centre treated 136 patients with acute invasive fungal rhinosinusitis; 78.7% had COVID-19, 54.4% diabetes, 64.7% steroid treatment. ‘The most common presenting feature was facial pain and swelling in 66.91%, palatal changes with dental pain in 45.58%, diminution of vision 17.64%, headache in 27.94% patients.’6 Clinical presentations of mucormycoses include: ‘sinusitis (rhino-facial, rhino-orbital or rhinocerebral), pulmonary, cutaneous, gastrointestinal, peritonitis, tracheitis, mediastinitis, renal abscess, osteomyelitis, myocarditis, endocarditis, otitis externa, keratitis, and brain abscess.’ Sinusitis is the commonest.7 Treatment includes urgent debridement of necrotic and infected tissue and antifungals, with control of blood glucose and metabolic abnormalities. A 38-year-old woman with diabetes on canagliflozin was admitted with fever and abdominal pain. A ureteric stone with urinary infection was treated by stenting and antibiotics. Ten days later she was readmitted, feverish and hypotensive. Her urine grew Klebsiella pneumoniae but blood cultures grew Candida glabrata. She recovered on micafungin and cefalozin, then fluconazole.8 Candidal infection is common in people with diabetes, especially those taking SGLT2 inhibitors.9 Candida albicans is still prevalent but widespread antifungal usage has encouraged resistant organisms such as ‘C. glabrata, C. tropicalis, C. parapsilosis, and C. krusei. It has been confirmed that 90% of fungemia cases are attributed to Candida spp., and the mortality has ranged from 40% to 80% in immunocompromised hosts. Furthermore, a high mortality rate was also detected among non-immunocompromised patients (60%) and those with diabetes (67%).’ Candida forms biofilms on medical devices like long lines, especially in diabetes.10 In critically ill adults any combination of diabetes, new onset haemodialysis, total parenteral nutrition, or broad spectrum antibiotics was associated with a rate of invasive candidiasis of 16.6% compared with 5.1% in other patients.11 Patient education is available.12 A 28-year-old man was diagnosed with type 1 diabetes after a six-month history of painful neuropathy for which he was inhaling vaporised marijuana. Then he had pneumonia; a left lower lobar infiltrate on X-ray was not followed up. After a year's fevers, night sweats, and weight loss, he was admitted with dyspnoea and chest pain due to left pneumothorax with lower lobe consolidation. The pneumothorax required surgery and lobar resection. Lung samples grew Aspergillus rugulosa…pleural fluid grew Aspergillus fumigatus.’13 Aspergillus is ubiquitous. It can cause respiratory tract hypersensitivity or lung invasion. Invasive aspergillosis (IA) can also affect other systems, such as nervous system. Aspergillosis was found in 6.9% of US intensive care patients with 80% mortality compared with a predicted 48%.14 Known risk factors include haematological malignancy, chronic lung disease, transplantation, corticosteroid treatment, neutropenia, HIV, chronic liver disease, and, probably, diabetes. In a review of 23 patients with IA without classical risk factors, nine (39%) had diabetes. Of the remaining 100 patients with IA and classical risk factors, 19% had diabetes.15 A 61-year-old woman with diabetes and hypertension was admitted with fever, vomiting, and altered mental state. She'd had a headache for three months. CSF showed a positive India ink stain and Cryptococcus was subsequently confirmed. Steroids and amphotericin B, then prolonged oral fluconazole, were eventually successful.16 Cryptococcus neoformans is found world-wide in soil and decaying wood. It can cause meningitis and fungemia, previously mainly in AIDS. A US study included cryptococcal infections in 3728 people. Non-HIV related infections were almost as frequent as HIV-related infections; the former had less typical presentations and were more likely to die. Diabetes was present in 9.1% of patients with HIV, 31.9% non-HIV non-transplant, and 61.1% of patients with solid organ transplants.17 A previously healthy 29-year-old man was found unconscious. He'd had a few days’ nausea, fatigue, polyuria, and dry lips. Diabetic ketoacidosis was diagnosed with a glucose of 91.4mmol/L (1645mg/dl). Despite treatment his condition deteriorated, he had a cardiac arrest, was resuscitated, and ventilated. Chest X-ray showed patchy opacities. He kept a parakeet so a fungal test was done revealing histoplasmosis. After three days of liposomal amphotericin B he was off the ventilator. He subsequently recovered and was ultimately thought to have type 2 diabetes.18 Histoplasmosis is found in bird and bat droppings, and in soil. It can affect any part of the body, for example the eyes. A US study of presumed ocular histoplasmosis syndrome (POHS) using logistic regression comparison between people with POHS patients and their matched controls found an increased risk for those with current or past smoking (OR 1.696 [CI 1.402–2.051]), diabetes (1.309 [1.045–1.640]), and rural location (1.516 [1.254–1.834]).19 A 45-year-old Indian man had had a painless swelling on the dorsum of his right foot for three years. His foot was not red, warm, or ulcerated. The lesion had multiple nodules and areas of soft fluctuation. New diabetes was diagnosed and treated. ‘MRI showed multiloculated cystic lesions…with intramuscular infiltration and patchy involvement of the navicular bone.’ Fungal tests were negative but a positive Mantoux test led to three months’ unsuccessful anti-TB treatment. Biopsy showed fungal hyphae. A 12x8x3cm mass was excised. Within were multiple discoloured nodules containing abscesses due to Fusarium solani. Four months of voriconazole healed the foot completely. Eumycetomas are found in Africa, Middle East, Mexico, and India, particularly in male farmers who don't wear protective footwear, and have reduced immunity. They cause swelling, and sinuses discharging grains, usually on the foot. The grains, hard fungal hyphae, are yellow-white with Fusarium solani, F. oxysporum or F. falciforme; and black with Madurella mycetomatis and M. grisea.20 Consider eumycetoma in patients in endemic areas with unusual foot lesions. WHO notes that ‘Only four classes of antifungal medicines [are] currently available, [with] few candidates in the clinical pipeline.’2 Seek local microbiological advice for diagnosis and treatment. Treatment includes resuscitation, addressing hyperglycaemia and acidosis, removal of infected medical devices, and systemic antifungals (see British National Formulary or your national guidance21). Educate patients about personal hygiene. Fungi or fungal spores are all around us in our environment, on our skin or mucosae, and inside nasal and other cavities. Most fungi don't harm us. People with diabetes are vulnerable and may have invasive or systemic fungal infections, sometimes from unfamiliar organisms. Fungal infections can be hard to recognise, hard to diagnose, and hard to treat. Liaise with your local microbiology team. In people with diabetes, puzzling clinical features, unexplained or persistent signs of infection or illness, especially in those with recent medical intervention (including antibiotics), or prolonged exposure to soil or vegetation, may indicate fungal infection. Remember fungi. They can maim and kill.
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Apr 17, 2024
Anas Askoura + 6
Open Access