Multiple fungal infection in a patient on chronic low dose corticotherapy.

Sir,

Cryptococcosis is a fungal infection caused by encapsulated yeast Cryptococcus neoformans and Cryptococcus gattii.[1] Aspergillus species are widely distributed in the environment such as soil and air, and the infection of human hosts occurs by inhalation of the airborne spores.[2] Here, we describe the rare case of simultaneous infection with Cryptococcus, Aspergillus, and Tinea in a patient on chronic low dose corticotherapy.

An 85-year-old Japanese farmer was referred to our department for inpatient hospital care for severe eruption and fever. He had been treated with dexamethasone 1.0 mg oral tablets for 3 months at a private dermatology clinic because of pruritis on his trunk and extremities. An initial physical examination in our department showed scaly erythema over the whole body with fever (37.7°C) and general malaise [Figure 1a and b]. Oxygen saturation decreased to 88% under room air with dyspnea. The white blood cell count (8200/μl; normal range, 3400-7300/μl), including neutrophils (6158/μl; normal range, 1214-5110/μl), serum levels of C-reactive protein (CRP) (9.78 mg/dl; normal range, 0-0.2 mg/dl), Krebs von den Lungen-6 (773 U/ml; normal range 0-499 U/ml), and beta-D-glucan (54.2 pg/ml; normal range, 0-10.9 pg/ml) were elevated. Sputum cultures and routine blood cultures were negative. Tinea infections on the body were identified by a potassium hydroxide test. Chest computed tomography (CT) showed reticular opacities and emphysema, which suggested possible pneumocystis carinii pneumonia, bacterial pneumonia, or interstitial pneumonia. A skin biopsy from scaly erythematous lesion of the abdomen was consistent with cryptococcosis [Figure 1c and d].

Figure 1

Clinical photographs (a and b) and histopathological studies (c and d). (a) Chest and abdomen. (b) Back, showing severe scaly erythema. (c) Histological findings in hematoxylin and eosin-stained sections showed histiocytic granulomas with neutrophils in dermis. Numerous round bodies were identified in the center of the granuloma (original magnification ×200). (d) Grocott staining showed black-brown fungi in the histiocytic granuloma (original magnification ×400)

Until confirmation of the diagnosis (in week 1 of hospitalization), oral administration of terbinafine hydrochloride 125 mg/day, levofloxacin 500 mg/day, trimethoprim 960 mg/day, and sulfamethoxazole 4800 mg/day, and intravenous administration of ceftriaxone sodium hydrate 1 g/day were started. On day 6, worsening of reticular opacities on CT was detected, and on day 7, serum CRP levels increased to above 15 mg/dl. On day 8, cryptococcus fungi were identified histopathologically. In addition, positive serum Aspergillus galactomannan antigen (cut-off index, 1.0; normal range, 0-0.4) was confirmed. However, serum cryptococcal antigen was negative. We diagnosed this case as cutaneous cryptococcosis accompanied with pulmonary aspergillosis. The eruption, respiratory symptoms, and the CRP level had improved with intravenous administration of amphotericin B 150 mg/day for 3 days followed by voriconazole 450 mg/day for 15 days.

Our case showed fever, worsening respiratory function, elevated levels of serum beta-D-glucan, and positive serum Aspergillus galactomannan antigen, suggesting a possibility of invasive pulmonary aspergillosis.[2] The histopathological confirmation of cryptococcus fungi and negative serum cryptococcal antigen result also suggested primary cutaneous cryptococcosis. Bird droppings serve as an excellent culture medium and may play an important part in promoting multiplication of cryptococcus fungus.[1] The patient had worked in agriculture for over 50 years, making opportunities for traumatic inoculation of cryptococcus fungus frequent. The simultaneous presence of multiple fungal infections is very rare.[34] In our case, immunosuppression caused by chronic low dose corticotherapy may have been associated with the multiple fungal infections and the case illustrates the importance of medical practitioners paying attention to chronic corticotherapy.