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|Year : 2009 | Volume
| Issue : 4 | Page : 367--370
Primary cutaneous aspergillosis due to Aspergillus niger in an immunocompetent patient
S Mohapatra1, I Xess1, JV Swetha1, N Tanveer2, D Asati3, M Ramam3, MK Singh2,
1 Department of Microbiology, All India Institute of Medical Sciences, New Delhi - 110 029, India
2 Department of Pathology, All India Institute of Medical Sciences, New Delhi - 110 029, India
3 Department of Dermatology, All India Institute of Medical Sciences, New Delhi - 110 029, India
Department of Microbiology, All India Institute of Medical Sciences, New Delhi - 110 029
Primary cutaneous aspergillosis is a rare entity, usually caused by A. fumigatus and A. flavus . Here, we present such a case, manifested by ulceration due to A. niger, which remained undiagnosed for a prolonged period. The immunological status was intact, although the patient had associated severe fungal infection. Recurrence of the lesion occurred despite repeated anti-fungal therapies. Anti fungal testing was done based on the broth dilution (M-38A, NCCLS, USA) method. The culture isolate was found to be sensitive to fluconazole and amphotericin B. Continuation of antifungal therapy improved the symptoms, reducing the size of the lesion.
|How to cite this article:|
Mohapatra S, Xess I, Swetha J V, Tanveer N, Asati D, Ramam M, Singh M K. Primary cutaneous aspergillosis due to Aspergillus niger in an immunocompetent patient.Indian J Med Microbiol 2009;27:367-370
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Mohapatra S, Xess I, Swetha J V, Tanveer N, Asati D, Ramam M, Singh M K. Primary cutaneous aspergillosis due to Aspergillus niger in an immunocompetent patient. Indian J Med Microbiol [serial online] 2009 [cited 2020 Jul 13 ];27:367-370
Available from: http://www.ijmm.org/text.asp?2009/27/4/367/55462
Aspergillosis is an uncommon opportunistic fungal infection caused by a variety of species of which Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger are the common ones.  It usually occurs as a complication of severe debilitating illnesses and is seen in patients suffering from malignancies, tuberculosis, silicosis and diabetes. It also occurs in patients who are receiving long-term corticosteroids, antibiotics or cytotoxic drugs and are in immunocompromised states with neutropenia. Cutaneous aspergillosis is a rare form of a locally invasive disease. It may be primary, involving the sites of skin injury following intravenous cannulation, trauma, occlusive dressing, burns or surgery. Secondary cutaneous lesions may result from widespread haematogenous seeding of the skin. In immunocompromised patients, primary cutaneous aspergillosis is most commonly caused by A. flavus and A. fumigatus . , However, this cutaneous lesion is rarely associated with Aspergillus niger . Here, we describe such an association in an immunocompetent host, and literature in this regard has been reviewed.
A 33-year-old man presented with a large non-healing painful ulcer over an erythematous plaque on the upper arm, just below the shoulder, since the last 10 years. The ulcer had gradually increased in size to 20 x 20 cm [Figure 1]. It was characterized by a punched-out margin, indurated base and erythematous granulation tissue, with purulent discharge. The ulcer developed from an asymptomatic, painless nodule of about 4 x 5 cm in size. There was no history of trauma, invasive procedure, discharging sinus or grains at that site. An empirical diagnosis of cutaneous tuberculosis was made and he received anti-tubercular treatment for two years without much benefit. He then presented to our hospital where a punch biopsy from the ulcer edge revealed necrotizing granulomatous inflammation with septate fungal hyphae showing acute angle branching, suggestive of aspergillosis. He was treated with oral ketoconazole 200 mg twice daily along with oral drops of saturated solution of potassium iodide (SSKI, 45 drops thrice daily). He took the treatment regularly for six months. This led to near complete healing of the ulcer and about 50% reduction in the size of plaque. He then took treatment, albeit irregularly, for another two months, and there was near complete resolution of the ulcer and inflammation. The patient remained asymptomatic for the next one year except for the presence of a scar. Then, slowly an ulcerated plaque formed within the scar on the arm and a new ulcer appeared in the left groin. The recurrence was treated with a combination of itraconazole and potassium iodide for six months. The ulcer responded well to therapy, but once again recurred after he discontinued treatment. The sequence of nearly 80 - 90% resolution followed by a recrudescence occurred five more times despite various combination treatments including ketaconazole, potassium iodide and itraconazole. The patient revealed that he stopped treatment on his own after some improvement because he could not afford the medication. He never took the treatment for a complete duration, as advised.
During the course of illness, he was found to have concomitant paucibacillary leprosy (pure neuritic type, which does not present with primary skin lesions) and received treatment with pauci-bacillary multi-drug therapy (PB-MDT) for six months. He developed extensive tinea corporis, which cleared after therapy with griseofulvin 250 mg once daily orally and ketoconazole 200 mg twice daily, for one year. There were no other associated medical illnesses and his general health remained good during the entire period of follow-up. The patient was found to be HIV negative with CD 4 count 965 cells/ml.
Repeated attempts to isolate the causative organisms by fungal culture during his previous hospital admissions had been unsuccessful. During the current hospital stay, a punch biopsy sample was taken from the ulcer edge as a base for histopathological and microbiological examinations. Haematoxylin and eosin staining of the tissue showed several acute angle branching septate hyphae and giant cells with dense lymphocytic infiltrate in the upper and lower dermis [Figure 2]A, B. A direct KOH mount revealed the presence of thin hyaline septate hyphae with acute angle branching [Figure 3]. The Gram stain showed the absence of bacteria and the Ziehl Neelsen stain was negative for acid fast bacilli. The biopsy material was inoculated in sabouraud dextrose agar (SDA) with and without cycloheximide in duplicate and incubated at 37°C and 25°C, respectively. After 72 hours, all tubes were seen with cottony white mycelium growth, which was soon covered with abundant black spores. No bacterial growth was detected in the culture. Microscopic characterization of the fungal isolate was carried out by preparing a lactophenol cotton blue mount from the growth. They mostly consisted of erect conidiophores. The conidiophores terminated in a vesicle covered with phialides (biseriate). The secondary phialide bore chains of globose conidia that were dark and covered the entire surface. The conidial head was large, black and radiate. The fungal isolate was confirmed to be Aspergillus niger by the above-mentioned features. We also performed antifungal susceptibility testing for fluconazole and amphotericin B using the broth dilution method (M-38A, NCCLS, USA). The isolate was sensitive to both the drugs and showed inhibition of growth for amphotericin B and fluconazole at the lowest minimum inhibitory concentration (MIC).
During the current admission, the patient was treated with ketoconazole 200 mg twice daily. After receiving the fungal culture report, intravenous amphotericin B was instituted, initially 0.5 mg / kg / day, and then increased to 0.75 mg / kg / day. However, he was unable to tolerate the drug, hence, oral ketoconazole was continued. There was significant improvement in pain and discharge, and about two-third reduction in the size of the ulcer after four weeks of treatment. The patient was advised to take treatment regularly and report for follow-up.
Aspergillus species is the most ubiquitous fungi seen in soil, water and decaying vegetations. It affects the lungs, central nervous system, naso-orbital area, skin and sometimes, it may be disseminated. Cutaneous aspergillosis is mostly caused by A. flavus, A. fumigatus, and rarely, by A. niger . Clinically, the lesion is characterized by macules, papules, plaques or haemorrhagic bullae, which may progress into necrotic ulcers that are covered with a heavy black eschar. The condition usually occurs in association with immunocompromised patients.  Our patient was not having a compromised immune status. However, cutaneous aspergillosis is not uncommon in immunocompetent patients. , Burik et al. found 6% of lesions caused by A. niger in patients not infected with HIV.  Prompt recognition and appropriate treatment is necessary to prevent adverse outcomes.
Treatment of cutaneous aspergillosis included a combination of surgical debridement and multi-drug antifungal chemotherapy.  In view of extensive tissue involvement, debridement was not done in this case, as it would have led to a larger defect. Itraconazole was used as the first line of therapy in localized lesions.  Ajith et al. reported a case of cutaneous aspergillosis which showed complete clearance of the lesion with oral itraconazole treatment.  It had to be changed to intravenous amphotericin B if the lesion worsened or if there was other evidence of clinical failure. The recurrence of the lesion in our patient was probably due to poor compliance with the antifungal agents he was administered, namely, KI, ketoconazole and itraconazole. Drug resistance was unlikely because there was a clinical response whenever he restarted regular treatment. In addition, the isolate was sensitive to fluconazole by drug susceptibility testing. To conclude, we report a case of primary cutaneous aspergillosis due to Aspergillus niger in an immunocompetent host that recurred owing to irregular treatment.
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