|Year : 2018 | Volume
| Issue : 1 | Page : 136-139
A first-line antiretroviral therapy-resistant HIV patient with rhinoentomophthoromycosis
Rachita Dhurat1, Rajendra J Kothavade2, Anand Kumar2
1 Department of Dermatology, Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, Maharashtra, India
2 Department of Medical Microbiology, Sepsis Research Group, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
|Date of Web Publication||2-May-2018|
Dr. Rajendra J Kothavade
Department of Medical Microbiology, Sepsis Research Group, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba
Source of Support: None, Conflict of Interest: None
The Conidiobolus coronatus-related rhinoentomophthoromycosis in immunocompetent and immunocompromised (HIV negative) individuals has been treated successfully with antifungal drugs. However, C. coronatus infections in first-line antiretroviral therapy (ART)-resistant (HIV infected) individuals particularly with rhinoentomophthoromycosis have not been reported previously. Here, we describe a case of itraconazole non-responding rhinoentomophthoromycosis in an HIV-infected patient with first-line antiretroviral (ART) drug resistance which was successfully managed through systematic diagnostic and therapeutic approaches in dermatologic setting. A 32-year-old HIV-1-infected man presented with painless swelling, nasal redness and respiratory difficulty. The patient was receiving first-line ART and had a history of traumatic injury before the onset of nasopharyngeal manifestations. The patient's previous history included oral candidiasis and pulmonary tuberculosis.
Keywords: AIDS, antiviral drugs, Conidiobolus coronatus, HIV, rhinoentomophthoromycosis
|How to cite this article:|
Dhurat R, Kothavade RJ, Kumar A. A first-line antiretroviral therapy-resistant HIV patient with rhinoentomophthoromycosis. Indian J Med Microbiol 2018;36:136-9
|How to cite this URL:|
Dhurat R, Kothavade RJ, Kumar A. A first-line antiretroviral therapy-resistant HIV patient with rhinoentomophthoromycosis. Indian J Med Microbiol [serial online] 2018 [cited 2018 Sep 21];36:136-9. Available from: http://www.ijmm.org/text.asp?2018/36/1/136/231656
| ~ Introduction|| |
Conidiobolus coronatus is a recognised human pathogen that causes subcutaneous fungal infections, often on the face of immunocompetent patients from tropical and subtropical regions, including India.,, However, C. coronatus infections in first-line antiretroviral therapy (ART)-resistant HIV-infected individuals, particularly those with rhinoentomophthoromycosis, have not been previously reported. Most cases of C. coronatus- related rhinoentomophthoromycosis in immunocompetent and immunocompromised HIV-negative patients have been successfully treated with antifungal drugs such as ketoconazole, fluconazole and itraconazole., Immunocompromised hosts, particularly those with HIV infection or AIDS, are vulnerable to variety of fungal infections and experience poor therapeutic responses.,,,, Resistance to first-line ART is an emerging issue, particularly in cases of treatment noncompliance.,, This report describes a case of itraconazole-nonresponsive rhinoentomophthoromycosis in an HIV-infected patient with first-line ART drug resistance and the unique therapeutic approach utilised to successfully manage the case.
| ~ Case Report|| |
A 32-year-old HIV-1-infected man presented with painless left nasal mucosal swelling and erythema causing respiratory difficulty. He stated that these signs and symptoms were present for approximately 9 months. On investigation, it was determined that the probable underlying cause of the infection was a traumatic injury to the nose by rotten wood the onset of his symptoms. He was afebrile and had no signs of oral candidiasis, regional lymphadenopathy, diarrhea or any other signs of gastrointestinal infections. He had no history of headaches or meningitis, and no other symptoms were elicited during the investigation.
Examination of the specific focal lesion revealed an ill-defined erythematous mass with a crust present unilaterally over the left side of the nose [Figure 1]a and extending up to the bridge of the nose [Figure 1]b. Systemic and neurologic examination did not reveal significant findings, and the patient was haemodynamically stable. The patient's vision was normal, and no other complications beyond the affected area were noted. A computed tomography scan of the paranasal sinuses confirmed middle and inferior turbinate hypertrophy with adhesions, leading to blockage of the nasal pathway [Figure 2]a and [Figure 2]b. A 4-mm skin biopsy was taken from the nasal mucosal mass with the utmost precaution. Histological examination of the biopsied specimen stained with Hematoxylin & Eosin stain revealed acanthosis with dense neutrophilic, lymphocytic and eosinophilic infiltration throughout the dermis [Figure 3]a. Fine needle aspiration cytology of the inferior turbinate mass revealed a granulomatous infiltrate containing large numbers of lymphocytes, macrophages, giant cells and epithelioid cells [Figure 3]b. No fungal elements were observed in periodic acid–Schiff-stained tissue sections.
|Figure 1: (a) Erythematous, mildly tender subcutaneous swelling on the left side of the nose. (b) Rhinoscopy: A pale-white mass obstructing the nasal passage|
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|Figure 2: (a and b) Computed tomography scan of paranasal sinuses: middle and inferior turbinate hypertrophy with adhesions causing obstruction of nasal passage|
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|Figure 3: (a and b) Epidermis: mild-to-moderate acanthosis. Dermis: dense infiltration of neutrophils, lymphocytes and eosinophils|
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Further, the processed specimen was inoculated and incubated at both room temperature and at 37°C, on Sabouraud's dextrose agar (SDA) medium.
Fungal growth with small satellite colonies at the periphery was only visible on SDA medium (at 25°C) within 4 days [Figure 4]. Repeat biopsy specimens and a minimum of three sets of processed cultured specimens demonstrated consistent fungal growth on SDA. The mature obverse side of the colonies were tan to brown in colour within 4 days due to aging, and the reverse side was white in colour. A lactophenol wet mount of the fungus on the SDA plate revealed unbranched sporangiophore-bearing sporangiole at the tip and typical pyriform conidia with prominent papillae. A comparison with the macroscopic and microscopic features of a standard strain of C. coronatus (ATCC PTA-4132) confirmed the isolated fungus to be C. coronatus. Confirmation of C. coronatus using uncommon molecular tests such as direct DNA sequencing of internal transcribed spacer and D1/D2 regions of rDNA and serum levels for drug concentration was out of question because of limited health insurance and patient's personal financial condition.
|Figure 4: Conidiobolus coronatus growth on Sabouraud's dextrose agar at 25°C|
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Based on the clinical presentation and mycological results, the patient was started on oral itraconazole at a twice-daily dose of 200 mg and a saturated potassium iodide solution at an initial dose of 5 drops thrice daily, gradually increasing to a maximum of 40 drops per day. Despite proper adherence to first-line ART(Zidovudine (AZT) + Lamivudine (3TC) + Nevirapine (NVP)) and itraconazole, the patient exhibited worsening of respiratory difficulty due to increased nasal mucosal swelling and obstruction. In addition, the development of weakness, dyspnea on exertion and losses of appetite and weight suggested first-line ART failure. The viral load and CD4+ count test results confirmed this suspicion. Based on the findings, significantly lowered CD4+ count (50 cells/mm 3), an increased HIV-1 RNA viral load of 50,000 copies/ml, clinical symptoms and failure to respond to itraconazole, the patient was immediately switched to second-line ART due to his critical condition. The patient was started on ART that included 300 mg of tenofovir, 300 mg of lamivudine, 300 mg of atazanavir and 100 mg of ritonavir once daily along with the continuation of oral itraconazole at 200 mg/day and saturated potassium iodide drops.
Within 3 months of treatment patients respiratory difficulties resolved and the nasal mucosal swelling significantly decreased. The most recent follow-up of the patient showed significant improvement in the CD4+ count (from 50 cells/mm 3 to 380 cells/mm 3) with significant resolution of the nasal mucosal swelling and resolution of respiratory difficulties.
| ~ Discussion|| |
Before the advent of highly active ART (HAART) in 1996, infection management in AIDS patients was a major challenge, with consequent increases in mortality rates. With HAART therapy or newly improved antiretroviral drugs, it has been possible to control HIV viral replication with the beneficial effect of increasing the numbers of CD4+ T cells, which assist antifungal drugs in the clearance of chronic fungal infections.,,, This particular case highlights the occurrence of C. coronatus-related rhinoentomophthoromycosis in an AIDS patient who initially exhibited therapeutic failure due to an apparent underlying resistance to ART. The histopathological patterns of such infections vary in AIDS patients as a result of severe T cell population depletion with deficiency. Overall, the therapeutic response to or clearance of fungal infections is more rapid in immunocompetent individuals than in immunocompromised patients. For example, cutaneous infections in immunocompetent patients induce granulomatousreactions against fewer numbers of encapsulated yeasts, whereas AIDS patients normally exhibit heavy colonisation of encapsulated yeasts, as seen in gelatinous stroma. Overall, the therapeutic response to or clearance of fungal infections is more rapid in immunocompetent individuals than in immunocompromised patients.
In cases of C. coronatus infections in immunocompetent and immunocompromised individuals, the subsequent histopathological patterns remain the same. The cutaneous tissue response to C. coronatus in both immunocompromised HIV-seronegative patients and immunocompetent patients typically reveals the presence of hyphal filaments and a granulomatous reaction encircled by eosinophilic deposits, known as the Splendore–Hoeppli phenomenon., In our studies, no typical hyphal filaments were observed in the dermal tissue sections. Other epidermal cellular responses included mild-to-moderate acanthosis, and the dermis exhibited dense neutrophilic, lymphocytic and eosinophilic infiltration. This histopathological pattern varies somewhat from previously published reports of C. coronatus infections in HIV-negative individuals.,,,, Repeated cultured biopsy specimens demonstrated the consistent growth of C. coronatus. Whether this atypical presentation of C. coronatus in the patient-derived tissue sections was due to the extremely low CD4+ count and heavy viral load or to other unknown reasons remains unclear. More investigations will be needed in similar case scenarios.
| ~ Conclusion|| |
To the best of our knowledge, there have not been any published reports of C. coronatus-related rhinoentomophthoromycosis infection, particularly in HIV/AIDS patients (resistant to first line ART). It is noteworthy that second-line ART augmented the antifungal activity of itraconazole against a C. coronatus-associated subcutaneous infection in an HIV-infected (AIDS) patient. The gradual resolution of the infected nasal lesion may be attributable to a reconstituted T cell (CD4+) immune response and dramatically reduced viral load. This study indicates how viral load testing can be used as a guide for clinical decisions, specifically on when to switch to second-line treatment and on how to optimize the duration of first-line treatment regimen. Additional observations are needed to evaluate the role of second-line ART-associated immune restoration and its plausible catalytic effect on antifungal drug (itraconazole) activity against C. coronatus in HIV-infected patients.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| ~ References|| |
Agrawal S, Meshram P, Qazi MS. Rhinoentomophthoromycosis: A rare case report. Indian J Med Microbiol 2013;31:401-3.
] [Full text]
Choon SE, Kang J, Neafie RC, Ragsdale B, Klassen-Fischer M, Carlson JA, et al.
Conidiobolomycosis in a young Malaysian woman showing chronic localized fibrosing leukocytoclastic vasculitis: A case report and meta-analysis focusing on clinicopathologic and therapeutic correlations with outcome. Am J Dermatopathol 2012;34:511-22.
Isa-Isa R, Arenas R, Fernández RF, Isa M. Rhinofacial conidiobolomycosis (entomophthoramycosis). Clin Dermatol 2012;30:409-12.
Thomas MM, Bai SM, Jayaprakash C, Jose P, Ebenezer R. Rhinoentomophthoromycosis. Indian J Dermatol Venereol Leprol 2006;72:296-9.
] [Full text]
Valle AC, Wanke B, Lazéra MS, Monteiro PC, Viegas ML. Entomophthoramycosis by Conidiobolus coronatus
. Report of a case successfully treated with the combination of itraconazole and fluconazole. Rev Inst Med Trop Sao Paulo 2001;43:233-6.
Loeffler J, Stevens DA. Antifungal drug resistance. Clin Infect Dis 2003;36:S31-41.
Antinori S, Nebuloni M, Magni C, Fasan M, Adorni F, Viola A, et al.
Trends in the postmortem diagnosis of opportunistic invasive fungal infections in patients with AIDS: A retrospective study of 1,630 autopsies performed between 1984 and 2002. Am J Clin Pathol 2009;132:221-7.
Chakrabarti A, Chatterjee SS, Shivaprakash MR. Overview of opportunistic fungal infections in India. Nihon Ishinkin Gakkai Zasshi 2008;49:165-72.
Mantadakis E, Samonis G. Clinical presentation of zygomycosis. Clin Microbiol Infect 2009;15 Suppl 5:15-20.
Kothavade RJ, Kura MM, Valand AG, Panthaki MH. Candida tropicalis: Its prevalence, pathogenicity and increasing resistance to fluconazole. J Med Microbiol 2010;59:873-80.
Neogi U, Heylen E, Shet A, Chandy S, Shamsunder R, Sönnerborg A, et al.
Long-term efficacy of first line antiretroviral therapy in Indian HIV-1 infected patients: A longitudinal cohort study. PLoS One 2013;8:e55421.
Orrell C, Harling G, Lawn SD, Kaplan R, McNally M, Bekker LG, et al.
Conservation of first-line antiretroviral treatment regimen where therapeutic options are limited. Antivir Ther 2007;12:83-8.
Nettles RE, Kieffer TL, Kwon P, Monie D, Han Y, Parsons T, et al.
Intermittent HIV-1 viremia (Blips) and drug resistance in patients receiving HAART. JAMA 2005;293:817-29.
Ormaasen V, Sandvik L, Dudman SG, Bruun JN. HIV related and non-HIV related mortality before and after the introduction of highly active antiretroviral therapy (HAART) in Norway compared to the general population. Scand J Infect Dis 2007;39:51-7.
Krentz HB, Kliewer G, Gill MJ. Changing mortality rates and causes of death for HIV-infected individuals living in Southern Alberta, Canada from 1984 to 2003. HIV Med 2005;6:99-106.
Sun HY, Chen MY, Hsiao CF, Hsieh SM, Hung CC, Chang SC, et al.
Endemic fungal infections caused by Cryptococcus neoformans
and Penicillium marneffei
in patients infected with human immunodeficiency virus and treated with highly active anti-retroviral therapy. Clin Microbiol Infect 2006;12:381-8.
Kothavade RJ, Oberai CM, Valand AG, Panthaki MH. Disseminated cryptococcosis and fluconazole resistant oral candidiasis in a patient with acquired immunodeficiency syndrome (AIDS). J Infect Dev Ctries 2010;4:674-8.
Thomas MM, Bai SM, Jayaprakash C, Jose P, Ebenezer R. Rhinoentomophthoromycosis. Indian J Dermatol Venereol Leprol 2006; 72: 296-299
Valle AC, Wanke B, Lazéra MS, Monteiro PC, Viegas ML. Entomophthoramycosis by Conidiobolus coronatus. Report of a case successfully treated with the combination of itraconazole and fluconazole. Rev Inst Med Trop Sao Paulo 2001; 43: 233-136.
Leopairut J, Larbcharoensub N, Cheewaruangroj W, Sungkanuparph S, Sathapatayavongs B. Rhinofacial entomophthoramycosis; a case series and review of the literature. Southeast Asian J Trop Med Public Health 2010;41:928-35.
Radhakrishnan N, Sachdeva A, Oberoi J, Yadav SP. Conidiobolomycosis in relapsed acute lymphoblastic leukemia. Pediatr Blood Cancer 2009;53:1321-3.
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