Diagnosis and Treatment of Conidiobolomycosis: A Review of 75 Cases from the Indian Subcontinent
Nitin Gupta1, Manish Soneja2
1 Senior Resident, Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
2 Associate Professor, Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
NAME, ADDRESS, E-MAIL ID OF THE CORRESPONDING AUTHOR: Dr. Manish Soneja, Associate Professor, Department of Medicine, Teaching Block, All India Institute of Medical Sciences, New Delhi-110029, India.
E-mail: manishsoneja@gmail.com
Introduction
Conidiobolomycosis is a subcutaneous rhinofacialzygomycosis caused by Conidiobolus spp. Its epidemiology in the Indian subcontinent is not well understood.
Aim
The aim of this study was epidemiological characterisation of conidiobolomycosis in the Indian subcontinent.
Materials and Methods
We conducted a review of literature using the terms “conidiobolomycosis”, “conidiobolus”, “entomophthoramycosis” and “entomophthoromycosis” in the Pubmed database combined with the following: India and publication language (English).
Results
A total of 75 cases of conidiobolomycosis were reported from 12 states of India, between October 1966 and December 2017, who presented with centrofacial swelling (males-62, females-13). The mean age of presentation was 35 years. Majority of the patients were immunocompetent with only one patient being immunosuppressed (acute leukaemia). A total of 21 patients were diagnosed only on the basis of culture, while the rest of them were diagnosed either on histopathology alone (n=33) or a combination of histopathology and culture (n=21). Saturated solution of potassium iodide (SSKI) was the most common drug (alone or in combination) used for treatment. Except one mortality, which was unrelated to the disease, all patients (n=56) responded to therapy.
Conclusion
Conidiobolomycosis is reported from most parts of the country, primarily in immunocompetent males and has an excellent response to anti-fungals.
Introduction
Conidiobolomycosis is a chronic subcutaneous rhino facial entomophthoramycosis [1]. Although, it is histopathologically indistinct from Basidiobolus spp., the other genera in the order entomphthorales, both of them are clinically and mycologically separate entities. There are three main species in the Conidiobolus genera-C.coronatus, C.incongruus and C. lamprauges. A new species, C.thermophilus has been isolated from the environment in India, but no human cases have been reported [2]. It is an uncommon disease, with few cases being reported from the tropical and subtropical zones of Africa, Asia and Americas [1]. The epidemiology of this disease in India is not well understood as most of the literature is in the form of case reports. Thus, the purpose of this study was to perform a systematic review of clinico-epidemiological characteristics of conidiobolomycosis cases from India.
Materials and Methods
We conducted a comprehensive search of English medical literature via the PubMed database to search for articles between October of 1966 and December of 2017. We used “conidiobolomycosis”, “conidiobolus”, “entomophthoramycosis” and “entomophthoromycosis” as the search terms. The search terms in the Medline database were combined with the following: India and publication language (English) and subject (human). The titles, affiliations, and abstracts of the selected articles were reviewed. Compatible clinical symptoms and either histopathology or culture positivity was taken as conidiobolomycosis. Those reports with at least the following details were included-state/region of residence where the case was reported, age, sex, immune status of the patient, diagnostic modality, treatment received and response to the treatment. Cases of mucormycosis, basidiobolomycosis and any other fungi were excluded. Repeated reports and non-case studies were excluded.
Results
A total of 307 articles were included for title/abstract screening. Out of this, 282 articles were excluded based on the inclusion and exclusion criteria. A total of 27 studies were included for full text review. A total of 75 cases of conidiobolomycosis were found who presented with centrofacial swelling [3-29]. Most number of cases were reported from West Bengal, Punjab, Delhi and Tamil Nadu. Male: female distribution was 62:13. The mean age of presentation was 35 (SD-14) years.
Majority of the patients were immunocompetent with only one patient being immunosuppressed (acute leukaemia) [7]. Most of the patients were diagnosed on histopathology alone (n=33) while culture alone was positive in 21 patients. Rest 21 patients were identified by a combination of histopathology and culture. Of the 58 patients, whose treatment details were known, only 22 patients were treated with monotherapy while the rest of 36 patients were treated with various combination of drugs. Majority of the patients responded to the therapy (n=56) with mortality reported in only one patient (Acute leukaemia patient) [7]. Follow-up details were not mentioned for 14 patients while four were lost to follow-up. The state-wise distribution is tabulated in [Table/Fig-1].
State wise distribution of cases of conidiobolomycosis from October 1966- December 2017 in India.
| State | No. | Gender | Age range (in years) | Diagnosis | Treatment | Follow-up |
|---|
| Himachal Pradesh [8] | 1 | M1 | 20 | C-1 | SK-1 | R-1 |
| Delhi [7,12,13,27,28] | 12 | M11, F1 | 1-70 | H-11, C 1 | A-1, AFSI-1, ASI-1, S-2, SI-2, K-1, SF-3, SK-1 | R-10, NR-1, LFU-1 |
| Punjab [9,11] | 15 | M13, F2 | 25-50 | H-10, H+C-5 | SI-10, S-1, NM-3, AK-1 | R-14, LFU-1 |
| Uttar Pradesh [11,21,22], | 4 | M4 | 16-50 | H-1, H+C-3 | ASI-1, S-1, A-1, SI-1 | R-4 |
| Uttarakhand [10] | 1 | M | 18 | H+C-1 | IT-1 | R-1 |
| Assam [11] | 1 | M | 27 | H+C-1 | SC-1 | R-1 |
| Orissa [5,19] | 2 | M2 | 19-45 | H+C-2 | S-1, SI-1 | R-2 |
| West Bengal [3,14-16] | 20 | M18, F2 | 20-65 | H-1, C-17, H+C-2 | SKC-1, SFKC-1, S-5, SK-2, SF-2, SI-1, NM-8 | R-12, NM-8 |
| Maharashtra [25] | 1 | M | 20 | H+C-1 | I-1 | R-1 |
| Karnataka [23,24,26] | 6 | M3, F3 | 22-50 | H-6 | I-1, A-1, C-1, NM-3 | R-2, LFU-1, NM-3 |
| Kerala [18] | 1 | M | 60 | H+C-1 | SF-1 | R-1 |
| Tamil Nadu [4,6,11,17,20,29] | 11 | M6, F5 | 15-55 | H-4, C-2, H+C-5 | IT-1, S-4, SC-2, F-1, NM-3 | R-7, LFU-1, NM-3 |
M: Male; F: Female; H: Histopathology; C: Culture; A: Amphotericin B; S: Saturated solution of potassium iodide; K: Ketoconazole; F: Fluconazole; I: Itraconazole; T: Terbinafine; C: Cotrimoxazole; R: Response present; NR: No response present; LFU: Loss to follow-up; NM: Not mentioned
Discussion
Conidiobolomycosis is a rare disease that has been reported from tropical areas around the world. A total of 75 cases were reported from India in a time span of over 50 years. It was reported from most parts of the country (12 states). The germination of Conidiobolus spp. requires high amount of humidity and this is probably the reason why majority of the cases were reported from the hot and humid states of West Bengal, Tamil Nadu and Punjab [1]. It is a chronic inflammatory granulomatous disease that involves the nasal mucosa and presents as nasal obstruction and centro-facial swelling of the nose [1]. It is seen in immunocompetent individuals and no known risk factors are described. Out of the 75 cases in our review, except one, all cases were immunocompetent [7]. It is hypothesised that the acquisition of spores of Conidiobolus spp. occurs via respiratory route or after minor trauma [1]. Males in the third and fourth decades of their life having more likelihood of being in contact with spores are most commonly affected [9,15,16].
Since, it is acquired by inhalation, the disease usually starts with the involvement of nasal cavity (unilateral to bilateral) and later extends to the surrounding area leading to facial swelling. The diagnosis of conidiobolomycosis is usually based on clinical presentation and the histopathology alone [27,28]. The culture of the causative fungus is confirmatory, although often unsuccessful. Most of the cultures was identified as C.coronatus, except one, which was identified as C.incongruus based on the culture and micro-morphological features (non-villose conidia) [8]. Histopathologically, aseptate hyphae along with granulomatous infiltrate consisting of eosinophils and multinucleated giant cells are seen. The star like eosinophilic projections has been described as Splendore hoeppli phenomenon [1]. Splendore hoeppli phenomenon is described with other fungal and parasitic diseases, but presence of aseptate hyphae along with this phenomenon is usually enough to make a diagnosis of entomophthoramycosis. Although, aseptate hyphae is also seen with mucormycosis, but splendore hoeppli phenomenon is rarely described in mucormycosis.
The treatment modalities include either surgical excision or medical treatment. In a meta-analysis by Choon SE et al., it was observed that, once diagnosed, conidiobolomycosis is a fairly easy disease to treat with a very good response rate (83%), irrespective of the anti-fungals used [30]. In the reported cases that we reviewed from India, most of the cases had good response with anti-fungals. We observed that SSKI followed by itraconazole were the most commonly used drug either alone or in combination. In absence of clinical trials comparing the efficacy of the drugs, it would be difficult to classify SSKI or itraconazole as the preferred drug for treatment [15]. Although, the response can be evident in as early as one week, the total duration of therapy has not been clearly defined.
Conclusion
Conidiobolomycosis should be considered among middle aged immunocompetent males, presenting with painless centrofacial swelling and symptoms of nasal obstruction. Culture or presence of aseptate hyphae and splendore hoeppli phenomenon on histopathology helps in clinching the diagnosis in most cases. It can be treated with azoles or SSKI with a good response rate. We report this review of literature to bring a rarely diagnosed but very easily treated fungus into the light from the Indian perspective.
M: Male; F: Female; H: Histopathology; C: Culture; A: Amphotericin B; S: Saturated solution of potassium iodide; K: Ketoconazole; F: Fluconazole; I: Itraconazole; T: Terbinafine; C: Cotrimoxazole; R: Response present; NR: No response present; LFU: Loss to follow-up; NM: Not mentioned
[1]. Shaikh N, Hussain KA, Petraitiene R, Schuetz AN, Walsh TJ, Entomophthoramycosis: A neglected tropical mycosis Clin Microbiol Infect 2016 22(8):688-94.10.1016/j.cmi.2016.04.00527109491 [Google Scholar] [CrossRef] [PubMed]
[2]. Waingankar VM, Singh SK, Srinivasan MC, A new thermophilic species of Conidiobolus from India Mycopathologia 2008 165(3):173-77.10.1007/s11046-007-9088-618266074 [Google Scholar] [CrossRef] [PubMed]
[3]. Dutta S, Sarkar S, Linka U, Dora S, Conidiobolomycosis: A case report of rare fungal infection from the eastern India Indian Dermatol Online J 2015 6(6):393-95.10.4103/2229-5178.16971526753137 [Google Scholar] [CrossRef] [PubMed]
[4]. Cherian L, Varghese L, Panchatcharam B, Parmar H, Varghese G, Nasal conidiobolomycosis: A successful treatment option for localized disease J Postgrad Med 2015 61(2):143-44.10.4103/0022-3859.15311225766357 [Google Scholar] [CrossRef] [PubMed]
[5]. Arora N, Bhargava EK, Rai V, Nasal conidiobolomycosis-The unknown threat J Clin Diagn Res 2016 10(12):MJ0110.7860/JCDR/2016/21480.894628208896 [Google Scholar] [CrossRef] [PubMed]
[6]. Krishnan SG, Sentamilselvi G, Kamalam A, Das KA, Janaki C, Entomophthoromycosis in India-A 4-year study Mycoses 1998 41(1-2):55-58.10.1111/j.1439-0507.1998.tb00377.x9610135 [Google Scholar] [CrossRef] [PubMed]
[7]. Radhakrishnan N, Sachdeva A, Oberoi J, Yadav SP, Conidiobolomycosis in relapsed acute lymphoblastic leukaemia Pediatr Blood Cancer 2009 53(7):1321-23.10.1002/pbc.2225919731329 [Google Scholar] [CrossRef] [PubMed]
[8]. Sharma NL, Mahajan VK, Singh P, Orofacial conidiobolomycosis due to Conidiobolus incongruus Mycoses 2003 46(3-4):137-40.10.1046/j.1439-0507.2003.00851.x12870203 [Google Scholar] [CrossRef] [PubMed]
[9]. Gupta M, Narang T, Kaur RJ, Manhas A, Saikia UN, Dogra S, A prospective case series evaluating efficacy and safety of combination of itraconazole and potassium iodide in rhinofacial conidiobolomycosis Int J Dermatol 2016 55(2):208-14.10.1111/ijd.1296626234812 [Google Scholar] [CrossRef] [PubMed]
[10]. Varshney S, Gupta P, Bist SS, Bhagat S, Conidiobolus coronatus granuloma of the right inferior turbinate: A rare presentation Ear Nose Throat J 2015 94(4-5):E32-35. [Google Scholar]
[11]. Chowdhary A, Randhawa HS, Khan ZU, Ahmad S, Khanna G, Gupta R, Rhinoentomophthoromycosis due to Conidiobolus coronatus. A case report and an overview of the disease in India Med Mycol 2010 48(6):870-79.10.3109/13693786.2010.48601020482451 [Google Scholar] [CrossRef] [PubMed]
[12]. Kabra SK, Jain Y, Sudhin T, Iyer KV, Ninan SA, Seth V, Successful treatment of entomophthoromycosis with itraconazole Indian Pediatr 1998 35(2):163-66. [Google Scholar]
[13]. Ramesh A, Deka RC, Vijayaraghavan M, Ray R, Kabra SK, Rakesh K, Entomophthoromycosis of the nose and paranasal sinus Indian J Pediatr 2000 67(4):307-10.10.1007/BF0275818210878876 [Google Scholar] [CrossRef] [PubMed]
[14]. Mukhopadhyay D, Ghosh LM, Thammayya A, Sanyal M, Entomophthoromycosis caused by Conidiobolus coronatus: Clinicomycological study of a case AurisNasus Larynx 1995 22(2):139-42.10.1016/S0385-8146(12)80113-1 [Google Scholar] [CrossRef]
[15]. Thammayya A, Zygomycosis due to Conidiobolus coronatus in west Bengal Indian J Chest Dis Allied Sci 2000 42(4):305-09. [Google Scholar]
[16]. Maiti PK, Bose R, Bandyopadhyay S, Bhattacharya S, Dey JB, Ray A, Entomophthoromycosis in South Bengal (Eastern India): A 9 years study Indian J Pathol Microbiol 2004 47(2):295-97. [Google Scholar]
[17]. Michael RC, Michael JS, Mathews MS, Rupa V, Unusual presentation of entomophthoromycosis Indian J Med Microbiol 2009 27(2):156-58.10.4103/0255-0857.4943219384042 [Google Scholar] [CrossRef] [PubMed]
[18]. Thomas MM, Bai SM, Jayaprakash C, Jose P, Ebenezer R, Rhinoentomophthoromycosis Indian J Dermatol Venereol Leprol 2006 72(4):296-99.10.4103/0378-6323.2672816880578 [Google Scholar] [CrossRef] [PubMed]
[19]. Tripathy S, Vijayashree J, Mishra M, Jena DK, Behera B, Mohapatra A, Rhinofacialzygomycosis successfully treated with oral saturated solution of potassium iodide: A case report J Eur Acad Dermatol Venereol 2007 21(1):117-19.10.1111/j.1468-3083.2006.01803.x17207186 [Google Scholar] [CrossRef] [PubMed]
[20]. John D, Irodi A, Michael JS, Concurrent infections of Conidiobolus coronatus with disseminated tuberculosis presenting as bilateral orbital cellulitis J Clin Diagn Res 2016 10(4):ND01-02.10.7860/JCDR/2016/16790.753527190852 [Google Scholar] [CrossRef] [PubMed]
[21]. Bhalla S, Srivastava VK, Gupta RK, Rhinofacial entomophthoramycosis: A rare fungal infection in an adolescent boy Indian Journal of Pathology and Microbiology 2015 58(3):40210.4103/0377-4929.16293326275280 [Google Scholar] [CrossRef] [PubMed]
[22]. Bhatia N, Singh C, Kawatra R, Alam S, Dhawan R, Rhinoentomophthoromycosis: rarity revisited Ear Nose Throat J 2010 89(6):268-71.10.1177/01455613100890060920556738 [Google Scholar] [CrossRef] [PubMed]
[23]. Pujary P, Pujary K, Mahesh SG, Valiathan M, Conidiobolus coronata granuloma of left inferior turbinate: a rare presentation J Laryngol Otol 2008 122(7):e1510.1017/S002221510800283118501040 [Google Scholar] [CrossRef] [PubMed]
[24]. Nayak DR, Pillai S, Rao L, Rhinofacial zygomycosis caused by Conidiobolus coronatus Indian J Otolaryngol Head Neck Surg 2004 56(3):225-27. [Google Scholar]
[25]. Agrawal S, Meshram P, Qazi MS, Rhinoentomophthoromycosis: A rare case report Indian J Med Microbiol 2013 31(4):401-03.10.4103/0255-0857.11886624064651 [Google Scholar] [CrossRef] [PubMed]
[26]. Bhat RM, Srinivas M, Sequeira F, Sukumar D, Swethadri GK, Rhinoentomophthoromycosis with mutilation Clin Exp Dermatol 2010 35(5):501-04.10.1111/j.1365-2230.2009.03687.x19886966 [Google Scholar] [CrossRef] [PubMed]
[27]. Ramesh V, Ramam M, Capoor MR, Sugandhan S, Dhawan J, Khanna G, Subcutaneous zygomycosis: report of 10 cases from two institutions in North India J Eur Acad Dermatol Venereol 2010 24(10):1220-25.10.1111/j.1468-3083.2010.03606.x20202057 [Google Scholar] [CrossRef] [PubMed]
[28]. Thakar A, Baruah P, Kumar S, Sharma MC, Rhinophycomycosis J Laryngol Otol 2001 115(6):493-96.10.1258/002221501190802711429077 [Google Scholar] [CrossRef] [PubMed]
[29]. Balraj A, Anandi V, Raman R, Nasofacial conidiobolomycosis Ear Nose Throat J 1991 70(10):737-39. [Google Scholar]
[30]. Choon SE, Kang J, Neafie RC, Ragsdale B, Klassen-Fischer M, Carlson JA, 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(5):511-22.10.1097/DAD.0b013e31823db5c122728716 [Google Scholar] [CrossRef] [PubMed]