On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.79 no.3 Rio de Janeiro May/June 2004
Use of Ketoconazole for treating mucocutaneous Entomophthoromycosis: a case report*
Jackson M. L. CostaI; Luciola N. BarbosaII; Lucio Cristiano Paiva e PaivaII; Josélia L. NunesII; Sirlei G. MarquesIII; José Manuel M. RebeloIV; Ana Cristina R. SaldanhaV
IPh.D. in Medicine, Paulista School
of Medicine/ Federal University of São Paulo. Adjunct Professor in Medicine,
Federal University of Maranhão (UFMA/MA); and associate researcher at
the Gonçalo Moniz Research Center-FIOCRUZ, Bahia
IIM.D., Tropical Pathology Center, Federal University of Maranhão (UFMA/MA)
IIIMaster's Degree in Health and Environment, Federal University of Maranhão (UFMA/MA)
IVPh.D. in Sciences, University of São Paulo (USP/SP). Titular Professor of Biology, Federal University of Maranhão (UFMA/MA)
VMaster's Degree in Parasitic and Infectious Diseases Clinic, University of Brasilia (UnB). Researcher, Tropical Pathology Center, Federal University of Maranhão (UFMA/MA)
Entomophthoromycosis represents a clinical entity belonging to the group of zygomycoses, whose etiological agents are Conidiobolus coronatus, Conidiobolus incongruus and Basidiobolus ranarum. This paper describes the case of a 51-year-old male laborer with mucocutaneous entomophthoromycosis, who originates from the Amazon region of the State of Maranhão, Brazil. The diagnosis was established by anatomopathological examination one year after the onset of clinical manifestations. Treatment consisted of 400 mg daily (divided into two doses every 12 hours) of an imidazole derivative (ketoconazole®), which was tolerated well by the patient who showed a favorable response. The last assessment carried out 24 months after the beginning of treatment revealed that the patient was clinically cured.
Key words: diagnosis; clinical evolution; zygomycosis.
Entomophthoromycoses belong to a group of diseases caused by the fungi Conidiobolus coronatus, Conidiobolus incongruus and Basidiobolus ranarum.1,2,3 C. coronatus has been isolated in samples of soil and decaying vegetable matter. It is also able to parasitize several arthropod species.1 In males, the primary lesion occurs in the nasal mucosa. This is most likely the point-of-entry for the fungus as diffuse infiltration or polyps that prevent the passing of air. It propagates by the tissue adjacent to the nose and face (centrofacial zygomycosis), and sometimes by the nasopharynx and upper respiratory tract.4,5 The skin is slightly affected and ulceration hardly occurs, though edema with inflammatory characteristics may extend to the forehead, zygomas and lips. This in turn leads to disfiguring the patient's face, from slightly to severely.2,4,5
The infection caused by B. ranarum presents with an affection of the subcutaneous tissue with localized tumefaction on the thoracic region, extending to the throat and close to the lips. An invasion of the abdomen and thoracic cavity may occur as an extension of the subcutaneous tumoration. Recent case reports describe visceral manifestations affecting the gastrointestinal tract with tumorations that present with the signs and symptoms of acute abdomen.2,6
Renoirte et al.,7 in the Congo (Africa), and Bras et al.,4 in Jamaica (Central America) were simultaneously the first to describe the disease in humans. Presently, most of the cases reported come from the African continent, mainly Nigeria.1,6 In Brazil, the first case of the disease was described in the state of Bahia (Northeast Region).8 Later, cases were registered in other states from the same region (Maranhão, Piauí, Pernambuco and Sergipe), and more recently in Pará (North of Brazil).1,2,5,8-11
In this study, a case of mucocutaneous entomophthoromycosis endemic to the state of Maranhão, Brazil is presented. It was treated with an imidazole derivative (Ketoconazole®) and showed a good clinical response. We draw attention to the difficulties encountered in diagnosing the disease due especially to how rare the problem is.
A.P.S. is a 51 year-old Pardo male laborer from the municipality of Bela Vista in the Amazon region of the state of Maranhão, Brazil, where he has lived for 17 years. In January 1999, he complained of nasal obstruction (of the right nostril) with associated rhinorrhea. Colorless at the onset, it later progressed into a white-yellow secretion. It went on to show episodes of cephalea and epistaxis on the frontal region. A month after the initial manifestations, the patient sought medical care in his region. He was prescribed corticosteroid-based medication, and obtained slight improvement in the condition.
Subsequently, progressive respiratory difficulties evolved as the inflammatory process increased and extended to the cheekbone and upper lip region of this hemiface. A type of firm round and hard tumor could be perceived upon touching the affected area. As a result, there were alterations to the patient's physiognomic features (Figure 1). In June of the same year, he sought medical assistance again (with an otorhinolaryngologist, this time), and x-rays of the maxillary sinuses were solicited (with no alterations). The patient was submitted to a lesion scrape, which led to an alleviation of the obstructive condition.
In October, new tests were done (computerized tomography of the cranium), which revealed nasal obstruction of the nasal valve (Figure 2). In February 2000, biopsies of nasal mucosa and skin were submitted to Hospital Aldenora Belo (São Luis, MA). Its anatomopathologic diagnosis suggested a mycotic etiology. In March, the material collected from the nasal secretion (culture isolated Estafilococos aureus and Proteus sp) were then sent to this service, where it was reassessed, including the material from the anatomopathologic examination (which confirmed the diagnosis of nasofacial entomophthoromycosis) (Figure 3). The patient was submitted to treatment based on ketoconazole 44 mg daily for 12 months.
Course of the case - After a week of treatment, it was already possible to observe a regression of the edema, with improvement of the nasal obstruction, absence of rhinorrhea, epistaxis and cephalea. The patient was then advised to continue the treatment at home and return for a follow up at the outpatient's clinic at two-month intervals until completing 12 months. At the second assessment, there was evidence of the process improving and breathing returned to normal. This is associated with a regression of the obstructive process. At the nose examination, only discrete edema with inflammatory characteristics could be observed, indicating clear improvement of the initial condition. The patient was advised to continue taking the medication at the same dose. An appointment was set for his return at two-month intervals for renewed assessment of the condition (Figure 4).
By the end of the (12-month) treatment, the patient had found the lesion to have totally regressed. At the last assessment, 24 months after starting medication, the patient was clinically cured.
Entomophthoromycoses occur sporadically in tropical and subtropical regions of the American, African and Asian continents. There have been four forms reported of the disease's clinical presentation.
1) Subcutaneous - the lesions begin with small nodules evolving slowly and progressively; they grow firm, elastic, irregular and mobile over the deep planes to reach gigantic proportions, and are covered by the whole tegument. Its color is normal, and it most affects male children.
2) Subcutaneous/visceral - symptomatology depends on the intensity of the lesions and of the visceral organs involved, presenting with: weight loss, diarrhea, anorexia, dyspnea, and fever, difficulties in joint movement, adenopathy and thrombosis; overall, it is characterized by exuberant lesions.
3) Visceral or gastrointestinal - has a symptomatology related to the intensity of lesions and internal organs involved. Usually, it is combined with weight loss, vomiting, abdominal and thoracic pain, mucosanguinolent diarrhea, coughing without expectoration and, sometimes, complications like peritonitis and vena cava compression syndrome; usually affects children and adults indifferently.
4) Centrofacial - affects the nasolabial region starting with a condition of nasal obstruction, associated with rhinitis, epistaxis and cephalea, and progressing into facial edema. The lesions are characterized by hyperemia, edema, nodules and polyps. The nodules are firm, with defined borders. They adhere to the deep planes and show low mobility, are rarely exuberant and mainly affect individuals in adulthood.5,11,12, 14
In spite of the present patient's clinical presentation being characterized as a centrofacial form and the histopathological findings being quite suggestive of the disease, strengthening of the definitive diagnosis is only possible by isolating the fungus in a medium of appropriate culture. This could not be obtained because there was no growth of the fungus in a Sabouraud agar solution in the various attempts made at the service laboratory. To manage the case, the main differential diagnoses were taken into consideration, such as scleroma, rhinosporidiosis, malignant and benign tumors, paracoccidioidomycosis and American tegumentary leishmaniasis (the contiguous mucocutaneous form), bearing in mind that the latter two are considered endemic in the region from which the patient comes.13
In spite of potassium iodine being the treatment recommended for entomophthoromycoses, which usually has good response,14,15 some cases have been treated with other drugs, like amphotericin B in association with sulphamethoxazole-trimethoprim, 4.4-diaminodiphenyl sulfone, itraconazole, itraconazole-fluconazole, with good results.10,11,16-19
Costa et al.10 used 4.4-diaminodiphenyl sulfone (sulfona®) in two patients who were carriers of the disease. They initially had satisfactory response but during their gradual follow up, there was recurrence of the lesions. Later, these patients utilized Ketoconazole with excellent results. This fact was taken into consideration when deciding on the treatment to use for the patient studied, though there are also reports of a lack of success with this treatment on mucocutaneous entomophthoromycosis when used over a shorter period.11
In the present case, the scarcity of data in the literature regarding the disease may be the explanation for the delay in concluding the diagnosis. Case reports are few indeed, which may not correspond to the disease's reality in Brazil. Such a fact renders favorable the use of empirical therapy, in which the dose and time needed for treatment varies according to patients' clinical response.
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Jackson Mauricio Lopes Costa
Centro de Pesquisas Gonçalo Moniz - FIOCRUZ/Bahia
Rua Valdemar Falcão No 121 (Bairro Brotas)
CEP 41295-001 Salvador Bahia
Received in November, 20th of 2000.
Approved by the Consultive Council and accepted for publication in February, 27th of 2004.
* Work done at "the Tropical Pathology and Social Medicine Center of the Pathology Department, Federal University of Maranhão (UFMA)".