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Pharyngo-laryngeal histoplasmosis: one case in an immunocompetent child
International Journal of Pediatric Otorhinolaryngology 45 (1998) 177 – 181
Case report
Pharyngo-laryngeal histoplasmosis: one case in an immunocompetent child T. Coiffier a,*, G. Roger a, L. Beust a, B. Quinet b, D. Adam c, B. Dupont d, E.N. Garabedian a a
Department of Pediatric ENT and Cer6ico-Facial Surgery, Trousseau Children’s Hospital, 28, a6. A. Netter, 75012 Paris, France b Department of Infectious Diseases, Trousseau Children’s Hospital, 28, a6. A. Netter, 75012 Paris, France c Department of Histopathology, Trousseau Children’s Hospital, 28, a6. A. Netter, 75012 Paris, France d Mycology Unit, Institut Pasteur, 209, rue de Vaugirard, 75015 Paris, France Received 25 March 1998; received in revised form 8 July 1998; accepted 12 July 1998
Abstract We report a very rare case of disseminated pharyngo-laryngeal histoplasmosis with systemic spread in a 10-year-old, immunocompetent child from Guyana. The main signs were a marked deterioration in his general condition, hepato-splenomegaly, multiple lymphadenopathy and ulcerated pharyngo-laryngeal lesions. The diagnosis was made from brushings of the ulcerative lesions, a lymph node biopsy and serological tests performed in the national reference center for histoplasmosis. The initial treatment was with amphotericin B, which was then replaced by oral itraconazole. We report here the main epidemiological, clinical and therapeutic characteristics. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Histoplasma; Histoplasmosis; Fungal diseases; Antifungal agents; Itraconazole
1. Introduction The enigmatic death of Howard Carter in 1922, several months after the discovery of Toutankha-
* Corresponding author. Tel.: + 33 144 736114; fax: + 33 144 736108; e-mail: [email protected]
mon’s tomb, followed by that of other archaeologists, gave rise to the legend of the ‘curse of the pharaohs’ because of the violation of the graves. It would seem that they were victims of Histoplasma capsulatum which is found in the guano of bats in the pyramids. The fungus was first isolated by Darling in 1906 from the men working on the Panama canal.
0165-5876/98/$ - see front matter © 1998 Elsevier Science Ireland Ltd. All rights reserved. PII S0165-5876(98)00099-8
178
T. Coiffier et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 177–181
Histoplasmosis is a systemic mycosis which is not rare in the Caribbean islands and in Guyana. Serious cases are increasingly reported due to the AIDS epidemic. The diagnosis may be delayed for a long period of time. We report a case of disseminated histoplasmosis in a non-immunodepressed child from Guyana who initially presented with bucco-pharyngeal lesions.
2. Clinical case Re´my H., a 10-year-old child from Guyana was referred to Trousseau’s Children Hospital in Paris in July 1996 for the diagnosis and treatment of a chronic pharyngitis progressing for 8 months, associated with a dry cough, nocturnal sweats, peaks of fever in the evening, cervical and axillary lymphadenopathy, hepato-splenomegaly, without any associated intestinal disturbances and a marked deterioration of his overall condition with weight loss of 6 kg, that is, 25% of his ideal body weight. On 24 July 1996, an ENT panendoscopy revealed ulcerated lesions on the tonsillar pillars, the soft palate, the posterior pharyngeal wall and the supraglottic larynx which had destroyed the
Fig. 1. Endoscopic view of soft palate and posterior pharyngeal wall lesions.
Fig. 2. Endoscopic view of supraglottic larynx lesions with epiglottic destruction.
upper half of the epiglottis (Figs. 1 and 2). Laboratory tests performed at the same time showed the presence of an inflammatory syndrome, with an anemia of chronic disease of 9.3 g/dl, an ESR of 62 mm in first hour and 92 during the second and a CRP of 70 mg/l. The serological tests for toxoplasmosis, infectious mononucleosis (IM test and Paul–Bunnel–Davidson test), syphilis, HIV12 and HTLV1-2 were negative in June 1996. A tuberculin skin test was negative. A chest X-ray showed a discrete right basal interstitial syndrome but the bronchoalveolar lavage was normal. A liver biopsy revealed the presence of granulomatous tissue. At the end of this first series of tests, the differential diagnosis included: tuberculosis, tropical mycosis, atypical mycobacterium, lymphoma and a systemic disease, such as periarteritis nodosa or sarcoidosis. On 25 July 1996, histoplasmosis due to H. capsulatum was diagnosed from lymph node imprints and direct slide examination of brushings from an oropharyngeal lesion. Numerous small, rounded structures within macrophages were also seen on the axillary lymph node and oropharyngeal biopsies, highly suggestive of histoplasmosis (Fig. 3). The cultures were positive within 8 days.
T. Coiffier et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 177–181
No yeasts could be detected on the blood smear, a bone marrow aspirate and biopsy and a second bronchoalveolar lavage. The serological tests using immuno-electro-osmophoresis, which had been performed in Guyana and sent to the national reference center for mycoses and antifungals at the Pasteur Institute in Paris, later confirmed the diagnosis with the detection of a specific M arc. No deficit of humoral or cellular immunity was found. A central line was inserted to allow treatment with amphotericin B at a dose of 0.5 and then 1 mg/kg for 15 days, with close surveillance of renal function, and parenteral nutrition. Treatment was continued with oral itraconazole (200 mg per day) for 6 months. After 15 days of treatment, the ENT examination showed a marked regression of the granulations and the patient had gained 4 kg in weight. The child was followed-up for 4 months after the start of the treatment but then, despite repeated reminders, he was lost to follow-up.
3. Discussion The causative agent of histoplasmosis is H. capsulatum, a dimorphic, saprophytic fungus found in the soil in its mycelium phase. It is responsible for deep mycoses in man in its yeast
Fig. 3. Cytologic examination of lymph node imprints. Rounded structures within macrophages cytoplasms (arrows), highly suggestive of histoplasmosis (Giemsa staining).
179
phase, being reactivated by body temperature after airway transmission. The main vectors are wild chickens, rodents and especially bats, via their excreta. There is no human transmission between individuals. H. duboisii, an African cousin of H. capsulatum, differs in its mode of transmission and clinical expression. The endemic zone of H. capsulatum mainly covers the south-central region of the United States, Central America, the Caribbean and a large part of South America. Sporadic cases have been reported in Africa and Asia. Eighty five percent of the population from the Ohio and Mississippi valleys have positive intradermal histoplasmin tests [1]. This test is positive in 5% of the population of school age in Martinique [2]. More cases are, however, reported in French Guyana [3]. Infection by Histoplasma affects the reticulo-endothelial system. In the majority of cases (95%), the primary infection is asymptomatic or produces a flu-like syndrome. Re-infections are frequent in endemic zones. Acute pulmonary histoplasmosis is the most frequent clinical form (90%), with a dry cough, malaise and multiple pulmonary infiltrates associated with hilar lymphadenopathy. This usually resolves without any treatment but leaves calcified pulmonary lesions. Disseminated forms are rare but serious. They occur either in children aged less than 2 years old, elderly people or in immunodeficient subjects, notably those suffering with AIDS [4]. Nevertheless, 20% of the disseminated forms appear in people who are apparently healthy at the time of a heavy inoculum [5]. Disseminated forms are diagnosed by positive cultures or histology performed on extra-pulmonary lesions. Acute, sub-acute and chronic forms exist [6,7]. The acute form can be rapidly lethal in the absence of treatment with septicemia, involvement of multiple organs and, in particular, adrenal insufficiency. It mainly occurs in subjects with AIDS with a CD4 count of B 200/mm3. In 1987, the Center of Disease Control in Atlanta included extrapulmonary histoplasmosis amongst the opportunist infections which define the onset of AIDS in a HIV seropositive patient [3]. A sub-
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T. Coiffier et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 177–181
acute form can present with systemic and hematological signs: a pulmonary syndrome simulating tuberculosis with a fever and mainly associated with extra-pulmonary — digestive, cutaneous, cardiac and meningo-encephalic lesions. The chronic form is characterized by a marked deterioration in the patient’s overall condition, the absence of pulmonary signs, an hepato-splenomegaly, lymphadenopathy and often ENT lesions. The discovery of lesions of the upper aero-digestive tracts is often the presenting feature (60%) and may remain the only localization for a long time [1,3,6,8]. These lesions can evoke tuberculosis, a cancer or sarcoidosis [7]. They are the result of hematogenous spread and are initially budding or wart-like and then evolve into ulcerating, indurated, painful lesions. The most frequent sites are, in decreasing order, the tongue, the palate, the buccal mucosa and the larynx. The main differences with respect to tuberculosis are the multiplicity of lesions, involvement of the anterior larynx, destruction of the epiglottis, the absence of nasal or otologic involvement and the limited size of the lymphadenopathy. As far as we are aware, this is the first reported case of chronic disseminated histoplasmosis in an immunocompetent child older than 2 years with oropharyngeal lesions. Disseminated histoplasmosis usually occurs in healthy children of less than 2 years (who have not yet achieved immunological maturity) or in older immunodepressed children [9,10]. A review of the literature by Leggiadro reported 48 cases of children aged less than 2 years [11]. Acute forms are often found in children. The subacute forms occur in one third of childhood cases, with oropharyngeal lesions in 25% of them, while chronic forms are extremely rare. The diagnosis is made in specialized laboratories by the identification of yeasts within histiocytes on direct examination of smears from ulcerating cutaneous or mucosal lesions, from bronchoalveolar lavage fluid, a bone marrow aspirate, a blood smear or a tissue biopsy [2,12]. Special stains can be helpful, such as, methenamine-silver, Wright-Giemsa or GomoriGrocott. Confirmation can be provided by culture on Sabouraud–chloramphenicol medium at 27°C
for 10–15 days. Certain specialized laboratories in the United States are able to reliably identify H. capsulatum antigens by RIA (radioimmunoassay) or PCR (polymerase chain reaction) [13,14]). Serological tests using immunodiffusion or ELISA can give false-positives due to cross reactivity and previous contact, and also false-negatives in the case of immunodeficiency. Their main role is in follow-up and the diagnosis of relapse [2]. Intradermal histoplasmin skin testing is only of epidemiological value. Pure pulmonary forms are not treated. Disseminated forms require parenteral antifungal treatment by amphotericin B with a dose of up to 35 mg/kg, followed by oral itraconazole at a dose of 400 mg/kg for several months, or for life in cases of AIDS [2,4,6,15–18]. A close surveillance of renal function is needed when administering amphotericin B. In adults, mild forms can be treated by itraconazole as first line treatment but this has not been validated in children.
4. Conclusion Disseminated histoplasmosis due to H. capsulatum is a deep mycosis which is often revealed by bucco-pharyngeal lesions. The other clinical signs are completely non-specific and this diagnosis must be systematically considered in endemic zones, such as the Caribbean islands and Guyana, as well as atypical mycobacterium, tuberculosis or neoplasia. Its incidence is sharply increasing, in correlation with the propagation of AIDS which favors the spread of this fungus. A disseminated form of the disease is possible in immunocompetent subjects, notably in endemic zones associated with massive exposure; however, this is exceptional in adolescents.
References [1] R.T. Sataloff, A. Wilborn, A. Prestipino, M. Hawkshaw, R.J. Heuer, J. Cohn, Histoplasmosis of the larynx, Am. J. Otol. 14 (1993) 199 – 205. [2] E. Drouhet, B. Dupont, Histoplasmoses et autres mycoses d’importation en 1989, Rev. Prat. 39 (1989) 1675 – 1682.
T. Coiffier et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 177–181 [3] Y.G. Couppie´, P. Del Giudice, H. Mille, T. Cuchet, D. Sainte-Marie, R. Pradinaud, Histoplasmose disse´mine´e: deux cas chez des patients infecte´s par le virus de l’immunode´ficience humaine en Guyane franc¸aise, Rev. Med. Intern. 16 (1995) 767–770. [4] D. Levy, J.L. Poirot, M. Marteau-miltgen, et al., Histoplasmose a` Histoplasma capsulatum et SIDA, Rev. Med. Intern. 16 (1995) 407–412. [5] R. Goodwin, J.E. Loyd, R.M. Des Prez, Histoplasmosis in normal hosts, Medicine 60 (1981) 231. [6] M.E. Gerber, J.D. Rosdeutscher, A.M. Seiden, T.A. Tami, Histoplasmosis: the otolaryngologist’s perspective, Laryngoscope 105 (1995) 919–923. [7] H.H. Boutros, R.B. Van Winckle, G.A. Evans, S.M. Wasan, Oral histoplasmosis masquerading as an invasive carcinoma, J. Oral Maxillofac. Surg. 53 (1995) 1110– 1114. [8] J.E. Demaldent, M. Gentilini, C. Amat, Y. Manahc, A propos d’un cas d’histoplasmose larynge´e, Ann. OtoLaryngol. 95 (1978) 287–293. [9] W.T. Hughes, Hematogenous histoplasmosis in the immunocompromised child, J. Pediatr. 105 (1984) 569. [10] D.W. Clapp, M.B. Leiman, Z. Brahmi, Immunoregulatory lymphocyte populations in disseminated histoplasmosis of infancy, J. Infect. Dis. 1 (1987) 687–688.
.
181
[11] R.J. Leggiadro, R.F. Barrett, W.T. Hughes, Disseminated histoplasmosis of infancy, Pediatr. Infect. Dis. J. 7 (1988) 799 – 805. [12] E. Drouhet, B. Dupont, Panorama des mycoses en otolaryngologie, Ann. Oto-Laryngol. 99 (1982) 517 – 525. [13] M. Fojtasek, M.B. Kleiman, P. Connolly-Stringfield, R. Blair, J. Wheat, The histoplasma capsulatum antigen assay in disseminated histoplasmosis in children, Pediatr. Infect. Dis. J. 13 (1994) 801 – 805. [14] L.J. Wheat, R.B. Kohler, R.P. Tewari, Diagnosis of disseminated histoplasmosis by detection of Histoplasma capsulatum antigen in serum and urine specimens, N. Engl. J. Med. 314 (1986) 83 – 88. [15] R.A. Goodwin, J.L. Shapiro, G.H. Thurman, Disseminated histoplasmosis: clinical and pathological correlations, Medicine 59 (1980) 1 – 33. [16] J. Wheat, Histoplasmosis: recognition and treatment, Clin. Infect. Dis. 19 (1994) 19 – 27. [17] O. Lortholary, L. Guillevin, B. Dupont, E. Drouhet, Traitement des histoplasmoses et de la coccidioidomycose, Med. Mal. Infect. 25 (1995) 63 – 73. [18] A.M. Tobon, L. Franco, D. Espinal, I. Gomez, M. Arango, H. Trujillo, A. Restrepo, Disseminated histoplasmosis in children: the role of itraconazole therapy, Pediatr. Infect. Dis. J. 15 (1996) 1002 – 1008.
Case report
Pharyngo-laryngeal histoplasmosis: one case in an immunocompetent child T. Coiffier a,*, G. Roger a, L. Beust a, B. Quinet b, D. Adam c, B. Dupont d, E.N. Garabedian a a
Department of Pediatric ENT and Cer6ico-Facial Surgery, Trousseau Children’s Hospital, 28, a6. A. Netter, 75012 Paris, France b Department of Infectious Diseases, Trousseau Children’s Hospital, 28, a6. A. Netter, 75012 Paris, France c Department of Histopathology, Trousseau Children’s Hospital, 28, a6. A. Netter, 75012 Paris, France d Mycology Unit, Institut Pasteur, 209, rue de Vaugirard, 75015 Paris, France Received 25 March 1998; received in revised form 8 July 1998; accepted 12 July 1998
Abstract We report a very rare case of disseminated pharyngo-laryngeal histoplasmosis with systemic spread in a 10-year-old, immunocompetent child from Guyana. The main signs were a marked deterioration in his general condition, hepato-splenomegaly, multiple lymphadenopathy and ulcerated pharyngo-laryngeal lesions. The diagnosis was made from brushings of the ulcerative lesions, a lymph node biopsy and serological tests performed in the national reference center for histoplasmosis. The initial treatment was with amphotericin B, which was then replaced by oral itraconazole. We report here the main epidemiological, clinical and therapeutic characteristics. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Histoplasma; Histoplasmosis; Fungal diseases; Antifungal agents; Itraconazole
1. Introduction The enigmatic death of Howard Carter in 1922, several months after the discovery of Toutankha-
* Corresponding author. Tel.: + 33 144 736114; fax: + 33 144 736108; e-mail: [email protected]
mon’s tomb, followed by that of other archaeologists, gave rise to the legend of the ‘curse of the pharaohs’ because of the violation of the graves. It would seem that they were victims of Histoplasma capsulatum which is found in the guano of bats in the pyramids. The fungus was first isolated by Darling in 1906 from the men working on the Panama canal.
0165-5876/98/$ - see front matter © 1998 Elsevier Science Ireland Ltd. All rights reserved. PII S0165-5876(98)00099-8
178
T. Coiffier et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 177–181
Histoplasmosis is a systemic mycosis which is not rare in the Caribbean islands and in Guyana. Serious cases are increasingly reported due to the AIDS epidemic. The diagnosis may be delayed for a long period of time. We report a case of disseminated histoplasmosis in a non-immunodepressed child from Guyana who initially presented with bucco-pharyngeal lesions.
2. Clinical case Re´my H., a 10-year-old child from Guyana was referred to Trousseau’s Children Hospital in Paris in July 1996 for the diagnosis and treatment of a chronic pharyngitis progressing for 8 months, associated with a dry cough, nocturnal sweats, peaks of fever in the evening, cervical and axillary lymphadenopathy, hepato-splenomegaly, without any associated intestinal disturbances and a marked deterioration of his overall condition with weight loss of 6 kg, that is, 25% of his ideal body weight. On 24 July 1996, an ENT panendoscopy revealed ulcerated lesions on the tonsillar pillars, the soft palate, the posterior pharyngeal wall and the supraglottic larynx which had destroyed the
Fig. 1. Endoscopic view of soft palate and posterior pharyngeal wall lesions.
Fig. 2. Endoscopic view of supraglottic larynx lesions with epiglottic destruction.
upper half of the epiglottis (Figs. 1 and 2). Laboratory tests performed at the same time showed the presence of an inflammatory syndrome, with an anemia of chronic disease of 9.3 g/dl, an ESR of 62 mm in first hour and 92 during the second and a CRP of 70 mg/l. The serological tests for toxoplasmosis, infectious mononucleosis (IM test and Paul–Bunnel–Davidson test), syphilis, HIV12 and HTLV1-2 were negative in June 1996. A tuberculin skin test was negative. A chest X-ray showed a discrete right basal interstitial syndrome but the bronchoalveolar lavage was normal. A liver biopsy revealed the presence of granulomatous tissue. At the end of this first series of tests, the differential diagnosis included: tuberculosis, tropical mycosis, atypical mycobacterium, lymphoma and a systemic disease, such as periarteritis nodosa or sarcoidosis. On 25 July 1996, histoplasmosis due to H. capsulatum was diagnosed from lymph node imprints and direct slide examination of brushings from an oropharyngeal lesion. Numerous small, rounded structures within macrophages were also seen on the axillary lymph node and oropharyngeal biopsies, highly suggestive of histoplasmosis (Fig. 3). The cultures were positive within 8 days.
T. Coiffier et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 177–181
No yeasts could be detected on the blood smear, a bone marrow aspirate and biopsy and a second bronchoalveolar lavage. The serological tests using immuno-electro-osmophoresis, which had been performed in Guyana and sent to the national reference center for mycoses and antifungals at the Pasteur Institute in Paris, later confirmed the diagnosis with the detection of a specific M arc. No deficit of humoral or cellular immunity was found. A central line was inserted to allow treatment with amphotericin B at a dose of 0.5 and then 1 mg/kg for 15 days, with close surveillance of renal function, and parenteral nutrition. Treatment was continued with oral itraconazole (200 mg per day) for 6 months. After 15 days of treatment, the ENT examination showed a marked regression of the granulations and the patient had gained 4 kg in weight. The child was followed-up for 4 months after the start of the treatment but then, despite repeated reminders, he was lost to follow-up.
3. Discussion The causative agent of histoplasmosis is H. capsulatum, a dimorphic, saprophytic fungus found in the soil in its mycelium phase. It is responsible for deep mycoses in man in its yeast
Fig. 3. Cytologic examination of lymph node imprints. Rounded structures within macrophages cytoplasms (arrows), highly suggestive of histoplasmosis (Giemsa staining).
179
phase, being reactivated by body temperature after airway transmission. The main vectors are wild chickens, rodents and especially bats, via their excreta. There is no human transmission between individuals. H. duboisii, an African cousin of H. capsulatum, differs in its mode of transmission and clinical expression. The endemic zone of H. capsulatum mainly covers the south-central region of the United States, Central America, the Caribbean and a large part of South America. Sporadic cases have been reported in Africa and Asia. Eighty five percent of the population from the Ohio and Mississippi valleys have positive intradermal histoplasmin tests [1]. This test is positive in 5% of the population of school age in Martinique [2]. More cases are, however, reported in French Guyana [3]. Infection by Histoplasma affects the reticulo-endothelial system. In the majority of cases (95%), the primary infection is asymptomatic or produces a flu-like syndrome. Re-infections are frequent in endemic zones. Acute pulmonary histoplasmosis is the most frequent clinical form (90%), with a dry cough, malaise and multiple pulmonary infiltrates associated with hilar lymphadenopathy. This usually resolves without any treatment but leaves calcified pulmonary lesions. Disseminated forms are rare but serious. They occur either in children aged less than 2 years old, elderly people or in immunodeficient subjects, notably those suffering with AIDS [4]. Nevertheless, 20% of the disseminated forms appear in people who are apparently healthy at the time of a heavy inoculum [5]. Disseminated forms are diagnosed by positive cultures or histology performed on extra-pulmonary lesions. Acute, sub-acute and chronic forms exist [6,7]. The acute form can be rapidly lethal in the absence of treatment with septicemia, involvement of multiple organs and, in particular, adrenal insufficiency. It mainly occurs in subjects with AIDS with a CD4 count of B 200/mm3. In 1987, the Center of Disease Control in Atlanta included extrapulmonary histoplasmosis amongst the opportunist infections which define the onset of AIDS in a HIV seropositive patient [3]. A sub-
180
T. Coiffier et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 177–181
acute form can present with systemic and hematological signs: a pulmonary syndrome simulating tuberculosis with a fever and mainly associated with extra-pulmonary — digestive, cutaneous, cardiac and meningo-encephalic lesions. The chronic form is characterized by a marked deterioration in the patient’s overall condition, the absence of pulmonary signs, an hepato-splenomegaly, lymphadenopathy and often ENT lesions. The discovery of lesions of the upper aero-digestive tracts is often the presenting feature (60%) and may remain the only localization for a long time [1,3,6,8]. These lesions can evoke tuberculosis, a cancer or sarcoidosis [7]. They are the result of hematogenous spread and are initially budding or wart-like and then evolve into ulcerating, indurated, painful lesions. The most frequent sites are, in decreasing order, the tongue, the palate, the buccal mucosa and the larynx. The main differences with respect to tuberculosis are the multiplicity of lesions, involvement of the anterior larynx, destruction of the epiglottis, the absence of nasal or otologic involvement and the limited size of the lymphadenopathy. As far as we are aware, this is the first reported case of chronic disseminated histoplasmosis in an immunocompetent child older than 2 years with oropharyngeal lesions. Disseminated histoplasmosis usually occurs in healthy children of less than 2 years (who have not yet achieved immunological maturity) or in older immunodepressed children [9,10]. A review of the literature by Leggiadro reported 48 cases of children aged less than 2 years [11]. Acute forms are often found in children. The subacute forms occur in one third of childhood cases, with oropharyngeal lesions in 25% of them, while chronic forms are extremely rare. The diagnosis is made in specialized laboratories by the identification of yeasts within histiocytes on direct examination of smears from ulcerating cutaneous or mucosal lesions, from bronchoalveolar lavage fluid, a bone marrow aspirate, a blood smear or a tissue biopsy [2,12]. Special stains can be helpful, such as, methenamine-silver, Wright-Giemsa or GomoriGrocott. Confirmation can be provided by culture on Sabouraud–chloramphenicol medium at 27°C
for 10–15 days. Certain specialized laboratories in the United States are able to reliably identify H. capsulatum antigens by RIA (radioimmunoassay) or PCR (polymerase chain reaction) [13,14]). Serological tests using immunodiffusion or ELISA can give false-positives due to cross reactivity and previous contact, and also false-negatives in the case of immunodeficiency. Their main role is in follow-up and the diagnosis of relapse [2]. Intradermal histoplasmin skin testing is only of epidemiological value. Pure pulmonary forms are not treated. Disseminated forms require parenteral antifungal treatment by amphotericin B with a dose of up to 35 mg/kg, followed by oral itraconazole at a dose of 400 mg/kg for several months, or for life in cases of AIDS [2,4,6,15–18]. A close surveillance of renal function is needed when administering amphotericin B. In adults, mild forms can be treated by itraconazole as first line treatment but this has not been validated in children.
4. Conclusion Disseminated histoplasmosis due to H. capsulatum is a deep mycosis which is often revealed by bucco-pharyngeal lesions. The other clinical signs are completely non-specific and this diagnosis must be systematically considered in endemic zones, such as the Caribbean islands and Guyana, as well as atypical mycobacterium, tuberculosis or neoplasia. Its incidence is sharply increasing, in correlation with the propagation of AIDS which favors the spread of this fungus. A disseminated form of the disease is possible in immunocompetent subjects, notably in endemic zones associated with massive exposure; however, this is exceptional in adolescents.
References [1] R.T. Sataloff, A. Wilborn, A. Prestipino, M. Hawkshaw, R.J. Heuer, J. Cohn, Histoplasmosis of the larynx, Am. J. Otol. 14 (1993) 199 – 205. [2] E. Drouhet, B. Dupont, Histoplasmoses et autres mycoses d’importation en 1989, Rev. Prat. 39 (1989) 1675 – 1682.
T. Coiffier et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 177–181 [3] Y.G. Couppie´, P. Del Giudice, H. Mille, T. Cuchet, D. Sainte-Marie, R. Pradinaud, Histoplasmose disse´mine´e: deux cas chez des patients infecte´s par le virus de l’immunode´ficience humaine en Guyane franc¸aise, Rev. Med. Intern. 16 (1995) 767–770. [4] D. Levy, J.L. Poirot, M. Marteau-miltgen, et al., Histoplasmose a` Histoplasma capsulatum et SIDA, Rev. Med. Intern. 16 (1995) 407–412. [5] R. Goodwin, J.E. Loyd, R.M. Des Prez, Histoplasmosis in normal hosts, Medicine 60 (1981) 231. [6] M.E. Gerber, J.D. Rosdeutscher, A.M. Seiden, T.A. Tami, Histoplasmosis: the otolaryngologist’s perspective, Laryngoscope 105 (1995) 919–923. [7] H.H. Boutros, R.B. Van Winckle, G.A. Evans, S.M. Wasan, Oral histoplasmosis masquerading as an invasive carcinoma, J. Oral Maxillofac. Surg. 53 (1995) 1110– 1114. [8] J.E. Demaldent, M. Gentilini, C. Amat, Y. Manahc, A propos d’un cas d’histoplasmose larynge´e, Ann. OtoLaryngol. 95 (1978) 287–293. [9] W.T. Hughes, Hematogenous histoplasmosis in the immunocompromised child, J. Pediatr. 105 (1984) 569. [10] D.W. Clapp, M.B. Leiman, Z. Brahmi, Immunoregulatory lymphocyte populations in disseminated histoplasmosis of infancy, J. Infect. Dis. 1 (1987) 687–688.
.
181
[11] R.J. Leggiadro, R.F. Barrett, W.T. Hughes, Disseminated histoplasmosis of infancy, Pediatr. Infect. Dis. J. 7 (1988) 799 – 805. [12] E. Drouhet, B. Dupont, Panorama des mycoses en otolaryngologie, Ann. Oto-Laryngol. 99 (1982) 517 – 525. [13] M. Fojtasek, M.B. Kleiman, P. Connolly-Stringfield, R. Blair, J. Wheat, The histoplasma capsulatum antigen assay in disseminated histoplasmosis in children, Pediatr. Infect. Dis. J. 13 (1994) 801 – 805. [14] L.J. Wheat, R.B. Kohler, R.P. Tewari, Diagnosis of disseminated histoplasmosis by detection of Histoplasma capsulatum antigen in serum and urine specimens, N. Engl. J. Med. 314 (1986) 83 – 88. [15] R.A. Goodwin, J.L. Shapiro, G.H. Thurman, Disseminated histoplasmosis: clinical and pathological correlations, Medicine 59 (1980) 1 – 33. [16] J. Wheat, Histoplasmosis: recognition and treatment, Clin. Infect. Dis. 19 (1994) 19 – 27. [17] O. Lortholary, L. Guillevin, B. Dupont, E. Drouhet, Traitement des histoplasmoses et de la coccidioidomycose, Med. Mal. Infect. 25 (1995) 63 – 73. [18] A.M. Tobon, L. Franco, D. Espinal, I. Gomez, M. Arango, H. Trujillo, A. Restrepo, Disseminated histoplasmosis in children: the role of itraconazole therapy, Pediatr. Infect. Dis. J. 15 (1996) 1002 – 1008.