Case report
A case of disseminated histoplasmosis diagnosed after oral presentation in an old HIV-negative patient in Sweden €rvi2, Go € ran Roos3 and Karin Nylander3 Fernando J. Mota de Almeida1, Kristina Kivija 1
Department of Endodontics, Tandv ardenskompetenscentrum, Lule a, Sweden; 2Department of Oral and Maxillofacial Surgery, Sunderby a University, Ume a, Sweden Hospital, Lule a, Sweden; 3Department of Medical Biosciences, Ume
doi:10.1111/ger.12150 A case of disseminated histoplasmosis diagnosed after oral presentation in an old HIV-negative patient in Sweden Histoplasmosis is an endemic disease in various regions such as North America and South-East Asia but remains rare in Europe. Disseminated histoplasmosis is unusual in HIV-negative patients. Here, we describe a case of disseminated histoplasmosis in an HIV-negative patient diagnosed after oral presentation. Keywords: histoplasmosis, Sweden, Mouth. Accepted 1 August 2014
Introduction Histoplasmosis is an endemic mycosis caused by the dimorphic fungus Histoplasma capsulatum occurring in various regions of the world predominantly in North and Central America, where it was discovered a century ago.1 Cases have been reported also outside the endemic areas, including several European countries. Due to worldwide travelling, it is becoming an emerging infection.2– 4
Histoplasmosis is primarily a pulmonary disease and infection occurs during activities disrupting the soil or accumulated guano from birds and bats. Immunosuppressed patients, especially patients with AIDS, are at risk of developing the disseminated form.1 Here, we present a case of disseminated histoplasmosis in an old HIV-negative patient in northern Sweden diagnosed after oral presentation.
Case report In January 2011, an 83-year-old man was referred to the dental clinic at Sunderby Hospital, Lule a, Sweden, due to oral ulceration. The patient complained of severe pain while eating. He also had more generalised symptoms such as cough, hoarseness and a feeling of feebleness which all started in November 2010. At that time, he had severe gingivitis and treatment for necrotizing 234
ulcerative gingivitis was started including debridation combined with preoperative 1600 mg of metronidazole and completed with 400 mg of metronidazole three times per day under 10 days. No effect was, however, seen and the patient’s condition worsened and he began losing his appetite. Lesions then spread to nearby surfaces and the patient experienced extreme oral pain. A biopsy from the soft tissue around the mucogingival line of the lower jaw in the midline was taken in December 2010 by the referring dentist. The clinical view at the time of biopsy is shown in Fig. 1. The biopsy showed unspecific morphologic changes. In January 2011, at the first examination in the hospital, there were ulcerations in the buccal and lingual gingiva of the upper jaw (Fig. 2a) almost reaching the soft palate. Ulcers were also affecting the buccal gingiva of the lower jaw (Fig. 2b). In addition, there was massive food impaction, calculus and plaque and a severe foeter ex ore. Palliative treatment with local anaesthetic rinse, local corticosteroids and sunflower oil was initiated and conservative periodontal treatment started, with an almost daily visit to the oral hygienist to minimise the inflammatory burden. The patient had controlled high blood pressure, insulin treated diabetes mellitus and an aorta aneurysm that did not warrant medical care. He was also diagnosed with prostate cancer in 2005 and treated conservatively with hormones and
© 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd, Gerodontology 2015; 32: 234–236
Oral histoplasmosis case in Sweden
sion. Lesions were now also present on the right forearm proximal to the wrist (Fig. 2c). A second biopsy taken from the vestibular mucosa showed macrophages with intracellular microorganisms, suggestive of H. capsulatum (Fig. 2d,e). A third oral biopsy was then taken for microbiological examination in early March and an aspirate from the forearm in late March. For microbiological analysis, specimens were cultured onto Mycosel agar (BD) and potato glucose agar (BD) slopes and into Sabouraud’s glucose broth (BD). Cultures were incubated at 30°C for 4 weeks and examined weekly for fungal growth. H. capsulatum was identified by the characteristic tuberculate macroconidia seen at microscopic examination of the formalin killed culture. The patient was accordingly diagnosed with disseminated histoplasmosis. Further medical investigation could not detect other sites of infection apart from the oral cavity and skin. The kidney biopsy was re-evaluated showing no signs H. capsulatum. The patient was HIV negative. Antibiotic therapy with intravenous amphotericin B 100 mg/day was started, the prednisolone dose reduced to 5 mg/day and the patient showed good improvement. Amphotericin B was replaced after 3 weeks by 200 mg of itraconazole three times a day under 3 days and then to a dose of 200 mg of itraconazole twice a day under 12 months. By Mars 2011, the prednisolone was adjusted to 2.5 mg/day until today.
Figure 1 Clinical photo at the time of the first biopsy in December 2010.
intermittent catheterisation. During the summer, in 2009, he had frequent urinary tract infections. In July 2010, the patient became ill, and a renal biopsy gave the diagnosis sarcoidosis. The patient was then put on a high prednisolone therapy of 50 mg/day. His general health improved for a few months before worsening in late November 2010. By that time, the prednisolone dose had been successively reduced to 20 mg/day. He also suffered from several episodes of fever, symptoms for which he was being followed at the hospital. As the situation worsened and eating became increasingly difficult because of the pain, he was admitted to the hospital in February where a nasogastric tube was inserted 2 weeks after admis-
(a)
(c)
235
(b)
(d)
(e)
Figure 2 Buccal gingiva of the upper jaw (a), gingiva in the mandible (b), swelling of the right forearm (c) observed at the hospital after periodontal treatment was started. Histological section showing macrophages with intracellular microorganisms, haematoxylin/eosin staining (d) and PAS-staining (e). © 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd, Gerodontology 2015; 32: 234–236
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The oral and skin lesions healed, and the patient was discharged from the hospital in April 2011 followed by regular controls till the end of 2011. Further medical investigation could not detect other sites of infection apart from the oral cavity and skin. The kidney biopsy was re-evaluated showing no signs H. capsulatum. The patient was HIV negative.
Discussion The first case histoplasmosis reported in Sweden was in a patient with AIDS in 1989.5 Between 1999 and 2012, eight cases have been reported at Karolinska University Laboratory, Stockholm (E. Chryssanthou, personal communication) which is the only microbiology laboratory with facilities for detection of histoplasmosis in Sweden. An European survey during 6 years in the 90s detected 118 cases. Even if that study could not determine the true incidence, histoplasmosis remains a rarely diagnosed condition in Europe.6 Histoplasmosis is primarily a pulmonary disease and most infected patients have haematogenous dissemination through parasitised macrophages. The immune system may eventually control the infection but some foci of H. capsulatum can remain viable, and reactivation of the infection can occur several years later usually after cell-
References 1. Kauffman CA. Histoplasmosis: a clinical and laboratory update. Clin Microbiol Rev 2007; 20: 115–32. 2. Torres-Rodriguez JM, SeguraRoca G, Coll J. [Histoplasmosis 45 years after infection in an immunocompetent man]. Rev Iberoam Micol 2009; 26: 244–6. 3. Salomon J, Flament Saillour M, De Truchis P, Bougnoux ME, Dromer F, Dupont B et al. An outbreak of acute pulmonary histoplasmosis in members of a trekking trip in Martinique, French West Indies. J Travel Med 2003; 10: 87–93. 4. Gascon J, Torres JM, Luburich P, Ayuso JR, Xaubet A, Corachan M. Imported histoplasmosis in Spain. J Travel Med 2000; 7: 89–91. 5. Petrini B, Gyllensten K, JorupRonstrom C, von Rosen ML. [The first case of generalized histoplasmosis in a patient with AIDS in
mediated immunosuppression1,2 and long periods of latency, up to 50 years, have been reported.2,6 As the fungus is not endemic in Sweden, the most probable source of infection of this patient was Thailand, an endemic zone for H. capsulatum, where he was on holiday in 2007 and 2008.7–9 At the initial infection, he most likely developed symptoms similar to those of influenza within the first weeks.3 The fungus remained viable and when the patient became immunosuppressed in 2010, it was reactivated.1,2,6 The patient was HIV negative, but was on corticosteroids, a therapy which is a risk factor for the disseminated form of histoplasmosis.1 Our patient severely worsened a few months after receiving corticosteroids for the previously diagnosed sarcoidosis. As there is a risk for confusion between histoplasmosis and sarcoidosis,10 re-evaluation of the kidney biopsy was performed, however, without detection of any fungi. Oral manifestations can be seen in an isolated form but are more frequently observed in the disseminated form.1,9 Disseminated histoplasmosis is a difficult diagnosis to make especially in non-endemic areas. This report can hopefully encourage clinicians from non-endemic areas to consider histoplasmosis in cases of non-remitting oral ulcers, as this disease can occur in non-HIV patients long after they have visited an endemic zone.
Sweden]. Lakartidningen 1989; 86: 4101–2. 6. Ashbee HR, Evans EG, Viviani MA, Dupont B, Chryssanthou E, Surmont I et al. Histoplasmosis in Europe: report on an epidemiological survey from the European Confederation of Medical Mycology Working Group. Med Mycol 2008; 46: 57–65. 7. Chetchotisakd P, Kiertiburanakul S, Mootsikapun P, Assanasen S, Chaiwarith R, Anunnatsiri S. Disseminated nontuberculous mycobacterial infection in patients who are not infected with HIV in Thailand. Clin Infect Dis 2007; 45: 421–7. 8. Poonwan N, Imai T, Mekha N, Yazawa K, Mikami Y, Ando A et al. Genetic analysis of Histoplasma capsulatum strains isolated from clinical specimens in Thailand by a PCRbased random amplified polymorphic DNA method. J Clin Microbiol 1998; 36: 3073–6.
9. Poinsilpa KP, Tantawichien T. Disseminated histoplasmosis in a young Thai male. J Travel Med 1994; 1: 57. 10. Walker JV, Baran D, Yakub N, Freeman RB. Histoplasmosis with hypercalcemia, renal failure, and papillary necrosis. Confusion with sarcoidosis. JAMA 1977; 237: 1350–2.
Correspondence to: Fernando J. Mota de Almeida, Department of Endodontics, Tandv ardenskompetencentrum, Skeppsbrogatan 22, Box 922, SE-971 28 Lule a, Sweden. Tel.: +46-920-71974 Fax: +46-920-71 704 E-mail: fernando.mota-de-almeida @nll.se
© 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd, Gerodontology 2015; 32: 234–236
A case of disseminated histoplasmosis diagnosed after oral presentation in an old HIV-negative patient in Sweden €rvi2, Go € ran Roos3 and Karin Nylander3 Fernando J. Mota de Almeida1, Kristina Kivija 1
Department of Endodontics, Tandv ardenskompetenscentrum, Lule a, Sweden; 2Department of Oral and Maxillofacial Surgery, Sunderby a University, Ume a, Sweden Hospital, Lule a, Sweden; 3Department of Medical Biosciences, Ume
doi:10.1111/ger.12150 A case of disseminated histoplasmosis diagnosed after oral presentation in an old HIV-negative patient in Sweden Histoplasmosis is an endemic disease in various regions such as North America and South-East Asia but remains rare in Europe. Disseminated histoplasmosis is unusual in HIV-negative patients. Here, we describe a case of disseminated histoplasmosis in an HIV-negative patient diagnosed after oral presentation. Keywords: histoplasmosis, Sweden, Mouth. Accepted 1 August 2014
Introduction Histoplasmosis is an endemic mycosis caused by the dimorphic fungus Histoplasma capsulatum occurring in various regions of the world predominantly in North and Central America, where it was discovered a century ago.1 Cases have been reported also outside the endemic areas, including several European countries. Due to worldwide travelling, it is becoming an emerging infection.2– 4
Histoplasmosis is primarily a pulmonary disease and infection occurs during activities disrupting the soil or accumulated guano from birds and bats. Immunosuppressed patients, especially patients with AIDS, are at risk of developing the disseminated form.1 Here, we present a case of disseminated histoplasmosis in an old HIV-negative patient in northern Sweden diagnosed after oral presentation.
Case report In January 2011, an 83-year-old man was referred to the dental clinic at Sunderby Hospital, Lule a, Sweden, due to oral ulceration. The patient complained of severe pain while eating. He also had more generalised symptoms such as cough, hoarseness and a feeling of feebleness which all started in November 2010. At that time, he had severe gingivitis and treatment for necrotizing 234
ulcerative gingivitis was started including debridation combined with preoperative 1600 mg of metronidazole and completed with 400 mg of metronidazole three times per day under 10 days. No effect was, however, seen and the patient’s condition worsened and he began losing his appetite. Lesions then spread to nearby surfaces and the patient experienced extreme oral pain. A biopsy from the soft tissue around the mucogingival line of the lower jaw in the midline was taken in December 2010 by the referring dentist. The clinical view at the time of biopsy is shown in Fig. 1. The biopsy showed unspecific morphologic changes. In January 2011, at the first examination in the hospital, there were ulcerations in the buccal and lingual gingiva of the upper jaw (Fig. 2a) almost reaching the soft palate. Ulcers were also affecting the buccal gingiva of the lower jaw (Fig. 2b). In addition, there was massive food impaction, calculus and plaque and a severe foeter ex ore. Palliative treatment with local anaesthetic rinse, local corticosteroids and sunflower oil was initiated and conservative periodontal treatment started, with an almost daily visit to the oral hygienist to minimise the inflammatory burden. The patient had controlled high blood pressure, insulin treated diabetes mellitus and an aorta aneurysm that did not warrant medical care. He was also diagnosed with prostate cancer in 2005 and treated conservatively with hormones and
© 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd, Gerodontology 2015; 32: 234–236
Oral histoplasmosis case in Sweden
sion. Lesions were now also present on the right forearm proximal to the wrist (Fig. 2c). A second biopsy taken from the vestibular mucosa showed macrophages with intracellular microorganisms, suggestive of H. capsulatum (Fig. 2d,e). A third oral biopsy was then taken for microbiological examination in early March and an aspirate from the forearm in late March. For microbiological analysis, specimens were cultured onto Mycosel agar (BD) and potato glucose agar (BD) slopes and into Sabouraud’s glucose broth (BD). Cultures were incubated at 30°C for 4 weeks and examined weekly for fungal growth. H. capsulatum was identified by the characteristic tuberculate macroconidia seen at microscopic examination of the formalin killed culture. The patient was accordingly diagnosed with disseminated histoplasmosis. Further medical investigation could not detect other sites of infection apart from the oral cavity and skin. The kidney biopsy was re-evaluated showing no signs H. capsulatum. The patient was HIV negative. Antibiotic therapy with intravenous amphotericin B 100 mg/day was started, the prednisolone dose reduced to 5 mg/day and the patient showed good improvement. Amphotericin B was replaced after 3 weeks by 200 mg of itraconazole three times a day under 3 days and then to a dose of 200 mg of itraconazole twice a day under 12 months. By Mars 2011, the prednisolone was adjusted to 2.5 mg/day until today.
Figure 1 Clinical photo at the time of the first biopsy in December 2010.
intermittent catheterisation. During the summer, in 2009, he had frequent urinary tract infections. In July 2010, the patient became ill, and a renal biopsy gave the diagnosis sarcoidosis. The patient was then put on a high prednisolone therapy of 50 mg/day. His general health improved for a few months before worsening in late November 2010. By that time, the prednisolone dose had been successively reduced to 20 mg/day. He also suffered from several episodes of fever, symptoms for which he was being followed at the hospital. As the situation worsened and eating became increasingly difficult because of the pain, he was admitted to the hospital in February where a nasogastric tube was inserted 2 weeks after admis-
(a)
(c)
235
(b)
(d)
(e)
Figure 2 Buccal gingiva of the upper jaw (a), gingiva in the mandible (b), swelling of the right forearm (c) observed at the hospital after periodontal treatment was started. Histological section showing macrophages with intracellular microorganisms, haematoxylin/eosin staining (d) and PAS-staining (e). © 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd, Gerodontology 2015; 32: 234–236
236
F. J. Mota de Almeida et al.
The oral and skin lesions healed, and the patient was discharged from the hospital in April 2011 followed by regular controls till the end of 2011. Further medical investigation could not detect other sites of infection apart from the oral cavity and skin. The kidney biopsy was re-evaluated showing no signs H. capsulatum. The patient was HIV negative.
Discussion The first case histoplasmosis reported in Sweden was in a patient with AIDS in 1989.5 Between 1999 and 2012, eight cases have been reported at Karolinska University Laboratory, Stockholm (E. Chryssanthou, personal communication) which is the only microbiology laboratory with facilities for detection of histoplasmosis in Sweden. An European survey during 6 years in the 90s detected 118 cases. Even if that study could not determine the true incidence, histoplasmosis remains a rarely diagnosed condition in Europe.6 Histoplasmosis is primarily a pulmonary disease and most infected patients have haematogenous dissemination through parasitised macrophages. The immune system may eventually control the infection but some foci of H. capsulatum can remain viable, and reactivation of the infection can occur several years later usually after cell-
References 1. Kauffman CA. Histoplasmosis: a clinical and laboratory update. Clin Microbiol Rev 2007; 20: 115–32. 2. Torres-Rodriguez JM, SeguraRoca G, Coll J. [Histoplasmosis 45 years after infection in an immunocompetent man]. Rev Iberoam Micol 2009; 26: 244–6. 3. Salomon J, Flament Saillour M, De Truchis P, Bougnoux ME, Dromer F, Dupont B et al. An outbreak of acute pulmonary histoplasmosis in members of a trekking trip in Martinique, French West Indies. J Travel Med 2003; 10: 87–93. 4. Gascon J, Torres JM, Luburich P, Ayuso JR, Xaubet A, Corachan M. Imported histoplasmosis in Spain. J Travel Med 2000; 7: 89–91. 5. Petrini B, Gyllensten K, JorupRonstrom C, von Rosen ML. [The first case of generalized histoplasmosis in a patient with AIDS in
mediated immunosuppression1,2 and long periods of latency, up to 50 years, have been reported.2,6 As the fungus is not endemic in Sweden, the most probable source of infection of this patient was Thailand, an endemic zone for H. capsulatum, where he was on holiday in 2007 and 2008.7–9 At the initial infection, he most likely developed symptoms similar to those of influenza within the first weeks.3 The fungus remained viable and when the patient became immunosuppressed in 2010, it was reactivated.1,2,6 The patient was HIV negative, but was on corticosteroids, a therapy which is a risk factor for the disseminated form of histoplasmosis.1 Our patient severely worsened a few months after receiving corticosteroids for the previously diagnosed sarcoidosis. As there is a risk for confusion between histoplasmosis and sarcoidosis,10 re-evaluation of the kidney biopsy was performed, however, without detection of any fungi. Oral manifestations can be seen in an isolated form but are more frequently observed in the disseminated form.1,9 Disseminated histoplasmosis is a difficult diagnosis to make especially in non-endemic areas. This report can hopefully encourage clinicians from non-endemic areas to consider histoplasmosis in cases of non-remitting oral ulcers, as this disease can occur in non-HIV patients long after they have visited an endemic zone.
Sweden]. Lakartidningen 1989; 86: 4101–2. 6. Ashbee HR, Evans EG, Viviani MA, Dupont B, Chryssanthou E, Surmont I et al. Histoplasmosis in Europe: report on an epidemiological survey from the European Confederation of Medical Mycology Working Group. Med Mycol 2008; 46: 57–65. 7. Chetchotisakd P, Kiertiburanakul S, Mootsikapun P, Assanasen S, Chaiwarith R, Anunnatsiri S. Disseminated nontuberculous mycobacterial infection in patients who are not infected with HIV in Thailand. Clin Infect Dis 2007; 45: 421–7. 8. Poonwan N, Imai T, Mekha N, Yazawa K, Mikami Y, Ando A et al. Genetic analysis of Histoplasma capsulatum strains isolated from clinical specimens in Thailand by a PCRbased random amplified polymorphic DNA method. J Clin Microbiol 1998; 36: 3073–6.
9. Poinsilpa KP, Tantawichien T. Disseminated histoplasmosis in a young Thai male. J Travel Med 1994; 1: 57. 10. Walker JV, Baran D, Yakub N, Freeman RB. Histoplasmosis with hypercalcemia, renal failure, and papillary necrosis. Confusion with sarcoidosis. JAMA 1977; 237: 1350–2.
Correspondence to: Fernando J. Mota de Almeida, Department of Endodontics, Tandv ardenskompetencentrum, Skeppsbrogatan 22, Box 922, SE-971 28 Lule a, Sweden. Tel.: +46-920-71974 Fax: +46-920-71 704 E-mail: fernando.mota-de-almeida @nll.se
© 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd, Gerodontology 2015; 32: 234–236
