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Fever revealing Behçet's disease: Two new cases
European Journal of Internal Medicine 18 (2007) 146 – 147 www.elsevier.com/locate/ejim
Brief report
Fever revealing Behçet's disease: Two new cases H. Harmouche, M. Maamar ⁎, I. Sahnoune, Z. Tazi-Mezalek, M. Aouni, A. Maaouni Department of Internal Medicine Hospital Ibn Sina Rabat, Morocco Received 27 January 2006; received in revised form 15 May 2006; accepted 19 September 2006
Abstract Behçet's disease (BD) is an uncommon cause of fever of unknown origin. We report two cases, both involving 42-year-old males, who initially presented with prolonged fever and who were ultimately diagnosed as having BD after a delay of 12 and 21 months, respectively. Both patients developed pulmonary aneurysms. Although fevers resolved after therapy, both patients died within the first year after diagnosis. Clinicians should be aware that long-term fever may be an inaugural sign of BD, especially in individuals living in countries along the ancient Silk Road or Mediterranean basin. © 2007 European Federation of Internal Medicine. Published by Elsevier B.V. Keywords: Behçet's disease; Pulmonary aneurysm; Fever
1. Introduction
2. Case reports
Fever of unknown origin was first defined by Petersdof and Beeson about 45 years ago as a body temperature over 38 °C that continues for at least 3 weeks with no diagnosis being reached after 1 week of inpatient examination [1]. In recent years, Durack and Street re-defined the examination time as 3 days [2]. Behcet's disease (BD) is a multisystem inflammatory disorder of unclear etiology that is characterized by recurrent oral and genital ulcers, skin lesions such as nodular erythema, pseudofolliculitis, and uveitis. Other manifestations may include arthritis, thrombophlebitis, central nervous system disease, gastro-intestinal ulcerations, and arterial involvement. Fever may accompany bouts of the disease but has only rarely been reported as the sole manifestation preceding the other phenomena.
2.1. Case 1
⁎ Corresponding author. Tel.: +212 61 19 01 14; fax: +212 37 67 31 40, 212 37 68 20 69. E-mail address: [email protected] (M. Maamar).
A 42-year-old male was referred to our unit for prolonged fever. The patient had been well until 4 months earlier, when he began to have fever (38–39 °C). He reported a weight loss of 13 kg in 6 months. On physical examination, his blood pressure was 110/75 mmHg, pulse 96/min and regular, and temperature 38.8 °C. All of the other systems were normal and the spleen was not palpable. Skin examination showed a pseudofolliculitis. Routine laboratory examinations were normal, except for an increased sedimentation rate between 54 and 112 mm/h. Chest X-rays were normal. Tests for tuberculosis and an eye exam were normal. Serology for HIV, CMV, and hepatitis B and C were negative. Contrastenhanced computed tomography (CT) and bone marrow examination were normal. Six months later, while the patient was still suffering from fever, he developed aphtous ulcerations in the mouth with thoracic pain. On readmission, a chest X-ray showed a hilar enlargement. Chest CT scan showed bilateral pulmonary artery aneurysms. Echocardiography revealed indirect signs
0953-6205/$ - see front matter © 2007 European Federation of Internal Medicine. Published by Elsevier B.V. doi:10.1016/j.ejim.2006.09.009
H. Harmouche et al. / European Journal of Internal Medicine 18 (2007) 146–147
of myocardial infarction. Ocular exam was still normal and the sedimentation rate was increased. A pathergy test was positive. On the basis of these findings, the diagnosis of BD was made. The patient received 1 g of intravenous methylprednisolone for 3 days. He continued to take 30 mg/day of prednisone and colchicine (1 mg/day). Monthly intravenous cyclophosphamide was also administered. At first, the patient felt better, with a spectacular improvement in general signs. Yet, he died 9 months later after a diagnosis was made of a massive hemoptysis. 2.2. Case 2 A 42-year-old man was admitted to the internal medicine department with a 1-year history of fever varying from 38.5 °C to 40 °C. There was no notable illness in his past history and he had otherwise been healthy before this year. There was no significant abnormality on physical examination. Blood pressure was 140/85 mmHg, pulse 90/min and regular, and temperature between 38 and 40.8 °C. On admission, the sedimentation rate was 95 mm/h, white blood cell count 13,000/ml, and C-reactive protein 12 mg/l. All examinations (chest X-rays, abdominal echography, contrastenhanced CT, bone marrow biopsy, serology for HIV, CMV, and hepatitis B and C, blood cultures, antinuclear antibodies) were negative. The patient received antibiotics without any response. The fever responded to anti-inflammatory drugs and recurred at the withdrawal of these medications. Six months later, the patient developed abdominal pain, diarrhea, and erythema nodosum. His temperature was still high. Endoscopy of the colon showed an ulcerated ileitis without specific histological findings. Three months later, he presented with oral ulcerations and recurrent hemoptysis. A pathergy test was positive. Chest X-rays showed bilateral infiltration and a nodular opacity of the right lung. CT scan and angiography showed bilateral pulmonary aneurysms and small-vessel occlusion involving the lobar arteries. The diagnosis of BD was made. Treatment with prednisone (1 mg/kg per day), colchicine (1 mg/day), and cyclophosphamide (a monthly pulse of 1 g) was started. The pulmonary aneurysms were embolized. The patient initially improved with no more fever or hemoptysis, but he died 1 year later of septic complications (disseminated tuberculosis). 3. Discussion Our patients both fulfilled the criteria of the International Study Group for BD [3]. The exclusion of other causes of prolonged fever and the efficacy of colchicine and corticosteroids favor the causality of BD in the fever. Fever is not a specific symptom and can sometimes be associated with
147
relapses of BD. In our experience of 162 patients, 5 have presented fever occurring during a relapse of the disease [4]. This relapse has been articular, thrombophlebitic, and/or erythema nodosum. Fever can also be a sign of a complication, frequently a cardiovascular complication [4]. Our two patients had pulmonary aneurysms. Fever in BD is most often described in children and adolescents, and very few cases (fewer than 10) have been published with fever as the first symptom of the disease with a delay between the fever and the specific symptoms of BD varying from 3 months to 2 years [4]. In our patients, the typical features of BD emerged gradually, with a delay in diagnosis of 12 and 21 months. Fever is usually associated with vascular, cerebral, and cardiac involvement. The presentation of BD as a fever of unknown origin must be included in the etiologies of long-course fever, especially in the young population of Mediterranean origin. A recent Turkish study [5], in which 87 cases were evaluated over a 9year period, showed that the etiology was BD in 2 cases. The treatment of BD remains largely empirical, but new insights into its pathogenesis have led to both novel therapeutic approaches and a better understanding of the action of established treatments. The availability of new, powerful, anti-inflammatory and immunosuppressive agents, such as TNF-α blockers and interferon-α2, have provided additional tools in the treatment of recalcitrant disease [6]. 4. Learning point BD is a very rare cause of fever of unknown origin. Physicians must, however, consider this etiology, especially in individuals living in Mediterranean countries, and look for a vascular or thromboembolic complication. References [1] Petersdof RG, Beeson PB. Fever of unexplained origin: report of 100 cases. Medicine (Baltimore) 1961;40:1–30. [2] Durack DT, Street AC. Fever of unknown origin: re-examined and redefined. In: Remington JS, Swartz MN, editors. Current clinical topics in infectious diseases, 11. Boston: Blackwell Scientific Publications; 1991. p. 35–51. [3] International Study Group for Behçet's Disease. Criteria for diagnosis of Behçet's disease. Lancet 1990;335:1078. [4] Filali-Ansary N, Tazi Mezalek Z, Mohattane A, Adnaoui M, Maaouni A, Berbich A. La maladie de Behçet, A propos de 162 observations. Ann Méd Interne 1999;150:178–8. [5] Saltoglu N, Tasova Y, Midikli D, Aksu HSZ, Sanli A, Dündar IH. Fever of unknown origin in Turkey: evaluation of 87 cases during a nine-yearperiod of study. J Inf 2004;48:81–5. [6] Pipitone N, Olivieri I, Cantini F, Triolo G, Salvarani C. New approaches in the treatment of Adamantiades–Behcet's disease. Curr Opin Rheumatol 2006;18:3–9.
Brief report
Fever revealing Behçet's disease: Two new cases H. Harmouche, M. Maamar ⁎, I. Sahnoune, Z. Tazi-Mezalek, M. Aouni, A. Maaouni Department of Internal Medicine Hospital Ibn Sina Rabat, Morocco Received 27 January 2006; received in revised form 15 May 2006; accepted 19 September 2006
Abstract Behçet's disease (BD) is an uncommon cause of fever of unknown origin. We report two cases, both involving 42-year-old males, who initially presented with prolonged fever and who were ultimately diagnosed as having BD after a delay of 12 and 21 months, respectively. Both patients developed pulmonary aneurysms. Although fevers resolved after therapy, both patients died within the first year after diagnosis. Clinicians should be aware that long-term fever may be an inaugural sign of BD, especially in individuals living in countries along the ancient Silk Road or Mediterranean basin. © 2007 European Federation of Internal Medicine. Published by Elsevier B.V. Keywords: Behçet's disease; Pulmonary aneurysm; Fever
1. Introduction
2. Case reports
Fever of unknown origin was first defined by Petersdof and Beeson about 45 years ago as a body temperature over 38 °C that continues for at least 3 weeks with no diagnosis being reached after 1 week of inpatient examination [1]. In recent years, Durack and Street re-defined the examination time as 3 days [2]. Behcet's disease (BD) is a multisystem inflammatory disorder of unclear etiology that is characterized by recurrent oral and genital ulcers, skin lesions such as nodular erythema, pseudofolliculitis, and uveitis. Other manifestations may include arthritis, thrombophlebitis, central nervous system disease, gastro-intestinal ulcerations, and arterial involvement. Fever may accompany bouts of the disease but has only rarely been reported as the sole manifestation preceding the other phenomena.
2.1. Case 1
⁎ Corresponding author. Tel.: +212 61 19 01 14; fax: +212 37 67 31 40, 212 37 68 20 69. E-mail address: [email protected] (M. Maamar).
A 42-year-old male was referred to our unit for prolonged fever. The patient had been well until 4 months earlier, when he began to have fever (38–39 °C). He reported a weight loss of 13 kg in 6 months. On physical examination, his blood pressure was 110/75 mmHg, pulse 96/min and regular, and temperature 38.8 °C. All of the other systems were normal and the spleen was not palpable. Skin examination showed a pseudofolliculitis. Routine laboratory examinations were normal, except for an increased sedimentation rate between 54 and 112 mm/h. Chest X-rays were normal. Tests for tuberculosis and an eye exam were normal. Serology for HIV, CMV, and hepatitis B and C were negative. Contrastenhanced computed tomography (CT) and bone marrow examination were normal. Six months later, while the patient was still suffering from fever, he developed aphtous ulcerations in the mouth with thoracic pain. On readmission, a chest X-ray showed a hilar enlargement. Chest CT scan showed bilateral pulmonary artery aneurysms. Echocardiography revealed indirect signs
0953-6205/$ - see front matter © 2007 European Federation of Internal Medicine. Published by Elsevier B.V. doi:10.1016/j.ejim.2006.09.009
H. Harmouche et al. / European Journal of Internal Medicine 18 (2007) 146–147
of myocardial infarction. Ocular exam was still normal and the sedimentation rate was increased. A pathergy test was positive. On the basis of these findings, the diagnosis of BD was made. The patient received 1 g of intravenous methylprednisolone for 3 days. He continued to take 30 mg/day of prednisone and colchicine (1 mg/day). Monthly intravenous cyclophosphamide was also administered. At first, the patient felt better, with a spectacular improvement in general signs. Yet, he died 9 months later after a diagnosis was made of a massive hemoptysis. 2.2. Case 2 A 42-year-old man was admitted to the internal medicine department with a 1-year history of fever varying from 38.5 °C to 40 °C. There was no notable illness in his past history and he had otherwise been healthy before this year. There was no significant abnormality on physical examination. Blood pressure was 140/85 mmHg, pulse 90/min and regular, and temperature between 38 and 40.8 °C. On admission, the sedimentation rate was 95 mm/h, white blood cell count 13,000/ml, and C-reactive protein 12 mg/l. All examinations (chest X-rays, abdominal echography, contrastenhanced CT, bone marrow biopsy, serology for HIV, CMV, and hepatitis B and C, blood cultures, antinuclear antibodies) were negative. The patient received antibiotics without any response. The fever responded to anti-inflammatory drugs and recurred at the withdrawal of these medications. Six months later, the patient developed abdominal pain, diarrhea, and erythema nodosum. His temperature was still high. Endoscopy of the colon showed an ulcerated ileitis without specific histological findings. Three months later, he presented with oral ulcerations and recurrent hemoptysis. A pathergy test was positive. Chest X-rays showed bilateral infiltration and a nodular opacity of the right lung. CT scan and angiography showed bilateral pulmonary aneurysms and small-vessel occlusion involving the lobar arteries. The diagnosis of BD was made. Treatment with prednisone (1 mg/kg per day), colchicine (1 mg/day), and cyclophosphamide (a monthly pulse of 1 g) was started. The pulmonary aneurysms were embolized. The patient initially improved with no more fever or hemoptysis, but he died 1 year later of septic complications (disseminated tuberculosis). 3. Discussion Our patients both fulfilled the criteria of the International Study Group for BD [3]. The exclusion of other causes of prolonged fever and the efficacy of colchicine and corticosteroids favor the causality of BD in the fever. Fever is not a specific symptom and can sometimes be associated with
147
relapses of BD. In our experience of 162 patients, 5 have presented fever occurring during a relapse of the disease [4]. This relapse has been articular, thrombophlebitic, and/or erythema nodosum. Fever can also be a sign of a complication, frequently a cardiovascular complication [4]. Our two patients had pulmonary aneurysms. Fever in BD is most often described in children and adolescents, and very few cases (fewer than 10) have been published with fever as the first symptom of the disease with a delay between the fever and the specific symptoms of BD varying from 3 months to 2 years [4]. In our patients, the typical features of BD emerged gradually, with a delay in diagnosis of 12 and 21 months. Fever is usually associated with vascular, cerebral, and cardiac involvement. The presentation of BD as a fever of unknown origin must be included in the etiologies of long-course fever, especially in the young population of Mediterranean origin. A recent Turkish study [5], in which 87 cases were evaluated over a 9year period, showed that the etiology was BD in 2 cases. The treatment of BD remains largely empirical, but new insights into its pathogenesis have led to both novel therapeutic approaches and a better understanding of the action of established treatments. The availability of new, powerful, anti-inflammatory and immunosuppressive agents, such as TNF-α blockers and interferon-α2, have provided additional tools in the treatment of recalcitrant disease [6]. 4. Learning point BD is a very rare cause of fever of unknown origin. Physicians must, however, consider this etiology, especially in individuals living in Mediterranean countries, and look for a vascular or thromboembolic complication. References [1] Petersdof RG, Beeson PB. Fever of unexplained origin: report of 100 cases. Medicine (Baltimore) 1961;40:1–30. [2] Durack DT, Street AC. Fever of unknown origin: re-examined and redefined. In: Remington JS, Swartz MN, editors. Current clinical topics in infectious diseases, 11. Boston: Blackwell Scientific Publications; 1991. p. 35–51. [3] International Study Group for Behçet's Disease. Criteria for diagnosis of Behçet's disease. Lancet 1990;335:1078. [4] Filali-Ansary N, Tazi Mezalek Z, Mohattane A, Adnaoui M, Maaouni A, Berbich A. La maladie de Behçet, A propos de 162 observations. Ann Méd Interne 1999;150:178–8. [5] Saltoglu N, Tasova Y, Midikli D, Aksu HSZ, Sanli A, Dündar IH. Fever of unknown origin in Turkey: evaluation of 87 cases during a nine-yearperiod of study. J Inf 2004;48:81–5. [6] Pipitone N, Olivieri I, Cantini F, Triolo G, Salvarani C. New approaches in the treatment of Adamantiades–Behcet's disease. Curr Opin Rheumatol 2006;18:3–9.