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A Thesis Submitted in Partial Fulfillment for the Requirements of the Degree of Clinical MD in Medicine, April, 2004

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A Thesis Submitted in Partial Fulfillment for the Requirements of the Degree of Clinical MD in Medicine, April, 2004 UNIVERSITY OF KHARTOUM Faculty of Medicine Postgraduate Medical Studies Board PATTERNS OF EXTRA-PULMONARY TUBERCULOSIS IN ADULT SUDANESE PATIENTS By Dr. Mohammed Osman Ahmed Minni M.B.B.S (University of Kassala) A thesis Submitted in partial fulfillment for the requirements of the Degree of Clinical MD in Medicine, April, 2004 Supervisor Prof. Abdel Gadir Mohammed Yousif Al kadaru FRCP-PhD, London 1 ﻗﺎل اﷲ ﺗﻌﺎﻟﻰ : (وﻗﻞ رﺑﻲ زدﻧﻲ ﻋ ﻠ ﻤ ﺎً) ﺻﺪق اﷲ اﻟﻌﻈﻴﻢ 2 To my parents 3 I would like to express my sincere thanks and gratitude to my supervisor Prof. Abdel Gadir Mohammed Yousif Alkadaru, Dean of Faculty of Medicine University of Khartoum, for his meticulous supervision, continuous guidance, encouragement and for his very valuable advice throughout all stages of the study. Also I would like to record my heart full thanks to my colleagues Dr. Rashida, Dr. Amani, Dr. Tahani and Dr. Amal who helped me in data collection. Sincere thanks to my colleague Dr. Marwa Ismail who supplied me with some of the literature. I am also grateful for Mr. Hassan Ali for data analysis and Miss Widad A/Magsood for typing the thesis. 4 ABBREVIATIONS Abbreviation Meaning 99TC-MDP 99Technitium-methylene diphosphonate AD Adenosine deaminase ARI Average risk of infection BC Before christ BCG Bacillus Calmette Guerin C.T Computed Tomography CNS Central nervous system CSF Cerebrospinal fluid CXR Chest X-ray DOTs Directly observed treatments ECG Electrocardiogram EEG Electroencephalogram 5 ESR Erythrocyte sedimentation rate EX. Pul-TB Extra-pulmonary tuberculosis FMOH Federal Ministry of Health FNA Fine needle aspiration GIT Gastrointestinal tract HIV Human immunodefiency virus IFN Interferon INH Isoniazid IUAT-LD International Union Against Tuberculosis and Lung Disease MTB Mycobaecterium tuberculosis NTP National Tuberculosis Program PCR Polymerase chain reaction PDD Purified protein derivitives PZH Pyrazinamid S1 Sacroiliac joint TB Tuberculosis US Ultrasound WHO World Health Organization 6 ABSTRACT Tuberculosis is found worldwide, but it is particularly common in Africa and Asia. The prevalence of tuberculosis increases with poor social conditions, inadequate nutrition and over crowding. The impact of tuberculosis in the developing world has been magnified in the past 20 years by the emergence of HIV pandemic(10). This study is carried out as trial to evaluate the clinical presentations of extra pulmonary tuberculosis, to 7 assess methods used in the diagnosis, and to identify factors that may predispose to the disease. In this study 100 patients of different types of extra-pulmonary TB were enrolled. Abdominal TB was found to be the commonest (37%), followed by tuberculous lymphadenitis (20%). TB of the skeleton and that of the pleura accounted to (19%) and (9%) respectively, while CNS TB was found in (4%) of the study. Genitourinary, pericardial and miliary TB each was observed in (3%) of the cases. Cutaneous TB was the least encountered, occurring in only 2 of the 100 patients. Clinical manifestations generally depend on the organ involved in addition to the general symptoms such as fever, weight loss and night sweat. Ascites was the commonest presentation of abdominal TB whereas enlarged lymph nodes with or without sinus formation were the commonest presentation of tuberculous lymphadenitis. 8 Affection of the dorsal spine with or without kyphos formation was the remarkable feature of spinal TB. Pleural tuberculosis presented mainly with unilateral pleural effusion. Signs of space occupying lesion were the main mode of presentation of CNS tuberculosis as well as tuberculous meningitis. Pericardial tuberculosis presented with effusion in two patients while in one patient it presented with constrictive pericarditis. In most patients the diagnosis was made on clinical grounds in addition to the presence of a high ESR and a positive Mantoux test as well as other specific investigations such as ascitic, pleural, pericardial and cerebrospinal fluids analysis. Tissue histopathology was obtained in a minority of patients (38%) and in all of them it showed the specific features of tuberculosis. Most patients did not receive BCG vaccination. HIV screening test was done for 56 patients and it was positive in 18 of them. Pulmonary tuberculosis can co-exist although not commonly with extra-pulmonary TB and in fact 9 sputum for acid alcohol fast bacilli was positive in 4 of the enrolled cases. 10 ﻤﻠﺨﺹ ﺍﻷﻁﺭﻭﺤﺔ ﺍﻟﺩﺭﻥ ﻤﻥ ﺍﻷﻤﺭﺍﺽ ﺍﻟﺸﺎﺌﻌﺔ ﻓﻲ ﻜل ﺍﻟﻌﺎﻟﻡ ﻭﺨﺎﺼﺔ ﺇﻓﺭﻴﻘﻴﺎ ﻭﺁﺴﻴﺎ . ﻨـﺴﺒﺔ ﺍﻹﺼـﺎﺒﺔ ﺒﺎﻟﺩﺭﻥ ﺘﺯﺩﺍﺩ ﻓﻲ ﺍﻟﻤﺠﺘﻤﻌﺎﺕ ﺍﻟﻔﻘﻴﺭﺓ ﺤﻴﺙ ﺍﻟﺘﻐﺫﻴﺔ ﺍﻟﻀﻌﻴﻔﺔ ﻭﺍﻻﺯﺩﺤﺎﻡ. ﻜﻤﺎ ﻫﻭ ﻤﻌﻠﻭﻡ ﺃﻥ ﺃﺜﺭ ﺍﻟﺘﺩﺭﻥ ﻓﻲ ﺍﻟﻌﺎﻟﻡ ﻋ ﻤ ﻭ ﻤ ﺎﹰ ﻭﺍﻟﺜﺎﻟﺙ ﻤﻨﻪ ﺨﺎﺼـﺔ ﺘﻨـﺎﻤﻰ ﺨـﻼل ﺍﻟﻌﺸﺭﻴﻥ ﺴﻨﺔ ﺍﻟﻤﺎﻀﻴﺔ ﻨﺴﺒﺔ ﻟﺘﻔﺸﻲ ﻤﺭﺽ ﻨﻘﺹ ﺍﻟﻤﻨﺎﻋﺔ ﺍﻟﻤﻜﺘﺴﺒﺔ. ﺃﺠﺭﻴﺕ ﻫﺫﻩ ﺍﻟﺩﺭﺍﺴﺔ ﻜﻤﺤﺎﻭﻟﺔ ﻟﺘﻘﻴﻴﻡ ﺍﻟﺼﻭﺭ ﺍﻟﺴﺭﻴﺭﻴﺔ ﺍﻟﻤﺨﺘﻠﻔﺔ ﻟﻠﺴل ﺨﺎﺭﺝ ﺍﻟﺭﺌﺔ ، ﻁﺭﻕ ﺍﻟﺘﺸﺨﻴﺹ ﺍﻟﻤﺘﺒﻌﺔ ﻭ ﻤﺤﺎﻭﻟﺔ ﻤﻌﺭﻓﺔ ﺍﻟﻌﻭﺍﻤل ﺍﻟﻤﺅﻫﺒﺔ ﻟﻺﺼﺎﺒﺔ ﺒﺎﻟﻤﺭﺽ. ﻫﺫﻩ ﺍﻟﺩﺭﺍﺴﺔ ﺍﻟﺘﻲ ﺸﻤﻠﺕ 100 ﻤﺭﻴﺽ ﺃﻭﻀﺤﺕ ﺃﻥ ﺍﻟﺴل ﺍﻟﺒﻁﻨﻲ ﻫﻭ ﺃﻜﺜﺭ ﺍﻷﻨـﻭ ﺍﻉ ﺸ ﻴ ﻭ ﻋ ﺎﹰ ﺤﻴﺙ ﻜﺎﻨﺕ ﻨﺴﺒﺔ ﺍﻹﺼﺎﺒﺔ ﺒﻪ 37% ﻴﻠﻴﻪ ﺴل ﺍﻟﻐﺩﺩ ﺍﻟﻠﻴﻤﻔﺎﻭﻴﺔ ﻭﻜﺎﻨﺕ ﺍﻹﺼﺎﺒﺔ ﺒﻪ %20، ﺜﻡ ﺍﻟﺴل ﺍﻟﻌﻅﻤﻲ 19% ، ﺍﻟﺴل ﺍﻟﺒﻠﻭﺭﻱ 9%. ﺇﺼﺎﺒﺔ ﺍﻟﺠﻬﺎﺯ ﺍﻟﻌﺼﺒﻲ ﺍﻟﻤﺭﻜﺯﻱ ﺒﺎﻟﺴل ﻭﺠﺩﺕ ﻓﻲ 4% ﻤﻥ ﺍﻟﺤﺎﻻﺕ ﺒﻴﻨﻤﺎ ﺇﺼﺎﺒﺔ ﺍﻟﺠﻬﺎﺯ ﺍﻟﺒﻭﻟﻲ ﺍﻟﺘﻨﺎﺴﻠﻲ ، ﺍﻟـﺴل ﺍﻟـﺩﺨﻨﻲ ﻭﻏـﺸﺎﺀ ﺍﻟﻘﻠـﺏ ﺍﻟﺘﺎﻤﻭﺭﻱ ﻭﺠﺩﺕ ﻓ ﻲ 3% ، ﺃﻤﺎ ﺍﻟﺴل ﺍﻟﺠﻠﺩﻱ ﻓﻬﻭ ﺃﻗل ﺍﻷﻨﻭﺍﻉ ﺸ ﻴ ﻭ ﻋ ﺎﹰ ﺤﻴﺙ ﻭﺠﺩ ﻓﻲ ﻤﺭﻴﻀﻴﻥ ﻓﻘﻁ. ﻤﻥ ﺨﻼل ﺍﻟﺩﺭﺍﺴﺔ ﻨﻼﺤﻅ ﺃﻥ ﺍﻷﻋﺭﺍﺽ ﺍﻟﺴﺭﻴﺭﻴﺔ ﺘﻌﺘﻤﺩ ﻋﻠـﻰ ﺍﻟﻌـﻀﻭ ﺍﻟﻤـﺼﺎﺏ ﺒﺎﻹﻀﺎﻓﺔ ﻟﺒﻌﺽ ﺍﻷﻋﺭﺍﺽ ﺍﻟﻌﺎﻤﺔ ﻤﺜل ﺍﻟﺤﻤﻰ ، ﺍﻟﺘﻌﺭﻕ ﺍﻟﻠﻴﻠﻲ ﻭ ﻨﻘﺹ ﺍﻟﻭﺯﻥ . ﺇﻟﺘﻬﺎﺏ ﺍﻟﻐـﺸﺎﺀ ﺍﻟﺒﺭﻴﺘﻭﻨﻲ ﻭﺘﺠﻤﻊ ﺴﺎﺌل ﺩﺍﺨل ﺍﻟﻐﺸﺎﺀ ﺍﻟﺒﺭﻴﺘﻭ ﻨﻲ (ﺍﺴﺘﺴﻘﺎﺀ) ﻫﻲ ﺍﻟﺼﻭﺭﺓ ﺍﻟﺴﺭﻴﺭﻴﺔ ﺍﻷﻜﺜﺭ ﺸ ﻴ ﻭ ﻋ ﺎﹰ ﻟﻠﺴل ﺍﻟﺒﻁﻨﻲ ﺒﻴﻨﻤﺎ ﺘﻀﺨﻡ ﺍﻟﻐﺩﺩ ﺍﻟﻠﻴﻤﻔﺎﻭﻴﺔ ﻤﻊ ﺤﺩﻭﺙ ﺃﻭ ﻋﺩﻡ ﺤﺩﻭﺙ ﺘﻘﺭﺤﺎﺕ ﺒﻬﺎ ﻫﻲ ﺍﻟﺼﻭﺭﺓ ﺍﻟﺴﺭﻴﺭﻴﺔ ﺍﻟﺸﺎﺌﻌﺔ ﻟﺴل ﺍﻟﻐﺩﺩ ﺍﻟﻠﻴﻤﻔﺎﻭﻴﺔ. 11 ﺍﻟﻌﻤﻭﺩ ﺍﻟﻔﻘﺭﻱ ﺍﻟﻅﻬﺭﻱ ﻫﻭ ﺃﻜﺜﺭ ﺍﻟﻔﻘﺭﺍﺕ ﺇﺼﺎﺒﺔ . ﺃﻟﻡ ﺍﻟﻅﻬﺭ ﻤﻊ ﺍﺤﺘﻤﺎل ﺤـﺩﻭﺙ ﺃﻭ ﻋﺩﻡ ﺤﺩﻭﺙ ﺇﻋﻭﺠﺎﺝ ﻓﻲ ﺍﻟﻌﻤﻭﺩ ﺍﻟﻔﻘﺭﻱ ﺍﻟﻅﻬﺭﻱ ﺘﻤﺜﻼﻥ ﺍﻟﺼﻭﺭﺓ ﺍﻟﺴﺭﻴﺭﻴﺔ ﺍﻟﺭﺌﻴﺴﻴﺔ ﻟﻺﺼـﺎﺒﺔ ﺒﺎﻟﺴل ﺍﻟﻌﻅﻤﻲ. ﺍﻟﺴل ﺍﻟﺒﻠﻭﺭﻱ ﺘﺘﻤﺜل ﺃﻋﺭﺍﻀﻪ ﻓﻲ ﺘﻜﻭﻥ ﻭﺘﺠﻤﻊ ﺴﺎﺌل ﺩﺍﺨل ﺍﻟﻐﺸﺎﺀ ﺍﻟﺒﻠﻭﺭﻱ. ﺇﺭﺘﻔﺎﻉ ﻀﻐﻁ ﺍﻟﺭﺃﺱ ﺒﺎﻹﻀﺎﻓﺔ ﻻﻟﺘﻬﺎﺏ ﺍﻟﺴﺤﺎﺌﻲ ﺍﻟﺩﺭﻨﻲ ﺘﻤﺜﻼﻥ ﺍﻟﺼﻭﺭﺓ ﺍﻟـﺴﺭﻴﺭﻴﺔ ﻟﺴل ﺍﻟﺠﻬﺎﺯ ﺍﻟﻌﺼﺒﻲ ﺍﻟﻤﺭﻜﺯﻱ ، ﺃ ﻴ ﻀ ﺎﹰ ﺃﻭﻀﺤﺕ ﺍﻟ ﺩﺭﺍﺴﺔ ﺃﻥ ﺍﻟﺘﻬﺎﺏ ﺍﻟﻐﺸﺎﺀ ﺍﻟﺘـﺎﻤﻭﺭﻱ ﻟﻠﻘﻠـﺏ ﻭﺘﺠﻤﻊ ﺴﺎﺌل ﺩﺍﺨل ﺍﻟﻐﺸﺎﺀ ﺍﻟﺘﺎﻤﻭﺭﻱ ﻫﻲ ﺍﻟﺼﻭﺭﺓ ﺍﻟﺴﺭﻴﺭﻴﺔ ﺍﻟﺭﺌﻴﺴﻴﺔ ﻹﺼﺎﺒﺔ ﺍﻟﻘﻠﺏ ﺒﺎﻟﺴل. ﻓﻲ ﻜل ﻫﺫﻩ ﺍﻷﻨﻭﺍﻉ ﺍﻋﺘﻤﺩ ﺍﻟﺘﺸﺨﻴﺹ ﻋﻠﻰ ﺍﻟﺤﺎﻟﺔ ﺍﻟﺴﺭﻴﺭﻴﺔ ﻭ ﺇﺭﺘﻔﺎﻉ ﺘﺭﺴـﺏ ﺍﻟـﺩﻡ ﻭﺇﻴﺠﺎﺒﻴﺔ ﺍﻟﻔﺤﺹ ﺍﻟﻤﻨﺎﻋﻲ (ﺍﻟﻤﺎﻨﺘﻭ) ﺇﻀﺎﻓﺔ ﺇﻟﻰ ﺒﻌﺽ ﺍﻟﻔﺤﻭﺼﺎﺕ ﺍﻟﺨﺎﺼﺔ ﻤﺜل ﺘﺤﻠﻴل ﺍﻟـﺴﺎﺌل ﺍﻟﺒﺭﻴﺘﻭﻨﻲ ، ﺴﺎﺌل ﺍﻟﺒﻠﻭﺭﺓ ، ﺴﺎﺌل ﺍﻟﺘﺎﻤﻭﺭ ، ﻭﺍﻟﺴﺎﺌل ﺍﻟﻅﻬـﺭﻱ . ﺍﻟﺨـﺯﻉ ﺍﻟﻨـﺴﻴﺠﻴﺔ ﻜﻭﺴـﻴﻠﺔ ﻟﻠﺘﺸﺨﻴﺹ ﺍﻋﺘﻤﺩﺕ ﻓﻲ 37 ﻤﺭﻴﺽ ﻓﻘﻁ. ﻤﻌﻅﻡ ﺍﻟﻤﺭﻀﻰ ﻟﻡ ﻴﻁﻌﻤﻭﺍ ﻀﺩ ﺍﻟﺴل ﻤﻥ ﻗﺒل . ﻓﺤﺹ ﺍﻹﻴﺩﺯ ﺃﺠﺭﻱ ﻓﻲ 38 ﻤﺭﻴﺽ ﻭﻜﺎﻨﺕ ﺍﻟﻨﺘﻴﺠﺔ ﺇﻴﺠﺎﺒﻴﺔ ﻓﻲ 18 ﻤﺭﻴﺽ ، ﺍﻹﺼﺎﺒﺔ ﺍﻟﻤﺘﺯﺍﻤﻨﺔ ﺒﺎﻟﺴل ﺍﻟﺭﺌﻭﻱ ﻏﻴﺭ ﺸـﺎﺌﻌﺔ ﺤﻴـﺙ ﻭﺠﺩﺕ ﻓﻲ ﺃﺭﺒﻊ ﻤﺭﻀﻰ ﻓﻘﻁ. 12 LIST OF FIGURES Page Figure 1: Frequency of the different types of extra- pulmonary tuberculosis 66 Figure 2: Symptoms and signs in abdominal tuberculosis 67 Figure 3: Investigations used in the diagnosis of abdominal tuberculosis 68 Figure 4: Lymph node group involvement in lymph node tuberculosis 69 Figure 5: Symptoms and signs in patients with spinal tuberculosis 70 Figure 6: Sites of lesions according to the clinical and MRI findings 71 Figure 7: X-ray findings in pleural effusion 72 Figure 8: Investigations used in the diagnosis of pleural tuberculosis 73 Figure 9: Investigations used in the dignosis of CNS 13 tuberculosis 74 Figure 10: Symptoms and signs in patients with heart tuberculosis 75 Figure 11: Investigations used in the diagnosis of heart tuberculosis 76 14 LIST OF TABLES Page Table 1: Frequency of general symptoms in each type of extra- pulmonary tuberculosis 60 Table 2: Risk factors in each type of extra-pulmonary tuberculosis 61 Table 3: HIV status in different types of extra pulmonary tuberculosis 62 Table 4: General investigations different types of the extra- pulmonary tuberculosis 63 Table 5: Distribution of gender in the different types of the extra- pulmonary tuberculosis in the study 64 Table 6: Distribution of age in the different types of extra-pulmonary tuberculosis in the study 65 15 CONTENTS Page Dedication …………………………………………………………..…...I Acknowledgment………………………………………………………..I I Abbreviations………………………………………………………...…II I English abstract………………………………………………………..V Arabic abstract……………………………………...……… …….…..VII List of tables…………………………………………………….……...X List of figures ……………………………………...………………..…IX CHAPTER ONE INTRODUCTION AND LITERATURE REVIEW…….. ……………1 OBJECTIVES………………………………………………………...47 CHAPTER TWO PATIENTS & METHODS …………………………………………...48 CHAPTER THREE RESULTS …………………………………………………………….50 16 CHAPTER FOUR DISCUSSION……………………………………………………….…76 CONCLUSION …………………………………………………….….85 RECOMMENDATIONS ………………………………………….…..87 REFERENCES………………………………………………………..88 APPENDIX : Questionnaire 17 18 INTRODUCTION 1.1. Definition Tuberculosis is a communicable systemic disease caused by the tubercle bacillus, “mycobacterium tuberculosis”. Most infections are caused by inhalation of droplet nuclei containing virulent human strains of the tubercle bacillus. Infection by mycobacterium bovis through ingestion of unpausterlized cow’s milk is less common. Almost every organ in the body can be affected but involvement of the lungs accounts for more than 80% of tuberculosis cases. (1) 1.2. Brief history of Tuberculosis Mycobacterium tuberculosis has been present in the human population since before christ as antiquity- fragments of the spinal column from Egyptian mummies 2400 before christ (BC) show definite pathological signs of tubercular decay. Exact pathological and anatomical descriptions of the disease began to appear in the seventeenth century. In his Opera Medica of 1697, Sylvius was the first to identify that actual tubercles are consistent and characteristic changes in the lungs and other areas of consumptive
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