Tosaddak Ahmed MBBS (Calcutta), DTM & H (Eng), FRCP (Lond)
Consultant General andd Chest Physician King Fahad Hospital
Madinah Al-Munawara Kingdom of Saudi Arabia
7To
9Preface
Jitendar P Vij
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Difficult Diagnosis and Management of Tuberculosis Made Easy®
© 2010, Tosaddak Ahmed
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First Edition: 2010
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“Verily, God and His angels shower blessings on the Prophet. O ye who believe! ask blessings on him and salute him with a worthy salutation.”
In-depth studies into the 65 cases of tuberculosis involving pulmonary as well as extra-pulmonary sites, in almost all the organ systems of the body, will lead the students and the doctors into the disease processes in any system, and its understanding. It will be like “Know of tuberculosis, and you will know about all other diseases of the body”.
As these cases were not of the common and usual form of pulmonary tuberculosis, its management could not follow a rigid protocol as it is normally employed in those circumstances. It is flexible, liberal and individualised on each patient's disease status and demands; without compromising on the safety and efficacy of the anti-tuberculosis drugs given in the best of the ways. This will help doctors to adapt such approach that is rational, safe and satisfactory in the management of tuberculosis.
Tuberculosis, as it is commonly encountered, is a simple and straight-forward disease in its presentation and diagnosis; and not very appealing intellectually to the doctors. This notion might be shaken, hopefully, by these case reports, and it would help attracting the attention of more professionally competent physicians of tuberculosis. This will be important in getting newer potent antitubercular drugs and more effective vaccines which are needed now even more than ever before, with increasing multi-drug resistant and extensively-drug resistant tuberculosis in the background; and persistance of this disease of antiquity as a source of continuing threat, distress and suffering to the people worldwide.
11Acknowledgements
I would like to thank my colleagues whose names are mentioned below for referring their cases to our unit and for their opinions; and staff of chest medical unit and other personnel at King Fahad Hospital who were involved in the care of these patients; and particularly Dr Ayman Iskandrani for his cooperation and encouragement.
- Dr Abdullah Reda Allam mbbs, frcs (lond), Consultant Cardiothoracic Surgeon and Chief of the Department of Cardiothoracic Surgery.
- Dr Ayman Mohamed Iskandrani md, Consultant Chest Physician and Chief of the Department of Chest Medicine.
- Dr Dardiri Abdullah mbbs, frcs (edin), Consultant General Surgeon.
- Dr Jamil Ahmed md, frcr (lond), Consultant Radiologist.
- Dr Mosleh Al Raddadi md, Consultant Radiologist and Chief of the Department of Radiology.
- Dr Osama Al Amoudi md, Consultant Cardiologist and Chief of the Department of Cardiology.
- Dr Yousuf Akkaya md, Consultant Neurosurgeon, Department of Neurosurgery.
All of the above are the staff at King Fahad Hospital, Madinah Al-Munawara, Kingdom of Saudi Arabia. My thanks to Mr Sheikh Irfan for taking and processing the photographs of X-rays and MRI images.
I am ever indebted to my family for their support, specially to my wife for her endurance and hardship during the period of preparation of the manuscript; and to Dr Alijah Ahmed, Dr Arif Ahmed, Dr Tasneem Ahmed and Dr Amer Ahmed, for their assistance in its preparation.
13Introduction
Tuberculosis (TB) is still a growing health problem worldwide, mostly in the poor and developing countries. Worldwide, more than 3 million people die and 8 million new cases occur from this disease every year, of these 74% are in Asia and 12% in Africa.1, 2 Nearly four decades ago, with the advent of potent antitubercular drugs, it was thought that TB would no longer be a threat to mankind. It was even thought that TB would soon become one of those rare infective diseases. TB is intimately linked with social ills such as poverty,3 malnutrition,4 state of famine and warfare; and as these factors cannot ever be eliminated, TB will be with us. Moreover, there are other factors that will ensure that TB remains active in the community. These include the increasing incidence of breakdown of immunological strength, either through diseases such as HIV infection and AIDS (of which 30 to 50% have concomitant TB, in poor countries),5, 6 malignancy, or resulting from the treatment of immune disorder diseases, and the prevention of transplant rejection.
Even when TB is considered to be a global health problem of serious nature, and was declared by World Health Organization a health emergency in 1996, the effort in finding more potent antitubercular agents and vaccines, and containing emergence of resistant strain Mycobacteria,7, 8 remains in low intensity and rather half hearted. This is largely due to the fact that the medical profession in poor and developing countries, which receive the brunt of the disease, is not capable or, for some reason, motivated to take action to that effect. TB does not attract the attention of the doctors in developed countries as their encounter with the disease is infrequent, and its mundane presentation with cough, sputum, nocturnal fever and sweating, loss of appetite and weight, apical infiltration in chest X-ray and sputum positive for AFB, is not very appealing to them intellectually.
Accounts of these cases of TB with unusual presentation may hopefully, to some extent, succeed in creating interest and drawing attention of the doctors towards this disease of antiquity and ever present menace towards mankind.
Almost all of these patients were seen and treated as inpatients and outpatients at King Fahad District General Hospital at Madinah Al-Munawara, Saudi Arabia. Most of the patients were seen in between 2000 and 2004. Patients suffering from similar nature of TB prior to this period, except few, were not included because of inadequate information that could be obtained from the records of those patients, and also to limit the volume of this presentation.
Most of these patients were of Saudi nationality, but some belonged to other nationalities, as city of Medina has enclaves where people from other countries resides as communities; and a large number of expatriate workers.
Antitubercular drugs regimens and administration followed the usual protocols and schedules. Dosages of the drugs used were as follows: (see on next page)9, 10
| :300 mg OD (10 mg/kg). |
| :450 mg OD (BW < 50 kg). |
600 mg OD (BW ≥ 50 kg) (10-20 mg/kg). | |
| :25 mg/kg - for 2 months, then 15 mg/kg if continued beyond 2 months. |
| :1.5 gm OD (BW < 50 kg). |
2 gm OD (BW ≥ 50 kg) (40 mg/kg). | |
| :750 mg IM OD (BW < 50 kg). |
1 g IM OD (BW ≥ 50 kg, age < 40 years) (40 mg/kg). | |
Dose of 1 gm IM on alternate days was commonly used. | |
| :1000-1500 mg tablet OD. |
| :400 mg tablet/IV OD. |
| :400 mg tablet/IV OD. |
TABLE: ANTITUBERCULOUS DRUGS, THEIR DOSAGE AND TOXICITY
Drug and route of administration | Body weight | Daily therapy dose | Intermittent therapy dose | Daily dose for children | Toxicity |
Isoniazid oral IM | 300 mg | 15 mg/kg | 10 mg/kg | Hepatitis, peripheral neuropathy, CNS effects, hypersensitivity | |
Rifampicin oral | < 50 kg | 450 mg | 600-900 mg | 10-20 mg/kg | Fever, thrombocytopenia, rash, hepatitis |
Streptomycin im | ≥50 kg<50 kg | 600 mg 750 mg | 600-900 mg 750 mg | 20 mg/kg | Ototoxicity; nephrotoxicity, fever |
pyrazinamide oral | ≥ 50 kg <50 kg | 1 gm (age < 40)1.5 gm | 3 times/wk 2 gm | 40 mg/kg | Hyperuricaemia, hepatitis, rash, photosensitivity |
≥50 kg | 2 gm | twice wkly 3 gm 3 times wkly 2.5 gm twice wkly 3.5 gm | |||
Ethambutol oral | 25 mg/kg-for 2 months; then 15 mg/kg | 3 times wkly-30 mg/kg, twice wkly 45 mg/kg | Optic neuritis, central scotoma, loss of red-green perception | ||
PAS oral | 10-15 gm (two divided doses) | 300 mg/kg | Gastrointestinal, hepatitis, rash, goitre | ||
Ethionamide oral | 500-750 mg | 10-15 mg/kg | Gastrointestinal, hepatitis, goitre, neuropathy | ||
cycloserine oral | 750-1000 mg | 15 mg/kg | Psychosis, rash, convulsion | ||
thiacetazone oral | 150 mg | 4 mg/kg | Gastrointestinal, vestibular | ||
kanamycin IM | 0.5 gm | 1 gm 3 times/wk | Ototoxicity, nephrotoxicity | ||
capreomycin IM | 1 gm | 15 mg/kg | Ototoxicity, nephrotoxicity | ||
viomycin IM | 0.5 gm | 1 gm 3 times/wk | Ototoxicity, nephrotoxicity |
Where second-line antitubercular drugs were required, which was very rare, the drugs used and their dosage were as follows:
| |
| :500-750 mg tablet daily (10-15 mg/kg). |
| :750-1000 mg tablet daily (15 mg/kg). |
| :150 mg tablet OD (4 mg/kg). |
Pyridoxine (vitamin B6) tablet usually in a dose of 40 mg daily was supplemented whenever isoniazid was used.11
Hydrocortisone phosphate 100-200 mg IV 6 hourly was administered at the beginning of institution of ATT, whenever patient's general condition was poor and the tubercular infection was severe.12 This was given mainly for the suppression of tubercular endotoximic reaction arising from sudden release of endotoxins from the lysis of a large number of tubercle bacilli at a time by the combination of strong tubercular bactericidal drugs.13, 14 Sometimes we have observed patients having succumbed to such reaction.15-17 Sometimes systemic steroid in form of prednisolone tablet 0.5 to 1 mg per Kg body weight was also used during the first 4 to 12 weeks of ATT in patients of intracranial, pericardial, intestinal, peritoneal, tracheobronchial lymph nodal TB, to minimise fibrosis and consequent morbidity arising from contructure, adhesion and obstruction due to fibrosis.
The antitubercular drugs combination and regimens were selected on individual patient's requirement. The common schedule of 4 drugs (HREZ) daily about ½ an hour before breakfast for 2 months (Consolidation phase), followed by 2 drugs (HR) daily ½ an hour before breakfast for at least 4 months (Continuation phase) was followed. But in most of these cases, as these were other than usual form of pulmonary TB, total duration of ATT was longer than 6 months.
In severe infection, consolidation phase with 4 or more drugs combination, was extended up to 3 or 4 months.
In patients where H and/or R had to be withheld because of drug induced hepatitis the E, S and Cipro were continued beyond 2 months consolidation phase. Reintroduction of H and R later was possible by giving it in desensitisation fashion i.e. starting in a small dose, then building the dose up gradually until the full dose was attained.18 After about 8 weeks of successful reintroduction of H and R, other anti-TB drugs were discontinued. As the benefit of H and/or R was lost to these patients during the initial phase of the therapy course, total duration of ATT was made prolonged.
Total duration of therapy course was more than 6 months in these cases. For intracranial TB, it was more than 18 months; for osseous TB, around 18 months; for miliary and disseminated TB, around 12 months. Extended period of ATT was adopted to minimise the chance of recurrence of the disease. When the patient tolerated the therapy well during the consolidation phase, no untoward effect from the drugs (except in one patient) was encountered during the extended period of therapy. Most of these patients’ compliance with the long continued therapy was satisfactory; and the treatment cost was low. There was no incidence of recurrence of the disease, so far, after the completion of ATT.16
These patients were followed up in the outpatient clinic at 3 to 8 weeks intervals. Liver function tests were carried out 1 to 3 days before each visit to the clinic. Other biochemical and haematological analysis were done when required. Incidence of drug-induced hepatotoxicity was occasional, and it could be corrected by manipulation of the drug selection.
In only few cases, a resistant strain infection was suspected. Poor treatment out-come in terms of improvement in symptoms and signs, laboratory tests and imaging were considered to be the criterion of resistant mycobacterial infection. In these patients, the number of anti-TB drugs and duration of ATT were extended, until the lesions have resolved in all respects for more than 3 months.19, 20
21Symbols and Abbreviations Used
AFB
=Acid fast bacilli
Alk phos
=Alkaline phosphatase
ALT
=Alanine aminotransferase
AST
=Aspartate transaminase
ATT
=Antitubercular therapy
BAL
=Bronchoalveolar lavage
BP
=Blood pressure
Cipro
=Ciprofloxacin
CNS
=Central nervous system
CT
=Computed tomography
ECG
=Electrocardiography
ESR
=Erythrocyte sedimentation rate
E
=Ethambutol
H
=Isoniazid
Hb
=Haemoglobin
HIV
=Human immunodeficiency virus
K
=Potassium
LDH
=Lactic dehydrogenase
MRI
=Magnetic resonance imaging
Na
=Sodium
R
=Rifampicin
RR
=Respiration rate
S
=Streptomycin
TB
=Tuberculosis
Temp
=Temperature
US
=Ultrasound
WBC
=White blood cell
Z
=Pyrazinamide