Dermatologic Therapy, Vol.

21, 2008, 154–161 Printed in the United States · All rights reserved

Copyright © Blackwell Publishing, Inc., 2008

DERMATOLOGIC THERAPY
ISSN 1396-0296

Blackwell Publishing Inc

Management of cutaneous tuberculosis

EVANGELINE B. HANDOG*,†, TERESITA G. GABRIEL† & ROSARIO TRINIDAD V. PINEDA‡
*Department of Dermatology, Asian Hospital Medical Center, Philippines, †Research Institute for Tropical Medicine, Department of Health, Philippines, ‡Philippine Dermatological Society, Philippines

ABSTRACT: Cutaneous tuberculosis (TB) is an extrapulmonary form of tuberculosis, which may be classified based on the immunologic state of the host. Chemotherapy still remains the treatment of choice. The management of cutaneous TB follows the same guidelines as that of TB of other organs, which can be treated with a short course four-agent chemotherapeutic regimen given for 2 months followed by a two-drug regimen for the next 4 months. This chapter highlights current treatment recommendations for cutaneous TB. The important factors to consider in the choice of optimal treatment includes the type of cutaneous involvement, stage of the disease, level of immunity, and general condition of the patient. The highest priority in any cutaneous TB control program is the

proper, accurate, and rapid detection of cases and the availability of chemotherapy to all tuberculosis patients until cure. Contact tracing is also an important component of efficient tuberculosis control.
KEYWORDS: cutaneous tuberculosis, management, TB, tuberculosis

Introduction
The genus Mycobacterium causes more suffering for humans than all other bacterial genera combined (1). Many authors have reported tuberculosis, caused by mycobacterium tuberculosis and which was classified as pulmonary and extrapulmonary to have been part of human history since prehistoric times and up to now, remains a major public concern in developing countries. According to the World Health Organization, there are more than 14 million people living with TB as of March 2007. In 2005, 3.9 million of the estimated 8.8 million new TB cases worldwide were diagnosed by laboratory testing and 629,000 were HIV positive. Global access to TB treatment is improving but remains low. Those with active TB who receive no treatment can infect an average of 10–15 people annually (2).
Address correspondence and reprint requests to: Evangeline B. Handog, MD, FPDS, FAAD, Room 316 Asian Hospital and Medical Center, 2205 Civic Drive, Filinvest Corporate City, Alabang, Muntinlupa City, Metro Manila, Philippines, 1780, or email: handogmd@pacific.net.ph.

TB continues to be in the top 10 causes of morbidity and mortality in the Philippines. The declining incidence of cutaneous TB worldwide was the result of improved therapy, reduction in the size of the active reservoir of infection, and increased immunoresistance to infection. However, it was also noted that cutaneous TB re-emerged in those parts of the world where the incidence of HIV infection and multidrug-resistant tuberculosis is high. One vital factor in curbing the increase in cutaneous TB is the initiation of proper treatment that not only encompasses an effective regimen but also ensures compliance with and response to management. The important factors to determine the clinical presentation of cutaneous TB include the pathogenicity of the organism, its antibiotic resistance profile, the portal of infection, the immune status of the host, particularly the presence or absence of acquired immunodeficiency syndrome (AIDS) secondary to infection with human immunodeficiency virus (HIV), and various local factors in the skin such as relative vascularity, trauma, lymphatic drainage, and proximity to lymph nodes.

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Classification and diagnosis Diagnosis of cutaneous TB is challenging and requires the correlation of clinical and histopathologic findings and diagnostic testing. The bacillary load in cutaneous TB is usually less than in pulmonary TB (3). but the mucous membrane and skin occasionally show primary involvement. Department of Health. 155 . In addition to traditional acid-fast bacilli (AFB) smears and cultures. ulcerative lesions. The usual portal of entry of M. 1). or scarring reactions. Philippines are listed below. nodules. warty tumors. Mycobacterial culture still remains to be the most reliable method in determining the presence of live mycobacteria and their sensitivity to antibiotics and to monitor treatment response. there has been increased utilization of polymerase chain reaction because of its rapidity. The four most common forms of cutaneous TB encountered at the Research Institute for Tropical Medicine. 1. The majority of cases of cutaneous TB are a manifestation of systemic involvement. sensitivity. Classification of cutaneous TB may be based on the immunologic state of the host (FIG. tuberculosis includes the lungs and the intestines. and specificity. Cutaneous involvement may include papules. plaques.Management of cutaneous tuberculosis FIG. Classification of cutaneous tuberculosis.

A 57-year-old female patient with a soft. and hypopigmented atrophic center on the right leg. Lupus vulgaris. brownish crusts. hypopigmented and atrophic scar on the left anterior shin. atrophic scars over the course of a few weeks. 156 . 2. FIG. The skin lesion first presents as firm. 3). Scrofuloderma. FIG. warty. The most serious complication of long-standing lupus vulgaris is the development of carcinoma with squamous cell carcinoma outnumbering basal cell carcinoma (FIG. As the infiltrate enlarges. 2). dusky-red papules. It is extremely chronic and without treatment. Tuberculosis verrucosa cutis Tuberculosis verrucosa cutis is also known as warty TB. nontender. Ulcers and sinuses develop and discharge watery and purulent or caseous material. an ulcerative or mutilating form. plaque-like form of cutaneous TB occurring as a result of the inoculation of organisms into the site of a previously infected patient who usually has moderate or high degree of immunity. Because of the virulence and resistance to phagocytosis by M. Scrofuloderma Lupus vulgaris Lupus vulgaris is an extremely chronic and progressive form of tuberculosis of the skin that occurs in individuals with moderate immunity and a high degree of tuberculin sensitivity. it softens. Spontaneous involution does occur and results in sunken atrophic scars (FIG. erythematous plaque with erosions and brownish crust. a vegetating form. 4). It is an indolent. freely movable asymptomatic infiltrate. 3. hands. verrucous. 5). The disease is progressive and leads to significant impairment of function and disfiguration. The legs. More often it occurs in the parotidal. and supraclavicular regions as well as on the lateral aspects of the neck.Handog et al. irregular border. and feet are the sites of predilection (FIG. elbows. New crops may continue to appear over months or years. tender. also known as tuberculosis colliquativa cutis. The lesions progress slowly. Sinusoidal tracts undermine the skin and clefts dissecting subcutaneous pockets alternate with soft nodules (FIG. Papulonecrotic tuberculids Papulonecrotic tuberculids consist of recurring crops of symmetrical. The manifestations of the disease in the skin are influenced by previous infection or immunity and by the route of infection. knees. Tuberculosis verrucosa cutis. a tumorlike form. subcutaneous nodule or as well-defined. A 34-year-old male patient with a soft. verrucous plaque with seropurulent discharge. is a subcutaneous TB that leads to cold abscess formation and a secondary breakdown of overlying skin. hard. and a papulonodular form. submandibular. its course usually extends over the years. and if untreated may persist for many years. Clinical presentations include a plaque or planar form. These form crusts or may ulcerate leaving pigmented.

movable. whereas macrophages and their derivatives are characteristically seen in the cellular response. Cutaneous TB is an extra-pulmonary form of TB being treated with a short-course four-agent chemotherapy regimen given for 8 weeks followed by a two-drug regimen for the next 16 weeks. except that some authorities recommend higher doses of isoniazid and rifampicin. Surgical intervention is useful for the treatment of isolated lupus vulgaris and tuberculosis verrucosa cutis and some cases of scrofuloderma. intensive chemotherapy includes daily isoniazid. with peak serum level at 2–4 hours and elimination within 24 hours. max 600 mg 20–25 mg/kg. Rarely will TB of the skin be confined as strictly a cutaneous disease like tuberculosis verrucosa cutis and lupus vulgaris. 157 . Source: Based on American Thoracic Society. max 2 g 15–20 mg/kg Thrice-Weekly dose 15 mg/kg. nonfluctuant. The recommended regimen comprises an initial bactericidal or intensive phase and a continuation or sterilizing phase. and either ethambutol or streptomycin for 8 weeks (Tables 1 and 2).Management of cutaneous tuberculosis FIG. Scrofuloderma. three times weekly or two times weekly for 16 weeks (1). 4. These drugs are well absorbed after oral administration. which is defined as the ability to rapidly reduce the number of viable organisms and render patients noninfectious. max 900 mg 10 mg/kg. tuberculosis. This group of drugs also has low rates of induction of drug resistance and has sterilizing activity as measured in terms of the ability to prevent relapses. The initial. pyrazinamide. The initial phase of the regimen is directed toward the rapid destruction of a large population of mycobacterium and resolution of symptoms. the patients become noninfectious. max 300 mg 10 mg/kg. It aims to cure the disease as rapidly as possible to prevent relapses and the emergence of resistant strains. erythematous nodule on the right lateral aspect of the neck. Firstline drugs that are highly effective and which are used mainly in the initial treatment of susceptible organisms are isoniazid. neutrophils are completely ineffective in dealing with this bacterial infection. If therapeutic response is observed in isoniazid and rifampicin. the level of immunity. and the general conditions of the patient. rifampicin. Treatment The management of cutaneous TB follows the same guidelines as that of TB of other organs. Optimal treatment can be achieved. A 20-month-old male patient with a firm. these drugs are given either daily. considering the following factors: the type of cutaneous involvement. Recommended dosage for initial treatment of cutaneous tuberculosis Drug Isoniazid Rifampicin Pyrazinamide Ethambutol a Daily dose 5 mg/kg. The continuation phase aims to eliminate the remaining “dormant” organisms. the stage of the disease. Rifapentine Table 1. After completion of this phase. Chemotherapy still remains the treatment of choice. These lead to giant cell granuloma formation with or without necrosis and this underlies the varied clinical presentations of this infection (4). which may exist without evidence of associated internal TB. 20–30 mg/kg intermittent 10–20 mg/kg Dosage for children is similar. rifampicin. pyrazinamide. max 3 g 25 –30 mg/kg Childrena 10–15 mg/kg daily. These agents are recommended on the basis of their bactericidal activity. and ethambutol. Infectious Disease Society of America and Centers for Disease Control and Prevention. max 600 mg 30 –40 mg/kg. nontender. smooth. as the lesions in the skin often represent hematogenously or lymphatically dispersed disease from internal foci of infection.

Second-line drugs used mainly in the treatment of patients with drug-resistant mycobacteria include these injectable drugs: streptomycin (formerly a first-line agent). amikacin. and patients with conditions such as chronic renal failure. and rifabutin are two drugs related to to Rifampicin which can be used as substitutes in the treatment of cutaneous TB. levofloxacin. Recently. malnourished persons. and capreomycin.Handog et al. 158 . pyridoxine (10–25 mg/day) should be added to the regimen given to persons at high risk of vitamin B6 deficiency such as alcoholics. ethionamide. 5. pregnant and lactating women. and these oral drugs: pyrazinamide. A 32-year-old female patient with erythematous papules evolving into pustules developing central necrotic crust and healing with depressed scars on the chest. diabetes. fluoroquinolone antibiotics such as ofloxacin. Papulonecrotic tuberculid. and HIV infection or AIDS. To prevent isoniazid-related neuropathy. which are also associated with neuropathy (5). kanamycin. back and arms. hence they are only used for patients with cutaneous tuberculosis resistant to the first-line agents. FIG. and cycloserine. These drugs have lower degree of efficacy and a higher degree of intolerability and toxicity.

The provider-related factors that may promote compliance include proper education and encouragement of patients. Treatment regimen for cutaneous tuberculosis Initial or bactericidal phase Continuation or sterilizing phase Chemotherapy Rifampicin + isoniazid + pyrazinamide + streptomycin or ethambutol 2 months. there are still many TB patients who are not cured. and granulocyte/macrophage colony-stimulating factor (GM-CSF). the presence of concomitant medical condition like substance abuse. kanamycin. depending upon tolerance and response. makes it most likely for patients to be noncompliant to therapy. lack of social support. daily Rifampicin + Isoniazid 4 months. Factors leading to multidrug resistance include monotherapy. Both patient. Amikacin. FDCs are strongly recommended as a means of minimizing the possibility of prescription error and of the development of drug resistance as a result of monotherapy (5). DOT works by assigning a responsible person to observe or watch the patient take the correct medications daily during the whole course of treatment. although not yet established as a therapeutic options. interferon gamma. drug resistance. and insufficient number of active chemotherapeutic agents in a regimen. cycloserine. The long duration of treatment. or death.Management of cutaneous tuberculosis gatifloxacin. b a Pyrazinamide + ethambutol + quinolone antibiotic Streptomycin (or another injectable agentb) Throughout (18–24 months) Resistance to isoniazid and rifampicin Rifampicin + pyrazinamide + ethambutola Throughout (6 months) Resistance to isoniazid Table 2. daily 2/week or 3/week 6 months at least First-line drugs 6 months 18–24 months 159 . 6 months on the average. There are two established strategic approaches to address the problem of drug resistance and to ensure treatment compliance: directly observed treatment (DOT) and fixed-drug combination (FDC) products. and poverty. The best way to prevent the occurrence of drug resistance is through regular intake of drugs for the prescribed duration. act by helping control intracellular pathogens. interleukin 2 (IL-2). Treatment compliance is therefore a must. Poor treatment compliance may lead to the following outcomes: chronic infectious illness. and the provision of incentives and enablers such as meals and bus tokens (5). quinolone antibiotic. 1 injectable agentb + 3 of the following: ethionamide. Although effective anti-TB drugs are available in the developing countries. poor drug absorption. This is because many patients either stop or irregularly take their drugs. (Table 3) Cytokines. and moxifloxacin are commonly used as second-line drugs. para-aminosalicylicacid Throughout (24 months) Resistance to all first-line drugs 24 months Total duration of therapy A fluoroquinolone may strengthen the regimen for patients with extensive disease. suboptimal dosage. erratic drug ingestion. FDC products such as isoniazid/rifampicin. The patient-related factors include a lack of belief that the illness is significant and warrants treatment. isoniazid/rifampin/pyrazinamide. or capreomycin. and isoniazid/ rifampin/pyrazinamide/ethambutol are available as well. All agents should be discontinued after 2–6 months.and provider-related factors may affect compliance in the intake of anti-TB drugs. thereby shortening the duration of therapy and preventing drug resistance. omission of one or more of the prescribed chemotherapeutic agents. the offering of convenient clinic hours. TB patients who do not adhere to the prescribed regimen are likely to become drug resistant.

Guide in managing short course chemotherapeutic drug side effects Side effects Drugs responsible What to do? Minor side effects – patient should be encouraged to continue taking medicines Gastro-intestinal intolerance Rifampicin Give medication at bedtime Mild skin reactions Any kind of drugs Give anti-histamines Orange-/red-colored urine Rifampicin Reassure the patient Pain at the injection site Streptomycin Apply warm compress Rotate sites of injection Burning sensation in the feet as a result Isoniazid Give pyridoxine (vitamin B6): 100–200 mg of peripheral neuropathy daily for treatment 10 mg daily for prevention Arthralgia as a result of hyperuricemia Pyrazinamide Give aspirin or NSAID Flu-like symptoms (fever. resume treatment Rifampicin and and monitor clinically Pyrazinamide) Impatient of visual acuity and color vision Ethambutol Discontinue Ethambutol and refer to an as a result of optic neuritis ophthalmologist Hearing impairment. Second-line drugs Drug Capreomycin Kanamycin Ethionamide Para-aminosalicylic acid (PAS) Cycloserine Ciprofloxacin Ofloxacin Amikacin Clofazimine Daily dose (maximum dose) 15–30 mg/kg (1 g) 15–30 mg/kg (1 g) 15–20 mg/kg (1 g) 150 mg/kg (12 g) 15–20 mg/kg (1 g) 500–1000 mg/kg 400–800 mg/day 15 mg/kg 100–300 mg/day Testing for HIV is recommended for all patients diagnosed with TB because they may require longer courses of therapy. Rifampicin Give antipyretics inflammation of the respiratory tract) Major side effects: discontinue taking medicines and refer to physician immediately Severe skin rash as a result of Any kind of drugs Discontinue anti-TB drugs and refer hypersensitivity (especially to Physician Streptomycin) Discontinue anti-TB drugs and refer to Jaundice as a result of hepatitis Any kind of drugs Physician (especially Isoniazid.Handog et al. Because viable mycobacteria can still be cultured from clinically healed lesions. since multidrug-resistant TB is common in some communities. 2001. every effort should be made to culture the organism for sensitivity testing. In these cases. Table 3. The most common adverse reaction is hepatitis. If symptoms subside. especially during the intensive phase (Table 4). the response to treatment must be assessed clinically. anemia. muscle pains. Department of Health. ringing of the ear and Streptomycin Discontinue Streptomycin and refer to dizziness as a result of the damage of the Physician eighth cranial nerve Oliguria or albuminuria as a result of renal Streptomycin Discontinue anti-TB drugs and refer to disorder Rifampicin Physician Psychosis and convulsion Isoniazid Discontinue Isoniazid and refer to Physician Thrombocytopenia. Patients should be carefully educated about the signs and symptoms of drug-induced hepatitis such tea-colored urine and loss of appetite and should be instructed to discontinue promptly and to consult with their Table 4. Bacteriologic monitoring of patients with cutaneous tuberculosis is not feasible and more difficult compared to that for pulmonary tuberculosis. During therapy. 160 . Completion of therapy is defined more accurately by the total number of doses taken than by the length of treatment. shock Rifampicin Discontinue anti-TB drugs and refer to Physician Source: Manual of Procedures for the National Tuberculosis Control Program. drug toxicity should be observed. In addition. Republic of the Philippines. Closely monitor the occurrence of minor and major reactions to drugs. treatment should be continued for at least 2 months after complete involution of the lesions.

Barbagallo J.Management of cutaneous tuberculosis physicians.. McKee P. Harrison’s principles on internal medicine. (Document: WHO/Programmes and projects/Media center/Fact sheet). O’Brien R. et al. eds. 2. Additional strategies to prevent the spread of disease include BCG vaccination and treatment of persons with latent tuberculosis infection who are at high risk of developing active disease. it is highly recommended in low-prevalence countries with adequate resources to screen high-risk groups such as immigrants from high-prevalence 161 . Tager P. eds. Hyperuricemia and athralgia may be caused by pyrazinamide and are usually treated with by the acetyl salicylic acid. The best way to prevent cutaneous TB is to diagnose infectious cases rapidly and administer appropriate treatment until cure. on the other hand. Tuberculosis and other mycobacterial infections. Raviglione M. et al. liver and renal functions tests should be carried out before instituting therapeutic regimen. gouty arthritis would warrant the discontinuance of pyrazinamide. USA: Mc Graw Hill. Tappeiner G. 3. In: Kasper D. Am J Clin Dermatol 2002: 38: 319–328. In addition. PPD-positive high-risk persons should also be treated for latent infection. 4. Hypersensitivity reactions usually require the discontinuation of all drugs and rechallenge to determine which agent is the culprit (5). Hirsch R. Klaus W. USA: Mc Graw Hill. Weinberg J. Contact tracing is an important component of efficient tuberculosis control. 5. 2003: 1933–1945. Tuberculosis. Calonje E. 2005: 897–898. In: Freedberg I. eds. Granter S. This is an indication for patients to permanently discontinue the use of the said drugs upon appearance of these serious side effects. Cutaneous tuberculosis: diagnosis and treatment. Baseline laboratory examinations such as complete blood count. Conclusion The highest priority in any cutaneous TB control program is the proper and accurate detection of cases and the availability of short-course chemotherapy for all TB patients under proper case management conditions. Identification of active cases of tuberculosis should be followed by treatment. References 1. 2005: 962– 963. Fact sheet No 4: Tuberculosis. Ingleton R. Pathology of the skin. March 2007. countries and HIV-seropositive persons. There are reports of individuals developing autoimmune thrombocytopenia secondary to rifampicin and optic neuritis secondary to ethambutol. Fitzpatrick’s dermatology in general medicine. WHO Media centre. World Health Organization. China: Mosby..