CUTANEOUS TUBERCULOSIS AND ATYPICAL MYCOBACTERIAL INFECTION
1. INTRODUCTION
Different Types of Cutaneous Tuberculosis
LV Lupus vulgaris
TVC Tuberculosis verrucosa cutis
SFD Scrofuloderma
EI Erythema induratum
PNT Papulonecrotic tuberculid
LS Lichen scrofulosorum
2. AETIOLOGY
Cutaneous mycobacterial infections are chronic granulomatous lesions affecting skin at various regions of the body. Micro-biologically they are classified as follows:
2.1 Tuberculous, pathogenic M tuberculosis M bovis M lepra M africanum 2.2 Non-tuberculous, potentially pathogenic
(i) Slow growing M marinum M ulcerans M kansasii M avium-intracellulare M scrofulaceum (ii) Rapid growing M fortuitum M chelonei 3. CLINICAL FEATURES
There are different clinical presentations in cutaneous tuberculous infections, depending on the virulence and number of bacilli infected, immunological status of the host and the route of infection. Traditionally the clinical types are divided into two groups :
(i) True cutaneous tuberculosis
Lupus vulgaris
Tuberculous verrucosa cutis
Scrofuloderma
Tuberculous chancre, gumma, cold abscess
Miliary tuberculosis
(ii) Tuberculids
Papulonecrotic tuberculid
Lichen scrofulosorum
Erythema induratum
3.1 True Cutaneous Tuberculosis
This group of cutaneous tuberculosis is infected through direct inoculation from an exogenous source, contiguous or haematogenous spread from an endogenous focus.
3.1.1 Lupus Vulgaris
This is a chronic, progressive and tissue-destructive form of cutaneous tuberculosis in patient with moderate or high degree of immunity. It occurs more common in females than in males. The classical lesions consist of reddish-brown plaque with "apple-jelly" colour on diascopy. The lesions progress by peripheral extension and central healing, atrophy and scarring. The areas of predilection are head and neck (80%), followed by arms and legs, then trunk. It can be associated with tuberculosis of lymph node, lung, bone and joint. In long-standing cases, patients may have scarring, deformity, squamous cell carcinoma, basal cell carcinoma or sarcoma. The main differential diagnosis includes discoid lupus erythematosus, sarcoidosis, leprosy, lupoid leishmaniasis, tertiary syphilis, deep fungal or atypical mycobacterial infection, granulomatous rosacea and Wegener's granulomatosis.
3.1.2 Tuberculosis Verrucosa Cutis
In the past, this condition was common in Chinese boys over the buttocks and knees. This is mainly due to their habit of playing and squatting in the streets with open-bottom trousers. It usually presents as an indolent, purplish or brownish red, warty and hyperkeratotic plaque lesion. It affects patients with moderate or high immunity through direct inoculation of the tubercle bacilli at sites of trauma. The areas of predilection are therefore over the buttock, knee, elbow, hand and finger. Its progression is usually very slow and spontaneous resolution may occur. This condition must be differentiated from lupus vulgaris, viral wart, mycobacteria marinum infection, chromomycosis, tertiary syphilis and hypertrophic lichen planus.
3.1.3 Scrofuloderma
This results from direct extension of an underlying tuberculous focus such as lymph node, bone or joint to the overlying skin, often associated with pulmonary tuberculosis. It is characterized by undermined ulcers, nodules, fistulae, sinuses and scar. The areas of predilection are neck, supraclavicular fossae, axillae and groin. The differential diagnosis mainly includes hydradenitis suppurativa, actinomycosis, sporotrichosis and atypical mycobacterial infection.
3.2 Tuberculids
It has been postulated that tuberculids are the result of hypersensitivity reaction to haematogenous dissemination of tubercle bacilli or their toxin in patients with moderate or high degree of immunity. Usually no identifiable focus of active tuberculosis can be detected and the tissue culture for acid-fast bacilli is often negative. There is still much controversy about these conditions.
3.2.1 Papulonecrotic Tuberculid
This condition usually presents with symmetrical crops of papular eruption that proceed to central necrosis, ulceration and depressed scar. It occurs predominantly in young adult, most commonly affecting the limbs. There may be history or distant foci of tuberculous infection. The main differential diagnosis includes prurigo simplex, papular eczema, folliculitis, leukocytoclastic vasculitis, pityriasis lichenoides et varioliformis acuta and secondary syphilis.
3.2.2 Lichen Scrofulosorum
This is a rare form of tuberculid, presenting with grouped lichenoid papules with perifollicular pattern over the trunk. It is frequently found in children or young adults and may be associated with tuberculosis of lymph node, bone or joint. The lesions often involute slowly in months without scar and then recur. This condition must be differentiated from lichenoid drug eruption, lichen nitidus, keratosis spinulosa, sarcoidosis, lichenoid syphilis and eruptive syringoma.
3.2.3 Erythema Induratum (Bazin)
This is a nodular tuberculid presenting with indolent inflamed deep-seated nodule and plaque, occurring bilaterally over the calves or feet. In severe case there may be necrosis, ulceration, depressed scar and pigmentation. It is more common in females than males. Usually there is no evidence of other distant tuberculous foci. The main differential diagnosis is erythema nodosum and other forms of nodular vasculitis.
3.3 Mycobacteria Marinum Infection
(Swimming pool or fish tank granuloma)
This is a chronic granulomatous infection of the skin caused by M marinum, acquired by inoculation through abrasions. It is more vulnerable in children and adolescents who frequently go to swimming pools, and among fishermen and fishmongers. The lesion commonly occurs on fingers, knuckles, elbows, knees and feet. Clinically it presents as an inflamed nodule, pustule, ulcer or abscess. Sporotrichoid spread may occur. The main differential diagnosis includes lupus vulgaris, sporotrichosis and leishmaniasis.
4. INVESTIGATIONS
4.1 Skin biopsy x histopathology (AFB stain)
x tissue culture for M tuberculosis
+ tissue culture for atypical mycobacterial and deep fungi
The histopathological diagnosis and clinical correlation are important because there is only a small percentage of cases with positive smear or culture. When the skin biopsy is performed, one must make sure that adequate tissue has been taken for both histological sections and tissue culture. Repeated skin biopsy may sometimes be necessary to make a final diagnosis. It is also important to specify on the laboratory form if one wants to do a culture for atypical mycobacteria. They require different temperature for growth in culture medium, for example, M marinum requires a temperature of 30-32 degree centigrade within 2-3 weeks.
4.2 Tuberculin Test
Mantoux test is usually done by starting with 1 unit of PPD intradermally over the forearm. If the result is negative, then the test is repeated with 10 units. The results are interpreted as follows:
Diameter of induration Conclusion
5-10 mm suspicious
> 10 mm positive
> 15 mm strongly positive
However this test is of limited diagnostic value locally because of the high incidence of exposure to mycobacteria and early vaccination of BCG. A negative result nevertheless excludes active tuberculosis, except the miliary form and diseases in immunocompromised patients.
4.3 Screening for Extracutaneous Tuberculosis
The presence of tuberculosis elsewhere provides supportive evidence in the diagnosis of cutaneous tuberculosis, especially in the tuberculids. Chest X-ray is mandatory. Other tests such as sputum, pus or early morning urine for acid-fast bacilli, lymph node biopsy or bronchoscopy should be done if indicated.
5. TREATMENT
Combination drugs therapy should be given to all true cutaneous tuberculosis such as lupus vulgaris, tuberculosis verrucosa cutis and scrofuloderma. Controversy exists about whether tuberculids should receive multiple drugs treatment. Papulonecrotic tuberculide is commonly treated with combination therapy, whereas erythema induratum and lichen scrofulosorum can be treated by suppressive therapy with isoniazid alone.
The regimens of antituberculous therapy used are summarized as follows :
5.1 Standard Drug Regimens (6 months)
(i) Initial phase (3-4 drugs daily for 2 months) Adult Child (a) Isoniazid 300 mg 5-8 mg/kg + (b) Rifampicin > 50 kg 600 mg < 50 kg 450 mg 10-12 mg/kg + (c) Pyrazinamide > 50 kg 2.0 gm 20-35 mg/kg < 50 kg 1.5 gm or Ethambutol < 60 days 25 mg/kg Not recommended > 60 days 15 mg/kg or Streptomycin 3/4 gm IMI 15-20 mg/kg (ii) Continuation phase (2 drugs daily for 4 months)
Isoniazid + Rifampicin (same dosage)
5.2 Intermittent Regimen (6 months)
(i) Initial phase (3-4 drugs thrice/week for 2 months) Adult Child (a) Isoniazid 600-800 mg 15 mg/kg + (b) Rifampicin 600 mg 15 mg/kg + (c) Pyrazinamide > 50 kg- 2.5 gm 20-35 mg/kg < 50 kg-2.0 gm or Ethambutol 30 mg/kg Not recommend or Streptomycin 1 gm IMI 15-20 mg/kg (ii) Continuation Phase (2 drugs thrice/week for 4 months)
Isoniazid + Rifampicin (same dosage)
All patients who have been put on antituberculous therapy should be closely monitored. The biochemical parameters like liver function test, renal function test and complete blood picture should be checked. Liver function test is mandatory and should be monitored at regular interval, as a lot of these drugs have hepatotoxic side-effects. In elderly patient or patient with renal impairment, the dosage of streptomycin should be reduced. Almost all the antituberculous drugs may cause drug eruptions. Some of these reactions may be serious, such as erythroderma and Stevens-Johnson syndrome. Elderly patient or alcoholic receiving isoniazid should have prophylactic treatment with pyridoxine. Patient who is receiving ethambutol should have regular ophthalmological check up.
5.3 Suppressive Therapy
This is used to treat tuberculids such as erythema induratum and lichen scrofulosorum. It can also be used as prophylactic treatment in patient who has been receiving systemic steroid or immunosuppressive drugs for other chronic cutaneous diseases.
Isoniazid 300 mg daily for 9 months to 1 year
Pyridoxine 10 mg daily as prophylactic measure or 100 mg daily as therapeutic measure against peripheral neuropathy
5.4 Treatment for M Marinum Infection
Medical :
(i) Cotrimoxazole tab 2 bd x 8-16 weeks
(ii) Minocycline 100 mg bd, Tetracycline 500 mg bd-qid x 8-16 weeks
(iii) Rifampicin + Ethambutol
Surgical :
(i) Electrodessication
(ii) Cryotherapy
(iii) Surgical excision
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