Tuberculosis and tuberculids

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Tuberculosis and tuberculids

Yasaman Mansouri and John Berth-Jones

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

Cutaneous manifestations of infection with Mycobacterium tuberculosis are varied and are influenced considerably by the immune status of the patient. Cutaneous tuberculosis (TB) is often misdiagnosed due to its diverse clinical features and the difficulty demonstrating acid-fast bacilli on histology specimens. Cutaneous inoculation with M. tuberculosis can occur from an endogenous source, via lymphatic, hematogenous or contiguous spread, and causes periorificial TB, lupus vulgaris (LV), scrofuloderma, acute miliary TB, and tuberculous gumma. LV can also result from primary inoculation of the skin from an exogenous source, although this usually leads to tuberculous chancre and tuberculosis verrucosa cutis (warty TB). The tuberculids are ‘hypersensitivity’ reactions to extracutaneous sources of M. tuberculosis (tuberculous antigen) in individuals with high levels of immunity. Skin biopsy specimens from tuberculids seldom reveal mycobacteria histologically, although more sensitive PCR techniques do sometimes detect mycobacterial antigens. The tuberculids include erythema induratum of Bazin, erythema nodosum, lichen scrofulosorum, papulonecrotic tuberculid, and nodular tuberculid. Tuberculids respond to treatment of the underlying tuberculosis.

Management strategy

Clinical examination, typical histological findings and the presence of M. tuberculosis in tissue culture remains the gold standard method for diagnosis of TB. Early diagnosis is essential, to prevent further spread of disease.

Newer tests have overtaken the tuberculin skin tests (TST), which can show false positive results in individuals with previous bacille Calmette–Guérin (BCG) vaccination, as well as those infected with M. avium, and be falsely negative in the presence of immunosuppression. Interferon-γ release assays (IGRA) such as T-SPOT assay TB test (T-SPOT), and QuantiFERON-TB Gold test (QTF-G) have high specificity for identification of M. tuberculosis infection and require only one patient visit.

Identification of acid-fast bacilli in tissue cultures often fails as cutaneous TB cases are often paucibacillary. Polymerase chain reaction (PCR) is being used more frequently because of its high sensitivity and specificity.

Once cutaneous TB has been diagnosed, it is imperative to search for an extracutaneous focus of infection. Contact tracing is an important component of efficient TB management. HIV testing is recommended in all patients with diagnosed or suspected TB.

The aims of treatment are to rapidly cure the patient, to reduce transmission of TB to others, and to prevent the development and transmission of drug resistance. The standard treatment regimens recommended are based on controlled trials carried out for pulmonary tuberculosis. The standard 6-month regimen for adults comprises rifampicin (10 mg/kg), isoniazid (INH) (5 mg/kg), pyrazinamide (35 mg/kg), and ethambutol (15 mg/kg) for the initial 2 months of ‘intensive phase treatment’, followed by rifampicin and INH for a further 4 months in the ‘continuation phase’, ideally in fixed-dose combinations. Daily dosing throughout treatment is preferred. Occasionally longer treatment regimens may be necessary to achieve a complete cure, such as in HIV positive cases. Multidrug-resistant tuberculosis should be managed at specialist centers.

Specific investigations

First-line therapies

imageAntituberculous drugs A

Treatment of Tuberculosis: Guidelines for National Programmes, 4th ed.

World Health Organization, Geneva. 2009.

New patients with pulmonary TB should receive a regimen containing 6 months of rifampicin. The essential anti-TB drugs recommended are isoniazid (H) (5 mg/kg), rifampicin (R) (10 mg/kg), pyrazinamide (Z) (25 mg/kg), streptomycin (S) (15 mg/kg), and ethambutol (E) (15 mg/kg). The recommended regimen is 2 months of HRZE followed by 4 months of HR. The WHO recommends that daily dosing throughout the duration of therapy (two HRZE/four HR) is optimal for all newly diagnosed patients with TB. The WHO no longer recommends omission of ethambutol during the intensive phase of treatment for patients with a low risk of resistance to INH. In tuberculous meningitis, ethambutol should be replaced by streptomycin.

Comparative efficacy of drug regimens in skin tuberculosis.

Ramesh V, Misra RS, Saxena U, Mukherjee A. Clin Exp Dermatol 1991; 16: 106–9.

Three antituberculous drug regimens were employed to study the response in 90 patients with cutaneous TB. The first two regimens contained rifampin (adults 450 mg, children 15 mg/kg), INH (adults 300 mg, children 5 mg/kg), and either pyrazinamide (adults 1500®mg, children 30 mg/kg) or thiacetazone (adults 150 mg, children 4 mg/kg); the third regimen had rifampin and INH only. The patients with lupus vulgaris and warty TB cleared with all three regimens in 4 and 5 months for localized and generalized disease, respectively. Patients with scrofuloderma responded well to both triple-drug regimens, with the skin lesions subsiding completely within 5 months in the localized and 6 months in the widespread forms of the disease. However, 9 to 10 months, treatment was necessary in the group receiving isoniazid and rifampin.

Second-line therapies

imageExcision D
imageCalcipotriol E

[/level-membership-for-dermatology-category][not-level-membership-for-dermatology-category]

Tuberculosis and tuberculids

Yasaman Mansouri and John Berth-Jones

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

Cutaneous manifestations of infection with Mycobacterium tuberculosis are varied and are influenced considerably by the immune status of the patient. Cutaneous tuberculosis (TB) is often misdiagnosed due to its diverse clinical features and the difficulty demonstrating acid-fast bacilli on histology specimens. Cutaneous inoculation with M. tuberculosis can occur from an endogenous source, via lymphatic, hematogenous or contiguous spread, and causes periorificial TB, lupus vulgaris (LV), scrofuloderma, acute miliary TB, and tuberculous gumma. LV can also result from primary inoculation of the skin from an exogenous source, although this usually leads to tuberculous chancre and tuberculosis verrucosa cutis (warty TB). The tuberculids are ‘hypersensitivity’ reactions to extracutaneous sources of M. tuberculosis (tuberculous antigen) in individuals with high levels of immunity. Skin biopsy specimens from tuberculids seldom reveal mycobacteria histologically, although more sensitive PCR techniques do sometimes detect mycobacterial antigens. The tuberculids include erythema induratum of Bazin, erythema nodosum, lichen scrofulosorum, papulonecrotic tuberculid, and nodular tuberculid. Tuberculids respond to treatment of the underlying tuberculosis.

Management strategy

Clinical examination, typical histological findings and the presence of M. tuberculosis in tissue culture remains the gold standard method for diagnosis of TB. Early diagnosis is essential, to prevent further spread of disease.

Newer tests have overtaken the tuberculin skin tests (TST), which can show false positive results in individuals with previous bacille Calmette–Guérin (BCG) vaccination, as well as those infected with M. avium, and be falsely negative in the presence of immunosuppression. Interferon-γ release assays (IGRA) such as T-SPOT assay TB test (T-SPOT), and QuantiFERON-TB Gold test (QTF-G) have high specificity for identification of M. tuberculosis infection and require only one patient visit.

Identification of acid-fast bacilli in tissue cultures often fails as cutaneous TB cases are often paucibacillary. Polymerase chain reaction (PCR) is being used more frequently because of its high sensitivity and specificity.

Once cutaneous TB has been diagnosed, it is imperative to search for an extracutaneous focus of infection. Contact tracing is an important component of efficient TB management. HIV testing is recommended in all patients with diagnosed or suspected TB.

The aims of treatment are to rapidly cure the patient, to reduce transmission of TB to others, and to prevent the development and transmission of drug resistance. The standard treatment regimens recommended are based on controlled trials carried out for pulmonary tuberculosis. The standard 6-month regimen for adults comprises rifampicin (10 mg/kg), isoniazid (INH) (5 mg/kg), pyrazinamide (35 mg/kg), and ethambutol (15 mg/kg) for the initial 2 months of ‘intensive phase treatment’, followed by rifampicin and INH for a further 4 months in the ‘continuation phase’, ideally in fixed-dose combinations. Daily dosing throughout treatment is preferred. Occasionally longer treatment regimens may be necessary to achieve a complete cure, such as in HIV positive cases. Multidrug-resistant tuberculosis should be managed at specialist centers.