Mycobacterial Infections The genus mycobacterium contains more than 80 species , most of which are harmless environmental saprophytes A few species are important pathogens of humans and other vertebrates. The most important obligate human pathogens are Mycobacterium tuberculosis and M. lepra.

Tuberculosis Mycobacterium bovis infection, endemic in cattle, can be spread to humans by milk, but human infection with this organism is now rare in countries where cattle have been vaccinated against tuberculosis and milk is pasteurized. One-third of the world’s population is infected with TB. Nine million new infections and 2 million disease-related deaths occur per year

Classification Inoculation from an exogenous source: primary inoculation tuberculosis and tuberculosis verrucosa cutis. Endogenous cutaneous spread contiguously or by autoinoculation: scrofuloderma, tuberculosis cutis orificialis. Hematogenous spread to the skin: lupus vulgaris; acute miliary tuberculosis; tuberculosis ulcer, gumma, or abscess; tuberculosis cellulitis. Tuberculids: erythema induratum (Bazin disease), papulonecrotic tuberculid, and lichen scrofulosorum.

Inoculation Cutaneous Tuberculosis from an Exogenous Source

It occurs chiefly in children and affects the face or extremities. Primary Inoculation Tuberculosis (Primary Tuberculosis Complex, Tuberculosis Chancre) Develops at the site of inoculation (traumatized skin) into a tuberculosis-free individual. It occurs chiefly in children and affects the face or extremities. The earliest lesion, appearing 2-4 weeks after inoculation, is a painless brown-red papule, witch develops into an indurated nodule or plaque that may ulcerate. This is the tuberculous chancre.

Primary Inoculation Tuberculosis (Primary Tuberculosis Complex, Tuberculosis Chancre) Prominent regional lymphadenopathy appears 3-8 weeks after infection and, occasionally, cold, suppurative, and draining lesions may appear over involved lymph nodes. Primary complex occurs on the mucous membranes in about one-third of patients. Spontaneous healing usually occurs within a year, with the skin lesion healing first, then the lymph node, which is often persistently enlarged and calcified.

D.D With chancriform conditions of deep fungal or bacterial origin, syphilis, leishmaniasis, atypical mycobacterial disease, pyogenic granuloma.

Tuberculosis Verrucosa Cutis It occurs from exogenous inoculation of bacilli into the skin of a previously sensitized person with strong immunity against M. tuberculosis. The tuberculin test is strongly positive. The prosector’s wart resulting from inoculation during an autopsy is the prototype of tuberculosis verrucosa cutis. Frequent locations are on the dorsa of the fingers and hands in adults, and the ankles and buttocks in children Clinically the lesion begins as mall papules. Which become hyperkeratotic, resembling a wart. Lesions are almost always solitary, and regional adenopathy is usually present only if secondary bacterial infection occurs.

Tuberculosis from an endogenous Source by direct extension or autoinoculation

Scrofuloderma It is tuberculous involvement of the skin by direct extension, usually from underlying tuberculous lymphadenitis. It occurs frequently over the cervical lymph nodes but also may occur over bone or around joints. Clinically, the lesions begins as subcutaneous masses, which enlarge to form nodules. Suppuration occur centrally. Heals with characteristic cordlike scars

Tuberculosis Cutis Orificialis it is a form of cutaneous TB that occurs at the mucocutaneous borders of the nose, mouth, anus, urinary meatus, and vagina. It is caused by autoinoculation from underlying visceral TB. Lesions ulcerate from the beginning and extend rapidly, with no tendency to spontaneous healing. It indicates failing resistance to the disease. Consequently, tuberculin positivity is variable but usually present.

Cutaneous Tuberculosis from Hematogenous Spread

Lupus Vulgaris May appear at sites of inoculation, in scrofuloderma scars, or most commonly at distant sites from the initial infectious focus. Approximately half of cases will have evidence of TB elsewhere. Because lupus vulgaris is associated with moderately high immunity to TB most patients will have a positive tuberculin test.

Lupus vulgaris typically is a single plaque composed of grouped red-brown papules, which, when blanched by diascopic pressure, have a pale brownish yellow or ‘apple-jelly’ color. The papules tend to heal in one area and progress in another. Expanding by the development of new papules at the periphery, witch coalesce with the main plaque. The disease is destructive, frequently causes ulceration, and on involution leaves deforming scars. Ninety percent of lupus vulgaris lesions occur on the head and neck.

DD Differentiation from tertiary syphilis, chronic discoid lupus erythematosus, leprosy, systemic mycosis, and leishmaniasis

Miliary (Disseminated) Tuberculosis Appears in the setting of fulminant TB of the lung or meninges. It is most common in children but may occur in adults. Most common seen in patients with AIDS and may also follow infections illnesses that reduce immunity, especially measles. Because this represents uncontrolled hematogenous infection, the tuberculin test is negative. Lesions are generalized and may appear as erythematous macules or papules, pustules, subcutaneous nodules, and pruritic ‘vasculitis’ lesions

Metastatic Tuberculous Abscess or Ulceration The hematogenous dissemination of mycobacteria from a primary focus may result in firm, nontender erythematous nodules, which soften, ulcerate, and form sinuses. These are usually seen in children, and most patients have decreased immunity from malnutrition, intercurrent infection, or an immunodeficiency state.

Tuberculous Cellulitis: It is unusual manifestation of TB was reported in a patient who had been on chronic corticosteroids and developed clinical cellulitis.

Tuberculids They are a group of skin eruptions associated with an underlying or silent focus of TB; induced by hematogenous dissemination to the skin. They are diagnosed by: Clinical features and histological findings Positive tuberculin test Sometimes finding of TB at a distant site Resolution of the eruption with antituberculous therapy

Papulonecrotic tuberculid Papulonecrotic tuberculid. Typical lesions are firm, inflammatory papules that become pustular or necrotic. Lesions are symmetrically distributed on the extensor extremities, especially on the tips of the elbows, knees, dorsal surfaces of the hands and feet, face and ears, and glans penis. Lichen Scrofulosorum. consists of group of indolent, minute, keratotic, discrete papules, scattered over the trunk. Erythema Induratum (Bazin disease): it is chronic and more common in women of middle age (80%). Lesions favor the posterior lower calf. Individual lesions are tender, erythematous or violaceous, 1-2cm subcutaneous nodules. Lesions resolve spontaneously and often heal with scarring.

DD TB. of the skin should be differentiated from : leprosy , leishmaniasis , deep mycosis , non-TB mycobacterial infections , syphilis and sarcoidosis .

Diagnosis: The only absolute criteria for diagnosis of Cutaneous TB. Are: positive culture of M. TB. from the lesions , or successful guinea-pig inoculation , or mycobacterial DNA identification by polymerase chain reaction .

1. The presence of active proven TB. elsewhere in the body . Diagnosis: Other indications to ward the diagnosis which are by themselves unreliable , include the followings : 1. The presence of active proven TB. elsewhere in the body . 2. The presence of acid-fast bacilli in the lesion itself 3. The histopathology: the fully formed tubercle consists of a focus of epithelioid cells containing, a number of Langhans giant cells and a surrounding infiltrate of mononuclear cells. 4. A positive tuberculin test . 5. The clinical and physical signs . 6. The effect of specific therapy .

Treatment: 1. General measures- search for an underlying focus of TB and coexistent infections like HIV . 2. Drugs therapy : (Standard drug regimens are) A. Six months regimens : including four drugs in the initial 2months phase ( rifampicin , isoniazid , pyrazinamide , plus streptomycin or Ethambutol ) , followed by continuation 4months phase ( rifampicin and isoniazid) , are highly effective in patients with fully sensitive organisms . B. One year regimens : which include initial 2months phase of 4drugs and continuation 10months phase of 2drugs .

Hansen’s Disease The world health organization (WHO) committed itself to eliminating Hansen’s disease as a public health problem by the year 2000. Elimination (not eradication) is considered as a prevalence of ˂1 case in 10000 in any country. All cases of human and animal leprosy are caused by the same organism, M. lepra is a weakly acid-fast organism that has not been successfully cultured in vitro. It grows best at temperatures (300 C) below the core body temperature of humans. This explains the localization of leprosy lesions to cooler areas of the body and sparing of the midline and scalp. principally affecting peripheral nerves and skin The incidence of leprosy remains stable at around 800000 new cases annually , with a high rates of childhood cases . 86% of leprosy patients reside in 6 countries ( India , Brazil , Indonesia , Myanmar , Madagascar and Nepal) .

Classification: High resistance Unstable resistance No resistance Tuberculoid Borderline Borderline Borderline Lepromatous tuberculoid lepromatous (TT) (BT) (BB) (BL) (LL) Lesions 1-3 few few or many many numerous Smear for 0 +1 +2 +3 +4 bacilli Lepromin +3 +2 + + 0 test Histology Epithelioid cells decreasing increasing histiocytes, Nerve destruction, granuloma, foam cell, sarcoid-like granuloma xanthoma-like

Leprosy may present with a broad spectrum of clinical disease depends upon immune response of the patient. The classification is based on clinical, bacteriologic, immunologic and histopathologic features. Patients who do develop clinical disease are broadly classified into two groups: patients with few organisms in their tissue are termed paucibacillary, and patients with large number of organisms are termed multibacillary. If the cell-mediated immune response against M. leprae is strong, the number of organisms will be low (paucibacillary), and conversely if this response is inadequate, the number of organisms will be high (multibacillary).

clinical features Tuberculoid Lepromatous Clinical features: The initial clinical lesion may a single hypopigmented patch, perhaps with slight anesthesia .Characteristic of lesions of polar leprosy:  clinical features Tuberculoid Lepromatous Number of lesions 1-10 Hundreds, confluent Distribution Asymmetrical Symmetrical Definition and clarity Defined edge, markedly hypopigmented Vague edge, slight hypopigmentation

Anaesthesia Early, marked, defined, localized to skin lesions or major peripheral nerve Late, initially slight, ill-defined, but extensive, over ‘cool’ areas of body Autonomic loss Early in skin and nerve lesions Late, extensive as for anaesthesia Nerve enlargement Marked, in a few nerves Slight but widespread Mucosal systemic Absent Common, severe during type 2 reaction Number of M. leprae Not detectable Numerous in all affected tissues

Diagnosis: the diagnosis is usually made clinically on the basis of two out of three characteristic findings, or by demonstration of acid-fast bacillus in slit-skin smears or by histology. The cardinal signs are: Anaesthesia of a skin lesions Thickened nerves Typical skin lesions.

The investigations include Slit-skin smears: If the organisms are found, the patients are said to be multibacillary. If the results are negative they are called paucibacillary. Skin biopsies from skin or nerve lesions. Lepromin test: the Lepromin test is a non-specific. It is strongly positive in TT, weakly positive in BT, negative in BB, BL and LL. It is not use for diagnosis. Serologic tests to detect antibodies against M. leprae. They are universally positive in patients with multibacillary disease in whom the diagnosis is not difficult. In paucibacillary patients, these tests are often negative.

Treatment Hansen’s Disease Center in the USA: Paucibacillary cases the recommendation is 600 mg\day of rifampin and 100 mg\day of dapsone for 12 months. Multibacillary cases receive 100 mg\day of dapsone, 50 mg\day of clofazimine, and 600 mg\day of rifampin; for 2 years The WHO recommendation is shorter and cheaper. Paucibacillary cases is 600 mg of rifampin once a month for 6 months and 100 mg\day of dapsone for 6 months. Multibacillary cases are treated with four drugs. Rifampin 600 mg and clofazimine 300 mg, once a month, are taken with dapsone 1oo mg\day and clofazimine 50 mg\day.

Reactional States Fifty percent of patients will experience a reaction after the institution of multidrug therapy. Reactional states are divided into two forms, called, type 1 and type 2 reactions. Type 1 reactions are caused by cell-mediated immune inflammation and occur in patients with borderline leprosy (BT, BB, BL). Type 2 reactions are mediated by immune complexes and occur in lepromatous patients (BL, LL).

Management for reactional States It is not advisable to discontinue or reduce antileprosy medication. Type 1 reactions are usually managed with systemic corticosteroids. Clofazimine, cyclosporin have some activity against type 1 reactions. Thalidomide has been demonstrated to be effective against erythema nodosum leprosum.