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CONTINUING EDUCATION

The cutaneous manifestations of mycobacterial do1seas e s

Robert Baker and Aliwzuddin Zurnla

.LI)~ohartrriitrn trd~crrulosis and certain atypical niyco- granulomas. Culture subsequently grew ibf. mirii7t/iii bacteria may cause a spectrum of cutaneous disease and (see below). Further questioning established that he m,iy sometimes pose difficult diagnostic problems kept tropical fish. He was treated with rifainpicin and (Table 1). This is especially true in irrimuno- etha~nbutolfor 12 weeky. His lesions had rerolved compromised patients, where even niycobacteria not within 6 weeks. previously thought to cuse disease niay do so. A high index of suspicion is required and unusual skin lesions CUTANEOUS MANIFESTATIONS OF presenting in these circ~unst~incesshould always be M. TUBERCULOSIS (TABLE 1) biopsied and sent for mycobacterial culture and staining and PCR where possible. Today, tuberculosis kills ni~repeople than any other infectious disease and a global epidemic is currently in CLINICAL CASE progress. Co-infection with HIV has led to the emerg- ence of a wide spectrum of clinical disease. Skin mani- A 37-year-old healthy, HIV-negative man presented festations are becoming increasingly coninion and these lvith a (,-week history ofa painless ulcer on his right will be suniniarized here. One of the most common niiddle finger. Subsequently, cold painless abscesses cutaneous nianifestations is ‘lupus vulgxis’ (Figure 2). developed on the dorsuni of his hand and forearm up It represents reinfection of the skin in individuals to the elbow (Figure 1). On exaniination he was well previously sensitized to tuberculosis (tuberculin positive). md afebrile. Blood investigations were normal apart It may appear as granulonimius nodules, ulcers, plaques ftom a moderately elevated ESR. Aspiration and biopsy and vegetations, frequently on the nose. fice and neck. \vcis subsequently performed 011 one of the abscesses on In the patient not sensitized to tir6cr.c-rilosis. iriocu- his forearm. Biopsy revealed non-caseating giant cell lation into the skin results in ‘I tuberculous chancre (3 firm nodule) with mociated regional lympha- denopathy. Where the individual is previously sensi- tized, there will be no lymphadenopathy. This is known as warty tuberculosis 01- ‘prosector’s wart’, so c~lledas it was once frequently contracted in the dissection room. The skin may also be afFeected in ‘scrofiiloderma’. where tuberculous processes involving subcutaneous tissues ulcerate aid form ‘ibscesses. In patient5 with advanced tuberculous disease of the viscera the mucous membranes may become involved. This is known as ‘orificial tuberculosis’. ‘Tuberculosis cutis niiliaris disseminata’ refers to heinatogenous dissemination of mycobacteria to the skin. It causes multiple papulo- vesicular lesions that heal with scarring. It occurs more frequently in patients with HIV.

Figure 1 Ulcerated lesion of Jf. ttiariiiiiiti (fish fancier’< There are several cutaneous iiiaiiifestations of- finger) with ascending abwesses 011 the forearm, resembling tuberculous infection which do not reveal the organism sporotrichosis. on culture. These are teriiied ‘tuberculids’. They have

460 Baker and Zumla: The cutaneous manifestations of mycobacterial diseases 46 1

Table 1 The cutaneous manifestations of mycobacterial dseases

Disease Organism

Lupus vulgaris i21. tuberculosis Tuberculous chancre Warty tuberculosis (prosector's wart) Tuberculosis irdiaris cutis dissemiuataa Orificial tuberculosis ? Tuberculids Erythema nodosum Scrofulodemma Fish fancier's finger, sporotrichoid Buruli/Bairnsdale ulcer Lymphadenitis/skin abscessed skin infiltration M. ccr~fiilacei~rir M. haei~~i~p~ihm 121. rkeloiiae" .21.jorruittrm" M. avirim complcs* M. abscessus Leprosy: numerous cutaneous manifestations M. Iepml~ (plaques, nodules, ulcers)

aImmunocompromised patients particularly at risk

quently contracted from the environment, particularly from water supplies. Those most likely to cause skin disease are: M. ulcerans, M. nzarinutn, M. fortuitutn Figure 2 Lupus vulgaris: chronic granulomatous lesion on and M. chelonae. Risk factors for cutaneous atypical the nose and lips. mycobacterial infection include inimunosuppression due to HIV infection, the extreme; of age, lymphoma, until recently been believed to be allergic reactions to leukemia or immunosuppressive therapy. M. leprae may tuberculosis. There is debate about these conditions of course cause a wide range of skin manifestations. and some authorities believe that conditions such These are not discussed here. as erythema induratum (Bazin's disease) and papulo- M. tnarinurn causes single slowly evolving nodules necrotic tuberculids are in fact manifestations of which occasionally ulcerate. They tend to occur at the sarcoidosis or similar disease processes [ 11. Erythema peripheries, as the organism prefers lower temperatures. nodosum-raised red painful lumps on the front of the Lesions may spread with associated lymphadenopathy lower leg commonly associated with primary tuber- and resemble sporotrichosis (Figure 1). It is contracted culosis-is still, however, believed to be an allergic in swimming pools and aquaria [3.4]. reaction to tuberculosis. 'Buruli' or 'Bairnsdale ulcer' is caused by M. ulcerans. Diagnosis of cutaneous tuberculosis requires demon- This lesion traditionally causes small self-limiting stration of the organism by smear, culture or PCR. ulcers with a widely undermined base which cause Confirmation is not always possible, as the numbers of debilitating contractions on healing (Figure 3). It is bacilli within the lesions are highly variable. Cutaneous only seen in tropical areas of the world, particularly manifestations of tuberculosis respond to standard anti- Australia and sub-Saharan Africa. It has lately been tuberculous chemotherapy. Multiresistant TB may reported that the virulence of this organism in some cause cutaneous disease [2], and culture should be areas has increased. The reason for this is unknown. obtained where possible. M. scrofulaceurn may cause skin involvement with discharging sinuses from abscesses fornling over CUTANEOUS MANIFESTATIONS OF caseating lymphadenopathy. In contrast to lympha- NON-TUBERCULOUS MYCOBACTERIA (TABLE 1) denopathy caused by M. tuberculosis, the chest X-ray is usually normal, the disease is unilateral, there is no Non-tuberculous mycobacterial infections are fre- history of TB contact, tuberculin testing is negative and 462 Clinical Microbiology and Infection, Volume 4 Number 8, August 1998

contrast, M.fortuitum and M.chelonae are very resistant to standard antituberculous drugs. Localized lesions may be excised. In more extensive lesions, combina- tions of first- and second-line antituberculous chemo- therapy are advised. A detailed schedule for diagnosis and treatment of disease caused by non-tuberculous mycobacteria has been published by the American Thoracic Society [8].

Robert Baker*, Alimuddin Zumla Centre for Infectious Diseases, University College London Medical School, Windeyer Building, 46 Cleveland Street, London WIP 6DB, UK

'Tel: f44 171 380 9311 Fax: +44 171 380 9311

MULTIPLE-CHOICE QUESTIONS

1. Cutaneous complications of M. tuberculosis include a) Lupus pernio True/False b) Tuberculosis miliaris cutis disseminata True/False c) Cutaneous amyloid True/False Figure 3 Huruli ulcer duc to hfycobacterirrm ulccrans d) Erythema nodosum True/False infection. e) Glanders True/False 2. Atypical mycobacteria that are likely to victims tend to come from higher socio-economic cause skin disease in the immuno- classes [5].M. fortuiturn and M. chelonae may also cause compromised include: skin abscesses, as may M. haemophilum in the immuno- a) M. auirrni complex True/False compromised [6]. M. avium complex occasionally b) iz1. tuberculosis True/False causes localized cutaneous infection in AIDS patients c) M. scrojiulaceurvr True/False [7].It should be remembered that patients with AIDS d) Ad. haennophilur~i True/False are particularly vulnerable to widespread disseminated e) M.ulcerans True/False inycobacterial disease, which is frequently fatal. All 3. Skin infections with the following may be systems may be involved and blood, bone marrow and treated with standard antituberculous fecal stains and cultures must be performed in patients chemotherapy alone: with cutaneous mycobacteriosis. a) Bairnsdale ulcer TrudFalse TREATMENT OF NON-TUBERCULOUS b) M. tuberculosis True/False MYCOBACTERIAL INFECTIONS c) M. triuiale True/False d) M. niarinum True/False Treatment of patients with non-tuberculous niyco- e) M. scrojiulaceum TrudFalse bacterial infections is often difficult and they should be referred for expert advice, particularly in the immuno- 4. The following are differential diagnoses of compromised. In vitro and in vivo sensitivities fre- mycobacterial skin infection: quently do not correlate. M. vnarinunz usually responds a) Sporotrichosis TrudFalse very well to chemotherapy (rifampicin and ethambutol), b) Cat scratch disease True/False which should be continued at least until the lesions c) Anisakiasis True/False have fully resolved. M. scrojiulaceum varies in its suscep- d) Krabbt disease (globoid cell tibility to antituberculous and other antibacterial leucodystrophy) True/False agents, such as sulfonamides and erythromycin. In e) Scrub typhus True/False Baker and Zumla: The cutaneous manifestations of rnycobacterial diseases 463

5. M. ulcerans aquariums: a source of Mycobacterium marinum infections a) Is confined to sub-Saharan Africa True/False resembling sporotrichosis. JAMA 1970; 21 1: 457-61. 4. Philpott JA, Woodborne AR, Philpott 0s. Swimming pool b) May cause severe and debilitating granuloma. A study of 290 cases. Arch Dermatol 1963; tendon contractures True/False 88: 158-62. c) May require skin grafting True/False 5. Wolinsky E. Non tuberculous mycobacteria and associated d) Tends to be less severe nowadays True/False diseases. Am Rev Respir Dis 1979; 119: 107-59. e) Is caused by the synergistic action 6. Holton J, Nye P, Miller R. Mytobacterium haemophilum of two separate organisms True/False infection in a patient with AIDS. J Infect 1991; 23(3): 303-6. Acknowledgments 7. Esteban J, Gorgolas M, Fernandez Guerrero ML, Soriano E Figure 2 was provided by Dr €? Mwaba and Figure 3 by Localized cutaneous infection caused by Mycobacterium aviurri Professor J. Stanford. coniplex in an AIDS patient. Clir: Exp Dermatol 1996; 21(3): 230-1. 8. American Thoracic Society. Diagnosis and treatment of References disease caused by non tuberculous inycobacteria. Am Rev 1. Beyt A, Ortbals DW, Santa Cruz DJ. Cutaneous myco- Respir Dis 1990; 142: 940-52. bacterioses: analysis of 34 cases with a new classification of the disease. Medicine 1981; 60: 95-109. Q1: a. False; b. True; c. False; d. True; e. False 2. Antinori S, Gahmberti L, Tadini GL, et al. Tuberculosis cutis daris disseminata due to multidrug resistant Mycobacterium Q2: All true. tuberculosis in AIDS patients. Eur J Clin Microbiol Infect Dis 43: a. False; b. True; c. False; d. True; e. False 1995; 14(10): 911-14. 44: a. True; b. True; c. False; d. False; e. False 3. Adams RM, Remington JS, Steinberg J. Tropical fish Q5: a. False; b. True; c. True; d. False; e. False