<<

Editorial Advances in the Diagnosis and Therapy of Mycobacterial Disease

Dirk M. Elston, MD

n this month’s issue of Cutis®, Johnson et al1 group of atypical mycobacteria. Patients with remind us of the importance of mycobacte- M chelonae or M abscessus tend to be older, more Irial skin infections. Mycobacterial diseases likely to be on immunosuppressive medications, and have reemerged as important skin infections, and present with multiple lesions. M fortuitum is more has increasing relevance for the der- likely to manifest as a solitary lesion, and patients matologist in the age of biologic therapy for inflam- are more likely to have had a prior invasive surgical matory skin disease. Reactivation of tuberculosis procedure at the infected site.10 Deep and extensive should be considered a risk with all tumor necrosis M fortuitum complex infections have been related factor (TNF) agents, though most reports are related to nail salon footbaths11; M abscessus infections to infliximab.2 has been reported have been related to treatments12; and in this setting.3 Reactivation has occurred even in M chelonae infection has followed liposculpture and the face of prophylaxis.4 Nontuberculous lipofilling procedures.13 mycobacterial disease also has been associated with ulcerans infections generally occur anti-TNF therapy.5 in Africa, but cases also have been reported in Mycobacterial infections are increasing in num- Mexico.14 is no longer common but ber worldwide. Factors contributing to the reemer- still occurs worldwide. gence of tuberculosis in the United States include a Although the typical histology of atypical myco- global increase in developing countries, an increase bacterial infection is that of granulomatous dermati- in the number of patients with human immunode- tis with stellate abscesses and sinus tracts, lichenoid ficiency virus (HIV) infection, and the emergence and granulomatous dermatitis has been noted in of multidrug-resistant tuberculosis.6 Mycobacterium Mycobacterium kansasii and M marinum infections.15 bovis is the causative agent of bovine tuberculosis A Fite stain should be prompted by clinical features and the importance of reservoirs in wild animal pop- suspicious for atypical mycobacterial infection, even ulations recently has been established.7 Although in the absence of deep granulomatous infiltrates Mycobacterium tuberculosis accounts for most infec- with neutrophilic abscesses. tions, recent outbreaks of human tuberculosis in the The diagnosis of mycobacterial disease has been United States also have been related to M bovis, and dependent on identifying the organism in smears or soft cheeses of Mexican origin have been implicated culture. DNA hybridization on nitrocellulose strips as a source of these infections.8 has been used to identify M tuberculosis complex infection typically occurs isolates to the species level and compares favorably with sporotrichoid nodules on an extremity after with polymerase chain reaction (PCR) techniques, exposure to water from a fish tank, swimming pool, biochemical tests, and susceptibility testing.16 A or brackish inlet. M marinum tenosynovitis can whole-blood interferon-g enzyme-linked immuno- mimic arthritic disease. Patients may develop exten- sorbent assay (QuantiFERON TB-2G [QFT-TB]; sive infection after steroid injections. Findings sug- Cellestis) has demonstrated promise in distinguish- gestive of M marinum tenosynovitis include a fish- or ing between active tuberculosis and nontuberculous water-associated injury, negative routine bacterial mycobacteriosis. This type of in vitro testing can be tissue cultures, and poor response to conventional used as a supplement to tuberculin skin testing.17 antibiotic treatment.9 Conventional and real-time PCR assays for detec- , , tion of DNA based on the and are the rapid growing antigen 85B-coding gene or the 85A-C intergenic region can result in detection rates of 100% in

From the Departments of Dermatology and Laboratory Medicine, patients with multibacillary disease and from 62.5% 18 Geisinger Medical Center, Danville, Pennsylvania. to 79.2% among those with paucibacillary disease. The author reports no conflict of interest. PCR assays may be negative when mycobacteria are

VOLUME 79, JANUARY 2007 17 Editorial

not visible in Fite-stained sections. Gene probes that mycobacterial infection, dermatologists would do target 16S ribosomal RNA and 16S ribosomal DNA well to remain familiar with the current diagnostic have proved useful in the diagnosis of smear negative and therapeutic options. mycobacterial disease.19 Interferon g release assays using tuberculosis-specific antigens have a sensitiv- References ity of 81% in HIV-infected tuberculosis patients.20 1. Johnson RP, Xia Y, Cho S, et al. Mycobacterium marinum This sort of assay may be useful in the setting of infection: a case report and review of the literature. Cutis. immunosuppression related to biologic therapy for 2007;79:33-36. psoriasis where skin testing is less reliable. Elevated 2. Moiton MP, Richez C, Dumoulin C, et al. Role of levels of soluble urokinase receptor in serum may be anti-tumour necrosis factor-alpha therapeutic agents a marker for persistent extrapulmonary mycobacte- in the emergence of infections. Clin Microbiol Infect. rial infection during therapy.21 2006;12:1151-1153. Skin testing has proved useful in the screen- 3. Stas P, D’Hoore A, Van Assche G, et al. Miliary tubercu- ing for nontuberculous mycobacterial infection in losis following infliximab therapy for Crohn disease: a case children. In a study of 180 children with chronic report and review of the literature. Acta Gastroenterol Belg. cervicofacial lymphadenitis, skin testing was done 2006;69:217-220. using antigens of M tuberculosis, Mycobacterium 4. Sichletidis L, Settas L, Spyratos D, et al. Tuberculosis in avium, M kansasii, and Mycobacterium scrofulaceum. patients receiving anti-TNF agents despite chemoprophy- These results compared identification by culture, laxis. Int J Tuberc Lung Dis. 2006;10:1127-1132. PCR, or both. One hundred twelve nontuberculous 5. Okubo H, Iwamoto M, Yoshio T, et al. Rapidly aggravated mycobacterial infections were identified (83 caused Mycobacterium avium infection in a patient with rheu- by M avium, 21 by Mycobacterium haemophilum, and matoid arthritis treated with infliximab. Mod Rheumatol. 8 by other species). Using a 5-mm cutoff for a posi- 2005;15:62-64. tive skin test, tuberculin skin testing demonstrated 6. De Backer AI, Mortele KJ, De Keulenaer BL, et al. a sensitivity and specificity of 70% and 98%, respec- Tuberculosis: epidemiology, manifestations, and the value tively. M avium sensitin, the best-performing skin of medical imaging in diagnosis. JBR-BTR. 2006;89: test, had positive and negative predictive values of 243-250. 98% and 90%, respectively.22 It should be noted that 7. Courtenay O, Reilly LA, Sweeney FP, et al. Is a response to therapy may be the ultimate indication in the environment important of tuberculous skin infection in patients with nega- for the persistence of bovine tuberculosis? Biol Lett. tive PCR, skin tests, and culture.23 2006;2:460-462. Minocycline, doxycycline, clarithromycin, or a 8. Harris NB, Payeur J, Bravo D, et al. Recovery of Mycobacterium combination of rifampicin and ethambutol hydro- bovis from soft fresh cheese originating from Mexico. Appl chloride may be used as initial empiric therapy for Environ Microbiol [serial online]. December 1, 2006. M marinum infections.24 Minocycline has been 9. Tsai HC, Lee SS, Wann SR, et al. Mycobacterium reported as successful even when a patient did not marinum tenosynovitis: three case reports and review of respond to doxycycline.25 the literature. Jpn J Infect Dis. 2006;59:337-340. Deep M marinum infections involving the hand 10. Uslan DZ, Kowalski TJ, Wengenack NL, et al. Skin and can be aggressive and result in permanent disability. soft tissue infections due to rapidly growing mycobacteria: Specialists in infectious disease and hand surgery comparison of clinical features, treatment, and susceptibility. should be consulted.26 Photodynamic therapy may Arch Dermatol. 2006;142:1287-1292. have some role in the treatment of M marinum infec- 11. Redbord KP, Shearer DA, Gloster H, et al. Atypical tions, though more data are needed.27 Mycobacterium furunculosis occurring after pedicures. Fluoroquinolones are relatively recent additions J Am Acad Dermatol. 2006;54:520-524. to the armamentarium against mycobacterial patho- 12. Song JY, Sohn JW, Jeong HW, et al. An outbreak of post- gens. Minimal inhibitory concentrations are not acupuncture cutaneous infection due to Mycobacterium always predictive of clinical response, and lack abscessus. BMC Infect Dis. 2006;6:6. of intracellular killing may contribute to lower 13. Giannella M, Pistella E, Perciaccante A, et al. Soft tissue in vivo activity of ciprofloxacin hydrochloride.28 infection caused by Mycobacterium chelonae following a Clarithromycin or azithromycin are preferred as liposculpture and lipofilling procedure. Ann Ital Med Int. initial therapy for M abscessus but should be supple- 2005;20:245-247. mented with other drugs such as sulfate to 14. Coloma JN, Navarrete-Franco G, Iribe P, et al. Ulcerative avoid emergence of resistance.29 cutaneous mycobacteriosis due to : As mycobacterial disease becomes more common report of two Mexican cases. Int J Lepr Other Mycobact Dis. and we use more biologic agents that predispose to 2005;73:5-12.

18 CUTIS® Editorial

15. S Breza T Jr, Magro CM. Lichenoid and granulomatous 22. Lindeboom JA, Kuijper EJ, Prins JM, et al. Tuberculin skin dermatitis associated with atypical Mycobacterium infec- testing is useful in the screening for nontuberculous myco- tions. J Cutan Pathol. 2006;33:512-515. bacterial cervicofacial lymphadenitis in children. Clin Infect 16. Gomez MP, Herrera-Leon L, Jimenez MS, et al. Comparison of Dis. 2006;43:1547-1551. GenoType((R)) MTBC with RFLP-PCR and multiplex PCR 23. Akoglu G, Karaduman A, Boztepe G, et al. A case of to identify Mycobacterium tuberculosis complex species. Eur J lupus vulgaris successfully treated with antituberculous Clin Microbiol Infect Dis [serial online]. December 5, 2006. therapy despite negative PCR and culture. Dermatology. 17. Kobashi Y, Obase Y, Fukuda M, et al. Clinical reevaluation 2005;211:290-292. of the QuantiFERON TB-2G test as a diagnostic method 24. Petrini B. Mycobacterium marinum: ubiquitous agent for differentiating active tuberculosis from nontuberculous of waterborne granulomatous skin infections. Eur J Clin mycobacteriosis. Clin Infect Dis. 2006;43:1540-1546. Microbiol Infect Dis [serial online]. September 19, 2006. 18. Martinez AN, Britto CF, Nery JA, et al. Evaluation 25. Cummins DL, Delacerda D, Tausk FA. Mycobacterium of real-time and conventional PCR targeting complex marinum with different responses to second-generation tet- 85 genes for detection of Mycobacterium leprae DNA in racyclines. Int J Dermatol. 2005;44:518-520. skin biopsy samples from patients diagnosed with . 26. Rajesh G, Ip WY, Chow SP, et al. Treating deep-seated J Clin Microbiol. 2006;44:3154-3159. Mycobacterium marinum infection in the hand: a report of 19. Kamal R, Dayal R, Katoch VM, et al. Analysis of gene three cases. Hand Surg. 2006;11:83-88. probes and gene amplification techniques for diagno- 27. Wiegell SR, Kongshoj B, Wulf HC. Mycobacterium marinum sis and monitoring of treatment in childhood leprosy. infection cured by photodynamic therapy. Arch Dermatol. Lepr Rev. 2006;77:141-146. 2006;142:1241-1242. 20. Tsiouris SJ, Coetzee D, Toro PL, et al. Sensitivity analy- 28. Shandil RK, Jayaram R, Kaur P, et al. Moxifloxacin, sis and potential uses of a novel gamma interferon ofloxacin, sparfloxacin, and ciprofloxacin against release assay for diagnosis of tuberculosis. J Clin Microbiol. Mycobacterium tuberculosis: evaluation of in vitro and 2006;44:2844-2850. pharmacodynamic indices that best predict in vivo 21. Ostrowski SR, Ravn P, Hoyer-Hansen G, et al. Elevated lev- efficacy. Antimicrob Agents Chemother [serial online]. els of soluble urokinase receptor in serum from mycobacte- December 4, 2006. ria infected patients: still looking for a marker of treatment 29. Petrini B. Mycobacterium abscessus: an emerging rapid- efficacy. Scand J Infect Dis. 2006;38:1028-1032. growing potential pathogen. APMIS. 2006;114:319-328.

VOLUME 79, JANUARY 2007 19