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Painless Round Ulcers on the Leg

The Diagnosis: Cutaneous Tuberculosis 

The patient's medical history was notable for bone tuberculosis (TB) treated in childhood. Skin biopsy revealed neutrophilic infiltrates with necrosis without granulomas. A real-time polymerase chain reaction test detected Mycobacterium tuberculosis complex in the skin fragment, which was confirmed by culture of the biopsy specimen using a liquid growth medium that grew M tuberculosis. Tuberculotic foci were not present on the lungs, gastrointestinal tract, kidneys, and bones by radiologic, microbiologic, and ultrasonographic investigations. The patient was started on 4 antituberculotic drugs--isoniazid 300 mg, rifampicin 600 mg, ethambutol 1200 mg, pyrazinamide 1500 mg--once daily for 2 months followed by isoniazid 300 mg and rifampicin 600 mg once daily for another 4 months with resolution of the skin lesions. 

Cutaneous TB is an infectious disease caused by M tuberculosis and accounts for only 1.5% of extrapulmonary TB cases.1,2 Similar to other forms of TB, a resurgence of cutaneous TB has been noted in parts of the world where human immunodeficiency virus infection is prevalent and remains to be one of the most elusive and more difficult diseases to diagnose.3 Thought to be a predominantly occupational disease, it is being encountered more frequently in healthy individuals where the source of infection remains unidentified in most cases.4 The clinical types depend on the method of infection, virulence of the bacillus, immune status of the host, and presence or absence of host sensitization to M tuberculosis.2 The route of infection is used to classify cutaneous mycobacteriosis.5 Inoculation from an exogenous source can produce TB verrucosa cutis in individuals who have previously been sensitized to M tuberculosis or tuberculous chancre in individuals without prior exposure to the bacterium.4 Cutaneous TB resulting from direct spread to the skin from an underlying contiguous structure in most cases spreads from lymph nodes and bone (scrofuloderma). Immunosuppressed patients with advanced TB of the lung, gastrointestinal tract, or the genitourinary tract may present with periorificial TB.4 Dissemination to the skin caused by hematogenous spread can occur in the form of lupus vulgaris, miliary TB, or metastatic tuberculous abscesses (gummas).4,5 A fourth category--cutaneous TB from paradoxical expansion--also was proposed. Paradoxical expansion is defined as the transient expansion of a preexisting lesion or the appearance of new lesions during appropriate anti-TB therapy.

Although histopathology and protein chain reaction tests are useful, the gold standard for diagnosis is still the isolation of M tuberculosis on culture.3,6 Treatment regimens of cutaneous TB are similar to those of pulmonary TB, with a 4-agent regimen given for 2 months followed by a 2-drug regimen for the next 4 months.1,7 The differential diagnosis of leg ulcers includes stasis ulcer, necrobiotic xanthogranuloma, pyoderma gangrenosum, and squamous cell carcinoma, among others. Cutaneous biopsy, microbiological culture, and a high degree of suspicion are fundamental for the final diagnosis. Cutaneous TB should be suspected in immunocompetent as well as in immunosuppressed patients who present with ulcerated lesions that do not respond to antibacterial treatment.

References
  1. Karoney MJ, Kaumbuki EK, Koech MK, et al. Primary cutaneous tuberculosis in a 27-year-old medical intern from needle-stick injury: a case report. Clin Case Rep. 2015;3:39-42. 
  2. Spelta K, Diniz LM. Cutaneous tuberculosis: a 26-year retrospective study in an endemic area of tuberculosis, Vitória, Espírito Santo, Brazil. Rev Inst Med Trop Sao Paulo. 2016;58:49. 
  3. Sahin N, Aydin NE, Senol M, et al. Longstanding skin ulcers due to Mycobacterium tuberculosis in a healthy man. Trop Biomed. 2010;27:120-124. 
  4. Semaan R, Traboulsi R, Kanj S. Primary Mycobacterium tuberculosis complex cutaneous infection: report of two cases and literature review. Int J Infect Dis. 2008;12:472-477. 
  5. Ram R, Uppin S, Swarnalatha G, et al. Isolated skin ulcers due to Mycobacterium tuberculosis in a renal allograft recipient. Nat Clin Pract Nephrol. 2007;3:688-693. 
  6. Bravo FG, Gotuzzo E. Cutaneous tuberculosis. Clin Dermatol. 2007;25:173-180. 
  7. Handog EB, Gabriel TG, Pineda RT. Management of cutaneous tuberculosis. Dermatol Ther. 2008;21:154-161.
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From the Department of Dermatology and Venereology, Centro Hospitalar São João, EPE Porto, Portugal. Dr. Moreira also is from the University of Porto.

The authors report no conflict of interest.

Correspondence: Miguel Costa-Silva, MD, Department of Dermatology and Venereology, Centro Hospitalar São João, 4200-319 Porto, Portugal (miguelcostaesilva.dermato@gmail.com).

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From the Department of Dermatology and Venereology, Centro Hospitalar São João, EPE Porto, Portugal. Dr. Moreira also is from the University of Porto.

The authors report no conflict of interest.

Correspondence: Miguel Costa-Silva, MD, Department of Dermatology and Venereology, Centro Hospitalar São João, 4200-319 Porto, Portugal (miguelcostaesilva.dermato@gmail.com).

Author and Disclosure Information

From the Department of Dermatology and Venereology, Centro Hospitalar São João, EPE Porto, Portugal. Dr. Moreira also is from the University of Porto.

The authors report no conflict of interest.

Correspondence: Miguel Costa-Silva, MD, Department of Dermatology and Venereology, Centro Hospitalar São João, 4200-319 Porto, Portugal (miguelcostaesilva.dermato@gmail.com).

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The Diagnosis: Cutaneous Tuberculosis 

The patient's medical history was notable for bone tuberculosis (TB) treated in childhood. Skin biopsy revealed neutrophilic infiltrates with necrosis without granulomas. A real-time polymerase chain reaction test detected Mycobacterium tuberculosis complex in the skin fragment, which was confirmed by culture of the biopsy specimen using a liquid growth medium that grew M tuberculosis. Tuberculotic foci were not present on the lungs, gastrointestinal tract, kidneys, and bones by radiologic, microbiologic, and ultrasonographic investigations. The patient was started on 4 antituberculotic drugs--isoniazid 300 mg, rifampicin 600 mg, ethambutol 1200 mg, pyrazinamide 1500 mg--once daily for 2 months followed by isoniazid 300 mg and rifampicin 600 mg once daily for another 4 months with resolution of the skin lesions. 

Cutaneous TB is an infectious disease caused by M tuberculosis and accounts for only 1.5% of extrapulmonary TB cases.1,2 Similar to other forms of TB, a resurgence of cutaneous TB has been noted in parts of the world where human immunodeficiency virus infection is prevalent and remains to be one of the most elusive and more difficult diseases to diagnose.3 Thought to be a predominantly occupational disease, it is being encountered more frequently in healthy individuals where the source of infection remains unidentified in most cases.4 The clinical types depend on the method of infection, virulence of the bacillus, immune status of the host, and presence or absence of host sensitization to M tuberculosis.2 The route of infection is used to classify cutaneous mycobacteriosis.5 Inoculation from an exogenous source can produce TB verrucosa cutis in individuals who have previously been sensitized to M tuberculosis or tuberculous chancre in individuals without prior exposure to the bacterium.4 Cutaneous TB resulting from direct spread to the skin from an underlying contiguous structure in most cases spreads from lymph nodes and bone (scrofuloderma). Immunosuppressed patients with advanced TB of the lung, gastrointestinal tract, or the genitourinary tract may present with periorificial TB.4 Dissemination to the skin caused by hematogenous spread can occur in the form of lupus vulgaris, miliary TB, or metastatic tuberculous abscesses (gummas).4,5 A fourth category--cutaneous TB from paradoxical expansion--also was proposed. Paradoxical expansion is defined as the transient expansion of a preexisting lesion or the appearance of new lesions during appropriate anti-TB therapy.

Although histopathology and protein chain reaction tests are useful, the gold standard for diagnosis is still the isolation of M tuberculosis on culture.3,6 Treatment regimens of cutaneous TB are similar to those of pulmonary TB, with a 4-agent regimen given for 2 months followed by a 2-drug regimen for the next 4 months.1,7 The differential diagnosis of leg ulcers includes stasis ulcer, necrobiotic xanthogranuloma, pyoderma gangrenosum, and squamous cell carcinoma, among others. Cutaneous biopsy, microbiological culture, and a high degree of suspicion are fundamental for the final diagnosis. Cutaneous TB should be suspected in immunocompetent as well as in immunosuppressed patients who present with ulcerated lesions that do not respond to antibacterial treatment.

The Diagnosis: Cutaneous Tuberculosis 

The patient's medical history was notable for bone tuberculosis (TB) treated in childhood. Skin biopsy revealed neutrophilic infiltrates with necrosis without granulomas. A real-time polymerase chain reaction test detected Mycobacterium tuberculosis complex in the skin fragment, which was confirmed by culture of the biopsy specimen using a liquid growth medium that grew M tuberculosis. Tuberculotic foci were not present on the lungs, gastrointestinal tract, kidneys, and bones by radiologic, microbiologic, and ultrasonographic investigations. The patient was started on 4 antituberculotic drugs--isoniazid 300 mg, rifampicin 600 mg, ethambutol 1200 mg, pyrazinamide 1500 mg--once daily for 2 months followed by isoniazid 300 mg and rifampicin 600 mg once daily for another 4 months with resolution of the skin lesions. 

Cutaneous TB is an infectious disease caused by M tuberculosis and accounts for only 1.5% of extrapulmonary TB cases.1,2 Similar to other forms of TB, a resurgence of cutaneous TB has been noted in parts of the world where human immunodeficiency virus infection is prevalent and remains to be one of the most elusive and more difficult diseases to diagnose.3 Thought to be a predominantly occupational disease, it is being encountered more frequently in healthy individuals where the source of infection remains unidentified in most cases.4 The clinical types depend on the method of infection, virulence of the bacillus, immune status of the host, and presence or absence of host sensitization to M tuberculosis.2 The route of infection is used to classify cutaneous mycobacteriosis.5 Inoculation from an exogenous source can produce TB verrucosa cutis in individuals who have previously been sensitized to M tuberculosis or tuberculous chancre in individuals without prior exposure to the bacterium.4 Cutaneous TB resulting from direct spread to the skin from an underlying contiguous structure in most cases spreads from lymph nodes and bone (scrofuloderma). Immunosuppressed patients with advanced TB of the lung, gastrointestinal tract, or the genitourinary tract may present with periorificial TB.4 Dissemination to the skin caused by hematogenous spread can occur in the form of lupus vulgaris, miliary TB, or metastatic tuberculous abscesses (gummas).4,5 A fourth category--cutaneous TB from paradoxical expansion--also was proposed. Paradoxical expansion is defined as the transient expansion of a preexisting lesion or the appearance of new lesions during appropriate anti-TB therapy.

Although histopathology and protein chain reaction tests are useful, the gold standard for diagnosis is still the isolation of M tuberculosis on culture.3,6 Treatment regimens of cutaneous TB are similar to those of pulmonary TB, with a 4-agent regimen given for 2 months followed by a 2-drug regimen for the next 4 months.1,7 The differential diagnosis of leg ulcers includes stasis ulcer, necrobiotic xanthogranuloma, pyoderma gangrenosum, and squamous cell carcinoma, among others. Cutaneous biopsy, microbiological culture, and a high degree of suspicion are fundamental for the final diagnosis. Cutaneous TB should be suspected in immunocompetent as well as in immunosuppressed patients who present with ulcerated lesions that do not respond to antibacterial treatment.

References
  1. Karoney MJ, Kaumbuki EK, Koech MK, et al. Primary cutaneous tuberculosis in a 27-year-old medical intern from needle-stick injury: a case report. Clin Case Rep. 2015;3:39-42. 
  2. Spelta K, Diniz LM. Cutaneous tuberculosis: a 26-year retrospective study in an endemic area of tuberculosis, Vitória, Espírito Santo, Brazil. Rev Inst Med Trop Sao Paulo. 2016;58:49. 
  3. Sahin N, Aydin NE, Senol M, et al. Longstanding skin ulcers due to Mycobacterium tuberculosis in a healthy man. Trop Biomed. 2010;27:120-124. 
  4. Semaan R, Traboulsi R, Kanj S. Primary Mycobacterium tuberculosis complex cutaneous infection: report of two cases and literature review. Int J Infect Dis. 2008;12:472-477. 
  5. Ram R, Uppin S, Swarnalatha G, et al. Isolated skin ulcers due to Mycobacterium tuberculosis in a renal allograft recipient. Nat Clin Pract Nephrol. 2007;3:688-693. 
  6. Bravo FG, Gotuzzo E. Cutaneous tuberculosis. Clin Dermatol. 2007;25:173-180. 
  7. Handog EB, Gabriel TG, Pineda RT. Management of cutaneous tuberculosis. Dermatol Ther. 2008;21:154-161.
References
  1. Karoney MJ, Kaumbuki EK, Koech MK, et al. Primary cutaneous tuberculosis in a 27-year-old medical intern from needle-stick injury: a case report. Clin Case Rep. 2015;3:39-42. 
  2. Spelta K, Diniz LM. Cutaneous tuberculosis: a 26-year retrospective study in an endemic area of tuberculosis, Vitória, Espírito Santo, Brazil. Rev Inst Med Trop Sao Paulo. 2016;58:49. 
  3. Sahin N, Aydin NE, Senol M, et al. Longstanding skin ulcers due to Mycobacterium tuberculosis in a healthy man. Trop Biomed. 2010;27:120-124. 
  4. Semaan R, Traboulsi R, Kanj S. Primary Mycobacterium tuberculosis complex cutaneous infection: report of two cases and literature review. Int J Infect Dis. 2008;12:472-477. 
  5. Ram R, Uppin S, Swarnalatha G, et al. Isolated skin ulcers due to Mycobacterium tuberculosis in a renal allograft recipient. Nat Clin Pract Nephrol. 2007;3:688-693. 
  6. Bravo FG, Gotuzzo E. Cutaneous tuberculosis. Clin Dermatol. 2007;25:173-180. 
  7. Handog EB, Gabriel TG, Pineda RT. Management of cutaneous tuberculosis. Dermatol Ther. 2008;21:154-161.
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A 78-year-old man was referred to our clinic for evaluation of 2 painless round ulcers with an undermined edge and purulent discharge on the left posterior leg of 2 months' duration. The ulcers had appeared following a presumed trauma. He had received repeated courses of oral antibiotics and antifungals without improvement. No regional lymphadenopathy could be detected. Biochemical analyses were within reference range. Human immunodeficiency virus 1 and 2, hepatitis B and C antibodies, and a VDRL test were all negative. 

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