==== Front Ann Saudi MedAnn Saudi MedAnnals of Saudi Medicine0256-49470975-4466King Faisal Specialist Hospital and Research Centre 1768442510.5144/0256-4947.2007.298asm-4-298Case ReportErythema induratum: What is the role of Mycobacterium tuberculosis? Alothman Adel Al Qahtani Mohammed Al Khenaizan Sultan From the Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi ArabiaCorrespondence and reprint requests: Adel Alothman, MBBS, King Abdulaziz Medical City 1443, PO Box 22490, Riyadh 11426, Saudi Arabia, T: 012520088 ext 14189, F: 012520088 ext 14229, alothman84@hotmail.comJul-Aug 2007 27 4 298 300 01 11 2006 Copyright © 2007, Annals of Saudi Medicine2007This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. ==== Body Erythema induratum (EI) was first described by Bazin in 1861, who attributed the condition to tuberculosis (TB).1,2 In 1901, Whitfield hypothesized that there were two forms of EI, one of which was related to TB.3 EI is a tuberculid, characterized by chronic or recurrent tender subcutaneous nodules, which sometimes ulcerate. The lesions typically are located on the lower extremities of adult women.1,4,5 Most individuals with EI have a positive tuberculin skin test, but rarely have evidence of active TB.4,8 EI lesions appear histopathologically as a granulomatous lobular panniculitis and vasculitis, with the affected artery lying in the septum of subcutaneous fat.4,8–11 Several authors were able to demonstrate Mycobacterium tuberculosis DNA by polymerase chain reaction (PCR) in tissue biopsy from EI lesions, which leads to the belief among investigators that M. tuberculosis has a role in EI lesions.9–13 We report two cases of EI and their therapeutic response and review the literature on EI. CASES The first case was a 63-year-old Saudi female who presented with a 3-week history of painful left lower limb erythema. There was neither a history of TB nor a family history of TB. On examination, she was had a well-defined 3 × 6 cm indurated ulcer at the medial aspect of the left leg close to the heel. The erythrocyte sedimentation rate (ESR) before treatment was 120 mm/hr and the PPD test was positive. Biopsy showed a chronic, active ulcer associated with focal granulomatous changes, with the inflammation extending to the subcutaneous adipose tissue associated with fat necrosis and thrombotic occlusion of blood vessels. The biopsy result was consistent with EI. Culture for M. tuberculosis and PCR were negative. The patient was treated with anti-TB medications (isoniazid, rifampicin, pyrazinamide and ethambutol) for 2 months and then isoniazid and rifampicin for 4 months. During this period, she showed a dramatic clinical response with gradual decline in the ESR to 39 mm/hr. The second case was a 35-year-old Saudi female who presented with a one-month history of painful multiple erythemas in both lower limbs. There was no previous history of TB and no family history of TB. On examination she had 9 multiple indurated, painful nodules, variable in size, 7 lesions in the left lower limb and 2 lesions in the right lower limb (Figure 1). ESR was 112 mm/hr and the PPD skin test was positive. A biopsy for this patient showed lobular panniculaitis, with inflammatory changes seen in the subcutaneous fat and in the interface between the reticular dermis and subcutaneous fat, where there was prominent venulitis in the reticular dermis. In addition, granulomatous inflammation was identified in the panniculus and in the reticular dermis. The biopsy result was consistent with EI. M. tuberculosis culture and PCR were negative. She was treated with anti-TB medications (isoniazid, rifampicin, pyrazinamide and ethambutol) for 2 months and then isoniazid and rifampicin for 4 months. She had an excellent clinical response (Figure 2) with a decline in the ESR to 30 mm/hr. DISCUSSION EI was described initially by Bazin in 1861.1,2 Audry, however, challenged the hypothesis that EI has any relation with M. tuberculosis in 1898.14 Whitfield reached the conclusion that there are two forms of EI, one of which was related to M. tuberculosis, in 1901.1,3 Montgomery and colleagues described 72 patients with EI, and most of the patients (85%) were females. A PPD test done on 25 patients was positive in 84%.15 Many authors have shown that EI can respond successfully to anti-TB therapy.16–18 Degitz and colleagues demonstrated that M. tuberculosis DNA can be found in the EI lesion by the use of PCR, in 1993. They were able to demonstrate M. tuberculosis DNA in skin biopsies using PCR in 5 of 7 patients with EI.19 Several authors have shown that EI lesions can be associated with other types of active TB like tuberculous lymphadenitis,6,20 pulmonary tuberculosis,21 renal tuberculosis, 22 endometrial tuberculosis,23 and tuberculosis of the nasopharynx.24 A review of the medical literature shows that EI lesions can present as a primary lesion1,4,5,8,15,18,19 or a secondary skin disease to other active tuberculosis.20–24 Distler and colleagues reported a case with panniculitis for 30 years,25 and Ollert and colleagues reported two cases of chronic EI for 10 years.8 All of these cases have responded successfully to anti-TB therapy. Both of our cases who had chronic EI lesions diagnosed histologically have successfully responded to 6 months of anti-TB therapy. However, both of our cases did not have caseating granuloma on the histopathology of their skin biopsy and we were not able to diagnose a tuberculous origin of their lesions microbiologically. Also, M. tuberculosis DNA was negative on the PCR in both cases. Most of the published studies support the use of M. tuberculosis-DNA PCR on skin biopsy of EI lesions,9 but a few investigators have not found PCR to be a useful test in cutaneous TB.13 We believe that the recent molecular biology evidence that M. tuberculosis DNA is present in a majority of EI lesions together with the successful response to anti-TB therapy supports the hypothesis that most cases of EI are due to a paucibacillary M. tuberculosis-DNA infection of the skin. We recommend that EI patients be given a trial of anti-TB therapy (for example, isoniazid 300 mg by mouth once daily, rifampicin 600 mg by mouth once daily, pyrazinamide 1.5 g. by mouth once daily, and ethambutol 800 mg by mouth once daily for the first 2 months, then continue isoniazid and rifampicin for another 4 months) while waiting for M. tuberculosis-DNA PCR results, or evaluating the response to therapy in 4 weeks. Figure 1 Ulcerated erythema induratum on presentation. Figure 2 Healed erythema induratum after 6 weeks of therapy. ==== Refs REFERENCES 1 Shafran S Chui L Erythema Induratum as a form of active cutaneous tuberculosis: Case and Reviews Inf Dis Clin Pract 2000 9 33 36 2 Bazin E Lecons Theoretiques et cliniques sur la scrofule 2nd ed Paris Delahaye 1861 146 3 Whitfield A On the nature of the disease known as erythema induratum scrofulosorum Am J Med Sci 1901 122 828 34 4 Chang M Lawrence R Orlow S Erythema Induratum of Bazin in an infant Pediatr 1999 103 498 500 5 Rademaker M Lowe D Munro D Erythema Induratum (Bazin’s disease) J Am Acad Dermatol 1989 21 740 745 2808790 6 Shimizu A Takahashi A Nagishi I The close association of lymphadenitis tuberculosa and erythema induratum of Bazin in Japanese patients Dermatol 2003 207 426 27 7 Heinemann C Kaatz M Elsner P Erythema induratum of Bazin and Pancet;s disease - successful treatment with antitubercular drugs JEADV 2003 17 334 336 12702080 8 Ollert M Thomas P Korting H Erythema induratum of Bazin, Evidence of T-lymphocyte hyperresponsiveness to purified protein derivative of tuberculin: Report of two cases and treatment Arch Dermatol 1993 129 469 472 8466218 9 Baselga E Margall N Barnadas M Detection of Mycobacterium tuberculosis DNA in lobular granulomatous panniculitis (erythema induratum - nodular vasculitis) Arch Dermatol 1997 133 457 462 9126009 10 Jacinto S Nograles K Erythema induratum of Bazin: role of polymerase chain reaction in diagnosis Int J Dermatol 2003 421 380 381 11 Lee Y Lee S Lee J Erythema induratum with pulmonary tuberculosis: histopathologic features resembling true vasculitis Int J Dermatol 2001 40 193 196 11422524 12 Jordaan H Schneider J Abdulla E Nodular tuberculid: A Report of four patients Pedia Dermatol 2001 17 183 188 13 Tan S Tan B Goh C Detection of Mycobacterium tuberculosis DNA using polymerase chain reaction in cutaneous tuberculosis and tuberculids Int J Dermatol 1999 38 122 127 10192161 14 Audry C Etude de la lesion del erytheme indure (de Bazin) sur la notion du lymphatisme Ann Dermatol Syphilig (Paris) 1898 29 209 214 15 Montgomery H Oleary P Barker N Nodular vascular disease of the legs. 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