|IMAGES IN RHEUMATOLOGY
|Ahead of print publication
Multidrug-resistant primary cutaneous tuberculosis: A rare cause of chronic nonhealing leg ulcer in systemic lupus erythematosus
Pawan Goel1, Prabhat Kumar1, Shipra Agarwal2
1 Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
Department of Medicine, Third Floor, Teaching Block, All India Institute of Medical Sciences, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
Keywords: Lupus nephritis, steroid, vasculitis
|How to cite this URL:|
Goel P, Kumar P, Agarwal S. Multidrug-resistant primary cutaneous tuberculosis: A rare cause of chronic nonhealing leg ulcer in systemic lupus erythematosus. Indian J Rheumatol [Epub ahead of print] [cited 2019 Jun 26]. Available from: http://www.indianjrheumatol.com/preprintarticle.asp?id=259904
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that can virtually affect any organ system of the body. Chronic skin ulcerations in SLE are both diagnostic and therapeutic challenge for a clinician. These ulcerations are generally secondary to vasculitis, microthrombotic diseases, or venous insufficiency. Vasculitis-related ulcerations are more common and are often treated with steroids and immunosuppressants. The long-term use of immunosuppressants and impaired immune functions often make them vulnerable to infections. Chronic nontuberculous mycobacterium (NTM) infection is a rare cause of chronic skin ulceration in SLE and can mimic lupus vasculitis. However, to the best of our knowledge, cutaneous Mycobacterium tuberculosis (MTB) infection causing chronic leg ulceration in SLE has not been reported yet. Herein, we present a case of chronic nonhealing leg ulcer due to multidrug-resistant (MDR) MTB infection in a patient of lupus nephritis which was successfully treated with antituberculous drugs.
A 35-year-old female presented with complaints of nonhealing painless ulcer over posterior aspect of the right thigh for the last 4 months. The ulcer started as a papule after trivial trauma and gradually progressed to the present size. She also received multiple courses of intravenous and oral antibiotics along with local debridement of the ulcer in the last 6 months. Nine months back, she was admitted with history of polyarthralgia and pedal edema for a month. Investigations done at that time revealed raised serum creatinine levels, nephrotic range proteinuria, positive direct Coomb's test, low complement levels with positive antinuclear antibody, and antidouble-stranded DNA antibody. A diagnosis of SLE with Class IV lupus nephritis was made after renal biopsy, for which she received high doses of steroid along with cyclophosphamide injection as per NIH regimen. Subsequently, she was started on oral mycophenolate mofetil (2 g/day), and moderate dose of oral prednisolone (30 mg/day) was continued in view of partial remission. There was no history of cough, significant weight loss, or TB in the past. On examination, there was a large deep ulcer measuring 15 cm × 6 cm with undermined edges, and granulation tissue covered base on the posterior aspect of the right thigh which was extending beyond popliteal fossa [Figure 1]. Due to contracture, the range of movement around the right knee joint was restricted. All peripheral pulses were palpable, and no significant lymphadenopathy was noted. Blood investigations revealed increase in acute-phase reactants with normal blood glucose levels and renal function tests. Urine analysis showed proteinuria of 2 g/day; however, complement levels were normal. Furthermore, workup for antiphospholipid syndrome and cryoglobulinemia was negative. Arterial and venous Doppler study of the lower limb was normal. X-ray of the lower limb did not show any evidence of osteomyelitis. Skin punch biopsy done from ulcer margin showed granulomatous inflammation with multiple acid-fast bacilli [Figure 2]. GeneXpert for MTB was positive and showed resistance to rifampicin (RIF). MTB culture and Mantoux test were negative. Sputum and urine examination for MTB was negative. A contrast-enhanced computed topography of the abdomen and chest done to look for disseminated TB was normal.
A diagnosis of MDR cutaneous TB (CTB) was made. She was started on intensive phase regimen of MDR-TB consisting of kanamycin, levofloxacin, ethionamide, cycloserine, pyrazinamide, and ethambutol for 6 months followed by continuation phase with levofloxacin, ethionamide, cycloserine, and ethambutol. Furthermore, the dose of mycophenolate mofetil was increased to 3 g/day, and oral prednisolone was subsequently tapered. She tolerated these drugs well, and no major adverse effects were noted in the first 6 months of treatment. Her ulcer healed completely within 6 months with residual scar and contracture [Figure 3]. At present, her lupus nephritis is in complete remission, and she is on maintenance doses of mycophenolate mofetil and continuation phase of MDR-TB treatment.
|Figure 3: Complete resolution of ulcer within 6 months of multidrug-resistant tuberculosis treatment|
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| Discussion|| |
Leg ulcerations in SLE are not uncommon and are due to variety of factors. Vasculitis is the most common cause of such ulcer followed by venous insufficiency, thrombosis of vessels, and lupus profundus. Atypical mycobacterium infection can rarely cause skin ulcerations in SLE patients; however, we could not find any literature on chronic ulcerations secondary to MTB infection of skin. CTB comprises only 1–2% of all extra pulmonary TB, and it can be acquired either by exogenous or endogenous route. Exogenous infection results from direct entry of MTB bacilli into the skin whereas endogenous infection is secondary to dissemination of bacilli from a primary focus. Primary CTB is rare and develops after exogenous inoculation of MTB in the skin after local injury, surgical procedure, or tattooing. Individuals not previously sensitized or having poor immunity to mycobacterium develop tuberculous chancre, which later progresses to form ulcer. Those previously infected with MTB or having strong immunity develop TB verrucosa cutis after exogenous inoculation.
The diagnosis is made on biopsy which demonstrates granuloma with acid-fast bacilli. Mycobacterial culture remains gold standard for diagnosis, but yield is poor in CTB. The GeneXpert MTB/RIF assay helps in rapid identification of rifampicin-resistant MTB which is considered a reliable proxy for MDR-TB., The delay in diagnosis often leads to multiple courses of antibiotics in these patients. Primary CTB is treated like pulmonary TB with antituberculous drugs.
SLE patients are more susceptible to mycobacterium infections due to abnormalities of immune system and chronic immunosuppressive therapy. Extrapulmonary TB in the form of CTB has been described earlier; however, the presentation was commonly in the form of subcutaneous nodules. Chronic NTM can also rarely cause chronic ulcers in SLE patients. In the present case, the MTB bacilli were probably inoculated during traumatic injury, and poor immune status of the patient led to ulcer formation. Furthermore, it was challenging to treat this patient of Class IV lupus nephritis with nephrotoxic drug like kanamycin.
To conclude, it is imperative for a clinician to consider infection as one of the differentials while managing chronic nonhealing ulcer in SLE patients.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Goslen JB. Autoimmune ulceration of the leg. Clin Dermatol 1990;8:92-117.
Petri M. Infection in systemic lupus erythematosus. Rheum Dis Clin North Am 1998;24:423-56.
Mok MY, Wong SS, Chan TM, Fong DY, Wong WS, Lau CS. Non-tuberculous mycobacterial infection in patients with systemic lupus erythematosus. Rheumatology (Oxford) 2007;46:280-4.
Bravo FG, Gotuzzo E. Cutaneous tuberculosis. Clin Dermatol 2007;25:173-80.
Lai-Cheong JE, Perez A, Tang V, Martinez A, Hill V, Menagé Hdu P. Cutaneous manifestations of tuberculosis. Clin Exp Dermatol 2007;32:461-6.
Wong HW, Tay YK, Sim CS. Papular eruption on a tattoo: A case of primary inoculation tuberculosis. Australas J Dermatol 2005;46:84-7.
Santos JB, Figueiredo AR, Ferraz CE, Oliveira MH, Silva PG, Medeiros VL. Cutaneous tuberculosis: Epidemiologic, etiopathogenic and clinical aspects – Part I. An Bras Dermatol 2014;89:219-28.
van Zyl L, du Plessis J, Viljoen J. Cutaneous tuberculosis overview and current treatment regimens. Tuberculosis (Edinb) 2015;95:629-38.
Zeka AN, Tasbakan S, Cavusoglu C. Evaluation of the geneXpert MTB/RIF assay for rapid diagnosis of tuberculosis and detection of rifampin resistance in pulmonary and extrapulmonary specimens. J Clin Microbiol 2011;49:4138-41.
World Health Organization. Policy Statement. Automated Real-Time Nucleic acid Amplification Technology for Rapid and Simultaneous Detection of Tuberculosis and Rifampicin Resistance: Xpert MTB/RIF System. Geneva: World Health Organization; 2011.
Hou CL, Tsai YC, Chen LC, Huang JL. Tuberculosis infection in patients with systemic lupus erythematosus: Pulmonary and extra-pulmonary infection compared. Clin Rheumatol 2008;27:557-63.
[Figure 1], [Figure 2], [Figure 3]