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Multiple Skin Colored Nodules on Both Legs in Patient with Positive QuantiferonⓇ-TB Gold Test

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A Case of Nodular Tuberculid pISSN 1013-9087ㆍeISSN 2005-3894 Ann Dermatol Vol. 29, No. 1, 2017 https://doi.org/10.5021/ad.2017.29.1.95 CASE REPORT Multiple Skin Colored Nodules on both Legs in Patient with Positive QuantiFERONⓇ-TB Gold Test Mi Soo Choi, Seung Phil Hong, Byung Cheol Park, Myung Hwa Kim Department of Dermatology, Dankook University Medical College, Cheonan, Korea Nodular tuberculid (NT) was originally described by Jordaan INTRODUCTION et al. in 2000 in 4 patients from South Africa. It appeared as nodules on the legs; the pathologic changes were situated in Tuberculosis (TB) remains one of the world’s most im- the deep dermis and adjacent subcutaneous fat. A 34-year-old portant communicable diseases. The number of TB cases woman visited our hospital with subcutaneous skin-colored is slowly declining year by year, but in 2013, according to or slightly erythematous round to oval nodules. Skin biopsies a report published in 2014, an estimated 9.0 million peo- revealed granulomatous inflammation at the dermo-sub- ple developed TB and 1.5 million died from the disease1. cutaneous junction with vasculitis. Chest X-ray, tuberculosus The prevalence and mortality of TB in Korea are 146 per (TB)-polymerase chain reaction and TB culture of the skin 100,000 and 5.4 per 100,000, respectively, which repre- specimen were normal. A QuantiFERONⓇ-TB Gold test sent the greatest prevalence and mortality among OECD (QUIAGEN, Germany) was positive, which suggested a diag- countries2. nosis of latent TB infection. The patient was treated with an- Cutaneous TB incidence parallels that of pulmonary TB. ti-TB medication and her condition has not recurred. Herein, The cutaneous lesions of Mycobacterium tuberculosis we report a case of a patient with latent TB diagnosed by a (MTB) infection have a variety of manifestations. Tuberculids positive QuantiFERONⓇ-TB Gold test whose skin lesions are recurrent skin or mucous membrane lesions in which had the clinical and histopathologic features of NT. (Ann tuberculous bacillus is absent; they are caused by hyper- Dermatol 29(1) 95∼99, 2017) sensitivity to MTB that spreads hematogenously from dis- tant extracutaneous foci. Nodular tuberculid (NT) was -Keywords- identified as a form of tuberculid by Jordaan et al.3 in Nodular tuberculid, QuantiFERONⓇ-TB Gold test, Tuberculid 2000. NT presents as red to bluish nodules without ul- ceration. Its main pathologic feature is granulomatous in- flammation at the dermo-subcutaneous junction. To diagnose TB infection in cases with tuberculids, tuber- culin skin tests, TB- polymerase chain reaction (PCR), QuantiFERONⓇ-TB Gold test (QUIAGEN, Duesseldorf, Germany), and T SPOT-TB tests are used. The Quanti- Received April 7, 2016, Revised August 16, 2016, Accepted for publication Ⓡ FERON -TB Gold test can diagnose latent TB infection. August 17, 2016 Corresponding author: Myung Hwa Kim, Department of Dermatology, MTB antigen stimulates T cells, which produce interferon- Ⓡ Dankook University Medical College, 201 Manghyang-ro, Dongnam-gu, γ (INF-γ), and the QuantiFERON -TB Gold test meas- Cheonan 31116, Korea. Tel: 82-41-550-6485, Fax: 82-41-552-7541, E-mail: ures the amount of INF-γ. The QuantiFERONⓇ-TB Gold misu2532@ naver.com test does not have a booster effect, and is less influenced This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. by the effects of previous bacille Clmette-Guerin (BCG) org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, vaccination, resulting in a lower false negative rate than distribution, and reproduction in any medium, provided the original work other tuberculin tests. is properly cited. We experienced a rare case of female patient with NT, in Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology whom latent TB infection was confirmed by a Quanti- Vol. 29, No. 1, 2017 95 MS Choi, et al FERONⓇ-TB Gold test. changes were mainly confined to the dermo-subcutaneous junction (Fig. 2∼4). Diastase-treated periodic acid-Schiff CASE REPORT (PAS) stain was negative and Ziehl-Neelsen stain failed to reveal acid-fast bacilli. Acid fast bacilli (AFB) culture and A 34-year-old woman had 7-month history of recurrent TB-PCR of skin tissue samples were negative for MTB. Her skin eruption on both lower extremities and the buttocks. husband had a history of incomplete treatment for pulmo- The lesions consisted of multiple tender subcutaneous nary TB, but the patient did not have a history of TB or as- skin-colored or slightly erythematous round to oval nodules. sociated symptoms such as chills, fever, cough, or night The lesions did not show any ulcerations or scars (Fig. 1). sweats. On physical examination, there were no enlarged The patient had no history of trauma, insect bites, or top- lymph nodes. Also, findings on a chest radiograph were ical use of drugs or cosmetics. Skin biopsy showed dermal normal. Her hemoglobin level was 10.8 g/dl, C-reactive necrosis and remarkable fat necrosis with lobular panni- protein was 1.36 mg/dl, and erythrocyte sedimentation culitis. Vasculitis was present in the small- to medium-sized rate was 46 mm/hr; other laboratory findings were within vessels. Diffuse infiltration of foamy histiocytes and mixed normal limits. However, a QuantiFERONⓇ-TB Gold test cell inflammation were also observed. The pathologic Fig. 3. Dense inflammatory cell infiltration around the vessels. Multinucleated giant cells, eosinophils, lymphocytes, foamy histiocytes, and neutrophils are evident (H&E, ×200). Fig. 1. Multiple tender skin-colored to slightly erythematous round to oval subcutaneous nodules. Fig. 2. Granulomatous inflammation at the dermo-subcutaneous Fig. 4. Caseous necrosis in the superficial subcutaneous layer junction (H&E, ×40). (H&E, ×100). 96 Ann Dermatol A Case of Nodular Tuberculid was positive, so a diagnosis of latent TB infection was fulosorum (LS) are included in this “tuberculids” group, made. The clinical and pathologic findings of our case are classically6. in accordance with tuberculid. We confirmed the diagnosis PNT is a symmetric eruption of red papules. The papules of NT. The patient was treated with isoniazid (300 of PNT show necrosis and become crusted. The skin le- mg/day), ethambutol (800 mg/day), and rifampicin (600 sions of PNT sometimes show spontaneous healing, asso- mg/day). All skin lesions had disappeared 3 months after ciated with scars. PNT usually occurs in the acral areas anti-TB treatment and she has experienced no recurrence. and extensor surfaces of the extremities, buttocks, and lower trunk3,6,7. The histopathology of PNT shows leuko- DISCUSSION cytoclastic and lymphohistiocytic vasculitis with wedge-shap- ed necrosis in the papillary dermis. Necrosis of the papil- Cutaneous lesions associated with MTB infection occur lary dermis extends into the epidermis, but caseous ne- because of direct inoculation of the skin from an exoge- crosis is absent3. nous source, autoinoculation, or hematogenous spread. EIB is a nodular subcutaneous eruption. The lesions of EIB Tuberculids are cutaneous hypersensitivity reactions to are characterized by tender, recurrent, erythematous, ul- MTB from distant extracutaneous foci of infection resulting cerating skin eruption on the lower extremities, and are from hematogenous spread. Tuberculids are recurrent skin most often found in young women. When EIB heals, it or mucous membrane lesions in which tuberculous ba- leaves an atrophic scar. The histologic features of EIB in- cillus is absent. The pathogenesis of tuberculids is the con- clude diffuse involvement of subcutaneous fat, vasculitis sequence of heightened T-cell-mediated immunity to MTB of small vessels, extensive necrosis, and granulomatous in- antigens from an extracutaneous focus in a patient with a flammation3. moderate or high degree of immunity against MTB. LS is characterized by uncommon lichenoid eruption that The characteristics of tuberculids consist of a positive tu- is caused by hematogenous spread of mycobacteria in an berculin test, internal tuberculous involvement, absence individual sensitive to MTB6. The lesions of LS are often of bacillus on mycobacterial cultures or stains of skin found on the trunk, mostly in children and adolescents. specimens, response to anti-TB medications, and specific- Asymptomatic, flat-topped yellowish or pink, firm, fol- ity in the context of TB4. Although acid-fast stain or culture licular small lichenoid papules occur in groups, some- of the skin lesion is negative, PCR can demonstrate MTB times with scales. Skin eruptions of LS resolve sponta- DNA in the biopsy lesion5. Papulonecrotic tuberculid neously without scarring. The histopathologic features of (PNT), erythema induratum of Bazin (EIB), and lichen scro- LS can be summarized by lymphohistiocytic to gran- Table 1. Summary of previously reported nodular tuberculid cases including this case QuantiFERONⓇ- No. Sex/age Clinical features Underlying disease Tuberculin test (skin) TB-PCR TB Gold test 1 F/19 mo Numerous crusted papules and Pulmonary TB >20 mm Not done Not done reddish nodules on limbs and ears 2 F/12 yr Bluish nodules on the lower limbs Pulmonary TB >20 mm Not done Not done 3 F/17 yr Nonulcerated purplish nodules Not evident >20 mm Not done Not done 4 F/5 yr Bluish nodules on the lower limbs Not evident >20 mm Not done Not done 5 F/26 yr Tender and red skin lesions→ Pulmonary TB, HIV Negative Negative Not done asymptomatic and dark brown skin lesions on lower limbs, 5∼15 mm sized nontender movable firm subcutaneous nodules 6 M/40 yr 1∼2 cm nontender, dull, red Asymptomatic Strongly positive Not done Not done subcutaneous nodules on chins pulmonary TB, (＞20 mm) heavy drinker 7, our case F/34 yr Subcutaneous skin colored or Latent TB Not done Negative Positive slightly erythematous round to oval nodules on leg TB: tuberculosis, PCR: polymerase chain reaction, F: female, M: male, HIV: human immunodeficiency virus.
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