CASE REPORT Indonesia Journal of Biomedical Science (IJBS) 2020, Volume 14, Number 1: 4-8 P-ISSN.2085-4773, E-ISSN.2302-2906 Papulonecrotic tuberculid: a case report

Ni Luh Putu Ratih Vibriyanti Karna1, Luh Made Mas Rusyati1*

ABSTRACT Introduction: Papulonecrotic tuberculid (PNT) is a chronic, ulcer, and scars, symmetrically on her arms, legs and trunk. recurrent, and symmetric eruption of necrotising skin papules in Mantoux skin test was strongly positive with 13 mm induration. crops involving the arms and legs, and healing with scar formation. Lymphohystiocytic vasculitis was found on cell pathology PNT is an uncommon disorder, occurring in less than 5 % of cases examination, there is no evidence of microbial growth in culture, of active TB. The pathophysiology of this disease has remained Ziehl-Neelsen staining and PCR was negative. She was given anti- controversial. with a rapid improvement after therapy for 6 months Case: A 31 years old Balinese woman, visited Outpatient Clinic with no significant adverse event. Department of Dermatology and Venereology Sanglah Hospital Conclusion: Treatment for six months using anti-tuberculosis Denpasar in 8th September 2003, she has complained of recurrent drugs provides satisfactory results with clinical improvement in ulcer for 14 years ago. The clinical feature showed papules, multiple patients with PNT.

Keywords: tuberculid, skin, disorder, infection, chronic. Cite this Article: Karna, N.L.P.R.V., Rusyati, L.M.M. 2020. Papulonecrotic tuberculid: a case report. IJBS 14(1): 4-8. DOI:10.15562/ijbs. v14i1.215

1Departement of Dermatology and INTRODUCTION there were 91 reported cases over 17 years, plus 12 Venereology, Faculty of Medicine, cases reported in 1986 from the United Kingdom Universitas Udayana-Sanglah Papulonecrotic Tuberculid (PNT) is asymmetrical General Hospital, Denpasar, Bali- for over 30 years. The decrease in the incidence of skin eruption characterised by groups of necrotic the disorder occurred in the mid-1900s since the Indonesia papules, chronic progressive, and disappear 1,2 effective control and treatment of TB sufferers up to by leaving scar tissue. Generally it affects the now.2 Rarely do PNT cases now cause these cases to extensors of the extremities, especially the knees, become dormant.3 elbows and dorsal parts of arms, also could extend 1,2 to the lower body. Until now the pathophysiology CASE REPORT of PNT is still controversial, some authors consider that this eruption is a hypersensitivity reaction to A 31-year-old woman, Balinese, unmarried, tuberculosis antigens resulting from the focus of working as a household assistant, came to the infection elsewhere, whereas other authors believe Dermatology and Venereology Outpatient Clinic that this eruption is the result of a hematogenous of the Sanglah General Hospital in Denpasar with infection spread to the skin.2 The typical condition complaints since two weeks there were patches and of this disease is that it can last a long time, wounds on her back, hands, feet, sometimes itchy often recur and last for years, even though some especially when sweating. This complaint has been spontaneous experience resolution. Several types felt for a long time, since the patient was 13 years of tuberculids have been reported, but PNT and old but often disappeared after seeing a doctor, and lichen scrofulosorum are actual tuberculids, while *Corresponding to: even disappeared without treatment. This disorder Luh Made Mas Rusyati; other forms may not have a specific relationship to starts from the right and left elbows, right and left 1,2 Departement of Dermatology and TB infection. Generally with young women and arms then the lower limbs right and left. In recent Venereology, Faculty of Medicine, children, two-thirds of cases under the age of 30 years the disease has been felt more severely and Universitas Udayana-Sanglah year.2 has spread to the body, which previously had General Hospital, Denpasar, Bali- Reports on PNT in the past literature on genital been more frequent in the arms and legs. Another Indonesia dermatology and pediatric health sciences are [email protected] illness that has suffered is a wound on the skin of often found, but currently PNT cases are very the neck, which left a scar. Patients themselves do Received: 2019-11-25 rare, even in populations with a high prevalence of not remember the treatment given when suffering Accepted: 2020-01-28 tuberculosis (TB). Worldwide PNT cases are less from the disease. At present the patient does not Published: 2020-01-29 than 5% of active TB cases. In South Africa in 1974, complain of coughing, and there is no history of the

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same disease in the family, only the mother of the scar tissue (Figure 1). Right and left elbows appear patient has ever coughed up blood that has received reddish papules and scar tissue (Figure 2). On the treatment at the primary health centre. right neck there was a scrofulodermal scarring During clinical examination blood pressure was (Figure 3). 110/70 mmHg, pulse 88 times per minute, and axilla Pada pemeriksaan thorax foto didapatkan temperature 37ºC. The general condition is rather fibroindurasi parahiler kiri.Pada pemeriksaan weak with pale skin without any regional lymph darah lengkap didapatkan peningkatan laju endap node enlargement. Dermatological status found on darah yaitu pada jam pertama 10 mm dan jam both legs appear to be swollen, dorsum parts appear kedua 50 mm, haemoglobin rendah yaitu 8,15 g/dl, hyperpigmented covered with several ulcers with a kesan anemia hipokromik mikrositer. Sedangkan diameter of 1 to 2 cm in pale color, some are covered pemeriksaan Mantoux test didapatkan positf with black coloured crusts. In other places, lesions dengan indurasi 13 mm. Pada pemeriksaan preparat appear to heal and leave scars (scar tissue). On the gram tidak dijumpai stafilokokus dan streptokokus. back there are reddish papules, pustules, and many On chest x-ray examination, fibroinduration was found in the left para hilar region. On complete blood examination, there was an increase in the rate of blood sedimentation of at the first hour is 10 mm and the second hour is 50 mm, mild anaemia (8.15 g/dl) with hypochromic microcytic red blood cell pattern. While the Mantoux test was positive with induration of 13 mm. On gram preparations there were no staphylococci and . On histopathological examination skin biopsy specimens were obtained the appearance of the skin consists of epidermis, dermis, adnexa, blood vessels and infiltrate perivascular inflammation. In this section, small blood vessels appear with Skin lession on back region Figure 1. mononuclear (lymphohistiocytic) infiltrate and polymorphonuclear, mild neutrophils, surrounding nucleic debris. No visible intraluminal fibrin pattern was seen. Whereas in the microbiological culture examination there was no germ growth. In Ziehl- Nielsen’s painting there was no M. tuberculosis found, and no particle of M. tuberculosis was found on the PCR examination (Figure 4). The patient is then diagnosed as a papulonecrotic tuberculid. Patients are consulted to the Lung Sub Division, Internal Medicine Department and get Rifampicin 450 mg/day, Ethambutol 750 mg/day, Isoniazid 300 mg/day (given for 2 months), then Figure 2. Skin lession on right elbow and right leg followed by Isoniazid 600 mg and Rifampicin 450 mg every 2 days for 4 months. The total is given for 6 months. Treatment with anti-TB drugs for 6 months gave a very good response, there were very significant clinical changes Figures( 5 and 6).

DISCUSSION Tuberculids are a group of skin eruptions associated with tuberculosis. Several types have been reported, but today many are considered to have no specific relationship to TB infection, only PNT and lichen scrofulosorum is considered by most authors to be the true tuberculid.1,2 In 1896 Darier was the first to explain this tuberculid and in 1936, Pautrier proved that PNT was a disorder associated with TB.2 Figure 3. Scrolufuderma scar on neck region Papulonecrotic tuberculid is symmetrical

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skin eruption, chronic and residive. Previously The typical clinical feature of PNT is small this disorder was often found, but now the case reddish papules that can be ulcerated in the middle, is very rare even in populations with a high TB within a few weeks they can disappear spontaneously prevalence.1,2 Children and young adults are more and leave scars (varioliform scar). Lesions appear susceptible to this disorder and women appear in a symmetrical form with predilection areas of to be at a slightly higher risk of this disorder.4,5 this disorder are the extensors of the extremities, Observations made in South Africa in 1974 found especially in the knees, elbows, and dorsal area two-thirds of cases under the age of 30 years.2 of the arms and lower limbs and can extend to other parts of the body such as the lower body and gluteal area. The emergence of new lesions among lesions that have experienced healing causes the lesions appear polymorphic. The colour of the red lesions to black, often covered with attached crust. In one study 30% of cases were obtained enlarged neck lymph nodes and some patients found to had .1,2 Nearly all patients showed a positive Mantoux test that was strongly positive, and this showed an active infection or had had a TB infection. A Mantoux skin test is a delayed-type hypersensitivity reaction (DTH). This DTH reaction is used as an indicator that a person has already been or is being exposed to an antigen, such as an example of a DTH reaction to a , an antigen which is a purified protein derivative (PPD). This reaction is an indication of the response of T cells to mycobacterium. Therefore, this eruption is believed to be a form of hypersensitivity reaction to tuberculosis (TB) antigen produced from focal Figure 4. Pathology Anatomy Examination and Polymerase Chain Reaction infection elsewhere, so other tests are needed to (PCR) find active TB or other forms of mycobacterial infection, including looking for possible infections in the genetical tract. women, which can increase the incidence of this disease in women. Even menstrual fluid culture and endometrial biopsy may be needed to reveal this disease.1 Erythrocyte sedimentation rate (ESR) often shows high numbers and can be used to monitor treatment. Which will decrease within 4-6 weeks after treatment begins.2 Chest x-ray is required to look for active TB or previous history of lung TB. Abdominal radiographs can show calcification in lymph node-specific for TB.2 The pathophysiology of PNT is still being debated.1,2 Most authors believe PNT is an Arthus reaction in which TB antigens or intact bacilli are initially emitted, and then followed by hypersensitivity reactions to these micro bacterial products presented in the skin. The removal of this product by mycobacterium organisms or antigens through a specific process is the process of opsonisation by antibodies that produce a complex immune formation, which will accumulate in the small blood vessels of the skin. This complex immunity will activate complement to induce leukocytoclastic vasculitis which further damages Figure 5. Skin lession after 3 months of treatment

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ulcers. Whereas examinations such as menstrual fluid culture and endometrial biopsy, abdominal radiographs were not done because the results of the other labs have supported the diagnosis of PNT. Histopathological features of PNT vary greatly depending on time to collect specimens, in the initial lesion, will show a vasculitis that is characterised by a specific pattern of the presence of leukocytoclastic with fibrinoid necrosis of blood vessel walls and karyomhectic debris. The main pattern is sometimes granulomatous vasculitis that causes thrombosis and total obstruction of the vascular ducts.1 However, some authors report the presence of lymphocytic vasculitis in the initial lesion and not leukoclastic vasculitis. Spongy images of perivascular oedema are reported as characteristic signs of this abnormality, followed by wedge-shaped necrosis, surrounded by infiltrating inflammation of the granulomatous with Langerhans giant cells and epithelioid histiocytes.1,2,8 Bacterial content in skin lesions is less than lesions in lungs, but the treatment used is the 2 Figure 6. Skin lession after 6 months of treatment same. The World Health Organization (WHO) recommends a combination of therapy with 4 drugs such as Isoniazid, Rifampicin, Pyrazinamide, Ethambutol to prevent PNT resistance, for a the vessel wall and the release of proteolytic enzymes minimum of 6 months.2,9,10 In this case there is a will cause focal tissue necrosis.2 very good and fast response that is in 4 weeks there Other authors oppose this pathophysiology, is a decrease in ESR to 1mm/hour in the first hour they assume that tuberculosis is a representation and 20 mm/hour at the second hour. Papulopustular of lesions on the skin due to hematogenous lesions experience involution by leaving scar tissue spread of bacilli to the skin and because the strong and new lesions do not appear after several months immunity in these individuals against tuberculosis of treatment, whereas the healing process of lesions causes germs to be destroyed rapidly and in some in the form of ulcers seems slower. cases autoinvolution of the lesions.2 Besides that, Patients with tuberculosis papulonecrotic can histologically, a leukoclastic vasculitis was not experience these abnormalities with years and found, they argued that the primary lesion showed cumulative, although there are reported to have a subacute of lymphohistiocytic vasculitis that spontaneous resolution. Give a fast and good caused vascular thrombosis and tissue necrosis. response to anti-TB treatment, rarely recurrence However, overall culture of the lesion was negative, after treatment, but complications in the form of with PCR examination by biopsy it was found that scar tissue that is difficult to avoid and some cases mycobacterial DNA chain was more than 50%.1,2,6,7 can become progressive .1,2 Polymerase chain reaction (PCR) is now widely used to detect the presence of mycobacterial DNA in skin specimens from patients with cutaneous CONCLUSION tuberculosis. In several studies, examinations There have been reported cases of PNT in women carried out on tuberculosis papulonecrotic aged 31 years, who suffered since 18 years. The lesions found Mycobacterium tuberculosis DNA diagnosis is made based on clinical, laboratory approximately 50%, this refutes the opinion of examination, histopathology, Mantoux tests, and PNT is a result of mycobacterial antigens but is a PCR examination. Treatment with anti-TB for 6 local infection.1,2,6,7 While research conducted in months gives a very good response. Singapore suddenly Mycobacterial DNA particles were found in all forms of tuberculosis variation.5 CONFLICT OF INTEREST In this patient PCR examination was done and no germ particles were found, where the examination The author declares there is no conflict of interest material was taken from skin lesions in the form of regarding publication of current report.

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ETHICAL CONSIDERATION Dermatopathol. 1996;18(2):172-185. 6. Quiros E, Bettinardi A, Piedrola G, Maroto MC. Detecton Patient had received signed inform consent of mycobacterial DNA in papulonecrotic tuberculid regarding publication of their respective photograph lesions by polymerase chain reaction. J Clin Lab Anal. 2000;14(4):133-135. in journal article. 7. Tan SH, Tan BH, Goh CL, Tan KC, Tan MF, Ng WC, Tan WC. Detection of Mycobacterium tuberculosis DNA using REFERENCES polymerase chain reaction in cutaneus tuberculosis and tuberculids. Int J Dermatol. 1999;38(2):122-127. 1. Rappeiner G, Wolff K. Tuberculosis and other Mycobacterial 8. Jordaan HF, Van Niekerk DJ, Louw M. Papulonecrotic infections In: Freedberg IM, Eisen AZ, Wolff K, et al. Eds. tuberculid. Aclinical, histopathological, and th Fitzpatrick’s Dermatology in General medicine. 6 edition. immunohistochemical study of 15 patients. Am J New York: McGraw-Hill; 2005; p. 1933-1971. Dermatopathol. 1994;16(5):474-485. 2. Tirumalae R, Yeliur I, Anthony M, Georhe G, Kenneth 9. Kullavanijaya P, Sirimachan S, Suwantaroj S. Papulonecrotic J. Papulonecrotic tuberculid-clinicopathologic and tuberculid: Necessity of long-term triple regimens. Int J molecular features of 12 Indian patients. Dermatol Pract Dermatol. 1991;30(7):487-490. Concept. 2014;4(2):17-22. 10. Barbagallo J, Tager P, Ingleton R, Hirch RJ, Weinberg JM. 3. Wilson-Jones E, Winkelmann RK. Papulonecrotic Cutaneous tuberculosis: Diagnosis and treatment. Am J tuberculid: Aneglected disease in Western countries. J Am Clin Dermatol. 2002;3(5):319-328. Acad Dermatol. 1986;14(5):815-826. 4. Freiman A, Ting P, Miller M, Greenway C. Papulonecrotic tuberculid: A rare form of cutaneous tuberculosis. Cutis. 2005;75(6):341-346. 5. Jordaan HF, Schneider JW, Schaaf HS, Victor TS, Geiger DH, Van Helden PD, Rossouw DJ. Papulonecrotic tuberculid in children. A case report of eight patients. Am J

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