Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2023;13(3):e2023154 1 Cyclophosphamide in a Recalcitrant Case of Nekam’s Disease Aishwarya Muddebihal1, Ananta Khurana1, Kabir Sardana1 1 Department of Dermatology Venereology and Leprosy, Atal Bihari Vajpayee Institute of Medical Sciences and Dr Ram Manohar Lohia Hospital, New Delhi, India Key words: Nekam’s disease, recalcitrant, cyclophosphamide Citation: Muddebihal A, Khurana A, Sardana K. Cyclophosphamide in a recalcitrant case of Nekam’s disease. Dermatol Pract Concept. 2023;13(3):e2023154. DOI: https://doi.org/10.5826/dpc.1303a154 Accepted: January 2, 2023; Published: July 2023 Copyright: ©2023 Muddebihal et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Dr. Ananta Khurana, Professor, Department of Dermatology, Venereology and Leprosy, Atal Bihari Vajpayee Institute of Medical Sciences and Dr Ram Manohar Lohia Hospital, New Delhi, -110001. Phone no: +91-9212370467 E-mail: drananta2014@gmail.com Ethics Statement: The patient in this manuscript has given written informed consent for publication of case details and clinical photographs. Introduction Keratosis Lichenoides Chronica, also called as Nekam’s dis- ease, is a rare acquired muco-cutaneous inflammatory dis- order affecting adults and rarely children. It is characterized clinically by asymptomatic violaceous papules and plaques arranged in linear and reticular fashion and histologically by interface dermatitis [1]. It may be associated with features like rosacea, seborrheic dermatitis like rash (75%), recur- rent oral aphthous ulcer (50%), palmoplantar keratoderma (40%) and nail dystrophy (30%) [2]. We report a rare con- dition in its classical form and a sustained remission with cyclophosphamide. Case Presentation A 25-year-old female, presented with 5-years history of mild itchy lesions which had started during pregnancy, and had gradually progressed. She also complained of burning sen- sation on eating. Cutaneous examination revealed multiple, linear, hyperkeratotic violaceous plaques over flexor aspect of upper limbs, dorsum of hands, trunk, abdomen, buttocks, and lower limbs. (Figure 1A) She also had rosacea-like le- sions on the face (Figure 1B) and multiple aphthous ulcers over bilateral buccal mucosa (Figure 1C), the combination of features suggesting Nekam’s disease. Histopathology revealed parakeratotic hyperkeratosis covering acanthotic and focally flattened epidermis and band-like lymphocytic infiltrate admixed with plasma cells abutting the basal layer which showed vacuolization con- firming the clinical diagnosis. Her routine blood investigations were normal. The patient had received methotrexate (7.5-15 mg for 3 months) and acitretin (25 mg once daily for 1 month) previously with no clinical improvement. She was subsequently administered pulse intravenous methylprednisolone 500 mg for 3  days 2 Research Letter | Dermatol Pract Concept. 2023;13(3):e2023154 which was deferred later due to ECG changes. She was then treated with cyclophosphamide 100mg once daily (OD) which was tapered to 50 mg OD after a month, followed by subsequent tapering to 50 mg alternate days. Progressive improvement occurred during this with resolution of muco- sal lesions and all cutaneous lesions with post inflammatory hyperpigmentation (Figure 1D) at the end of five months, at which point cyclophosphamide was stopped. The patient’s blood counts and urine analysis were closely monitored throughout the course of treatment and demonstrated no abnormalities. Four months later she had a mild recurrence which responded to cyclophosphamide 50mg given 3 days a week for a month. The patient has since been off systemic treatment with occasional minor localized recurrences man- ageable with topical agents alone. Conclusions Nekam’s disease and other lichenoid disorders are charac- terized by an interface inflammatory cell infiltrate largely consisting of lymphocytes and plasma cells. At a molecular level CD4+ Th1 cells and CD8+ T lymphocytes, and Natural killer cells mediate the damage to basal cells in this group of disorders [3]. Phototherapy, retinoids, methotrexate, dap- sone, steroids, antimalarials, ciclosporin, efalizumab, have all been tried with variable efficacy in Nekam’s disease [4]. Cyclophosphamide is a potent immunosuppressive agent which has demonstrated efficacy in treating resistant der- matoses including recalcitrant lichen planus and cutaneous lupus, dermatomyositis, PLEVA, refractory graft versus host disease, etc; all characterized by an interface infiltrate rich in Figure 1. (A) Erythematous to violaceous papules and plaques in reticular fashion over both upper limbs. (B) Rosacea like lesions on face. (C) Aphthous ulcer over right buccal mucosa. (D) Resolution of cutaneous lesions with post inflammatory hyperpigmentation after five months of cyclophosphamide. Research Letter | Dermatol Pract Concept. 2023;13(3):e2023154 3 lymphocytes. This is as lymphocytes are exquisitely sensitive to the drug owing to lack of detoxifying enzyme aldehyde dehydrogenase [5,6]. The reported case thus exemplifies the drug use in yet another typically difficult to treat dermato- logic condition, and adds to the armamentarium to deal with this recalcitrant disorder. References 1. Aruna C, Ramamurthy DV, Neelima T, Bandaru H. Nekam’s disease. Indian Dermatol Online J. 2016;7(6):520-522. DOI: 10.4103/2229-5178.193923. PMID: 27990390. PMCID: PMC5134169. 2. Taberner R, Puig L, Fernández-Figueras T, Alomar A. Ker- atosis lichenoides chronica.  J Eur Acad Dermatol Venereol. 2001;15(1):84-85. DOI: 10.1046/j.1468-3083.2001.00178-7.x. PMID: 11451338. 3. Tziotzios C, Lee JYW, Brier T, et al. Lichen planus and li- chenoid dermatoses: Clinical overview and molecular basis. J Am Acad Dermatol. 2018;79(5):789-804. DOI: 10.1016/j.jaad .2018.02.010. PMID: 30318136. 4. Nomura T, Toichi E, Miyachi Y, Kabashima K. A Mild Case of Adult-Onset Keratosis Lichenoides Chronica Successfully Treated with Narrow-Band UVB Monotherapy. Case Rep Der- matol. 2012;4(3):238-241. DOI: 10.1159/000345277. PMID: 23185159. PMCID: PMC3506084. 5. Deakin CT, Campanilho-Marques R, Simou S, et al. Efficacy and Safety of Cyclophosphamide Treatment in Severe Juvenile Der- matomyositis Shown by Marginal Structural Modeling. Arthritis Rheumatol. 2018;70(5):785-793. DOI: 10.1002/art.40418. PMID: 29342499. PMCID: PMC5947636. 6. Mayer J, Krejcí M, Doubek M, et al. Pulse cyclophosphamide for corticosteroid-refractory graft-versus-host disease. Bone Marrow Transplant. 2005;35(7):699-705. DOI: 10.1038/sj.bmt.1704829. PMID: 15696180.