Dermatology: Practical and Conceptual Observation | Dermatol Pract Concept 2016;6(4):4 19 DERMATOLOGY PRACTICAL & CONCEPTUAL www.derm101.com Introduction Pityriasis rubra pilaris (PRP) is a chronic disorder of kera- tinization of unclear pathogenesis [1]. It typically manifests as erythematous and scaly cutaneous plaques with islands of spared skin associated with follicular scaly papules and orange palmar and plantar keratoderma. Although PRP is usually idiopathic, certain trigger events have occasionally been reported, mainly traumatic, infectious (infections of streptococcus, cytomegalovirus and rubella) or after vaccination [2]. However, PRP-like eruptions induced by drugs have been described, albeit rarely [3-5]. We report a case of PRP-like eruption that occurred dur- ing the initiation of insulin therapy. To our knowledge, no previous similar cases have been reported. Case report A 29-year-old man was referred to our department because of a generalized erythematosquamous and non-pruritic der- Pityriasis rubra pilaris-like eruption following insulin therapy initiation Talel Badri1, Anissa Zaouak1, Ghozlane Lakhoua2, Wafaa Koubaa3, Sami Fennich1, Ahmed Zaiem2 1 Department of Dermatology, Habib Thameur Hospital, Faculty of Medicine, University of Tunis El Manar, Tunisia 2 National Center of Pharmacovigilance, Faculty of Medicine, University of Tunis El Manar, Tunisia 3 Laboratory of Pathology, Habib Thameur Hospital, Faculty of Medicine, University of Tunis El Manar, Tunisia Key words: pityriasis rubra pilaris, insulin, drug-induced, cutaneous rash, skin Citation: Badri T, Zaouak A, Lakhoua G, Koubaa W, Fennich S, Zaiem A. Pityriasis rubra pilaris-like eruption following insulin therapy initiation. Dermatol Pract Concept 2016;6(4):4. doi: 10.5826/dpc.0604a04 Received: May 31, 2016; Accepted: July 30, 2016; Published: October 31, 2016 Copyright: ©2016 Badri et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: None. Competing interests: The authors have no conflicts of interest to disclose. All authors have contributed significantly to this publication. Corresponding author: Talel Badri, MD, Department of Dermatology, Habib Thameur Hospital, 8 rue Ali Ben Ayed, 1008 Tunis, Tunisia. Tel. +216.98.829.300. Email: talel_badri@yahoo.fr Pityriasis rubra pilaris (PRP) is a chronic disorder of keratinization of unclear pathogenesis. PRP-like eruptions induced by drugs have rarely been described. A previously healthy 29-year-old man pre- sented with a generalized, rapidly spreading, erythematosquamous dermatosis, that started three days after initiation of subcutaneous insulin therapy for diabetes mellitus type 1. Clinical and histopatho- logical features were consistent with a PRP-like eruption, possibly due to insulin therapy. The patient was switched to insulin analogue therapy and a complete healing of all lesions was achieved after two months. No recurrence was seen after one year of follow-up. Other possible etiologies of PRP were excluded. The mechanism leading to the occurrence of drug-in- duced PRP-like eruptions are not clear. Since PRP may occur in the context of immunological anoma- lies, it is possible that diabetes mellitus type 1 may have been a predisposing condition for the develop- ment of PRP in this case. ABSTRACT mailto:talel_badri@yahoo.fr 20 Observation | Dermatol Pract Concept 2016;6(4):4 Histopathology A skin biopsy was performed, and histopathological exami- nation revealed irregular hyperkeratosis with orthokeratosis and parakeratosis in addition to dilated hair follicles and keratinous plugs (Figure 3). Diagnosis and outcome A diagnosis of a PRP-like eruption, possibly induced by insulin therapy, was suspected. Insulatard® and Actrapid® were discontinued and the patient was switched to insulin analogue therapy: glargine (Lantus®) and glulisine (Apidra®). Skin lesions were treated with betamethasone ointment (30 g daily) and petrolatum. A progressive resolution of the rash was obtained and complete healing of all cutaneous lesions was achieved after two months. Skin tests (patch test and intradermal test) with insulin and its additives were con- sidered but the patient refused them. No recurrence of skin lesions was seen after one year of follow-up. Discussion The acute onset of the dermatosis after insulin therapy initiation, the rapid favorable outcome after human insulin withdrawal, as well as the absence of recurrence after one year of follow-up, were suggestive of a possible responsibil- ity of insulin therapy for the genesis of the PRP-like eruption in our patient. Although possible, a fortuitous association “insulin therapy—idiopathic PRP” seems unlikely in our case because of the rapid resolution of the rash, as opposed to the classical chronic course of idiopathic PRP, even with the use of systemic treatments, such as retinoids [1]. Drug-induced PRP-like eruptions are rare, and the mecha- nisms leading to their occurrence have not been clearly elu- matosis that had rapidly spread during the previous week. It had started three days after initiation of Insulatard® ([Neu- tral Protamine Hagedorn insulin]: 12 IU in the morning; 8 IU in the evening) and Actrapid® ([soluble regular insulin]: 4 IU b.i.d.) for a recently diagnosed diabetes mellitus type 1. The patient’s past medical history showed neither personal nor familial previous episodes of papulosquamous disorders. No other medical condition or concomitant medication intake were noticed. The patient had not received any vac- cination during the previous five years and he denied any trauma. Cutaneous examination revealed large areas of erythema- tous orange scaly plaques with small islands of uninvolved skin, as well as follicular keratotic papules. These lesions were located on the trunk (Figure 1) and limbs. The patient also had an orange-red waxy keratoderma on his palms and soles with some fissures (Figure. 2). No nail changes and no mucous membrane involvement were observed. There was no other organ or systemic involvement. Figure 1. Erythematous scaly papules coalescent into large plaques on the trunk. [Copyright: ©2016 Badri et al.] Figure 2. Bilateral orange-red waxy keratoderma. [Copyright: ©2016 Badri et al.] Figure 3. Irregular hyperkeratosis with alternating orthokeratosis and parakeratosis and corneal plugs characteristic of pityriasis rubra pilaris (hematoxylin-eosin X100). [Copyright: ©2016 Badri et al.] Observation | Dermatol Pract Concept 2016;6(4):4 21 References 1. Gemmeke A, Schönlebe J, Koch A, Wollina U. Pityriasis rubra pilaris—a retrospective single center analysis over eight years. J Dtsch Dermatol Ges 2010;8(6):439-44. PMID: 15982236. 2. Naciri Bennani B, Cheikh Rouhou H, Waton J, et al. Pityri- asis rubra pilaire après vaccination. Ann Dermatol Vene- reol 2011;138(11):753-6. PMID: 22078037. DOI: 10.1016/j. annder.2011.01.049. 3. Paz C, Querfeld C, Sbea CR. Sorafenib-induced eruption resem- bling pityriasis rubra pilaris. J Am Acad Dermatol 2011;65(2):452- 3. PMID: 21763585. DOI: 10.1016/j.jaad.2010.03.015. 4. Plana A, Carrascosa JM, Villavella M, Ferrandiz C. Pityriasis ru- bra pilaris-like reaction induced by imatinib. Clin Exp Dermatol 2013;38(5):520-2. PMID: 23777493. DOI: 10.1111/ced.12081. 5. Schmutz JL, Trechot P. Telaprevir-induced pityriasis rubra pilaris- like drug eruption. Arch Dermatol 2012; 148(10):1215-7. PMID: 23069976. DOI: 10.1001/archdermatol.2012.2039. 6. Feinglos MN, Jegasothy BV. “Insulin” allergy due to zinc. Lancet 1979;1(8108):122-4. PMID: 84149. 7. Raap U, Liekenbrocker T, Kapp A, Wedi B. Delayed-type hypersen- sitivity to protamine as a complication of insulin therapy. Contact Dermatitis 2005;53(1):57-8. PMID: 15982236. cidated [2-5]. The pathogenesis in our patient is also unclear. Although insulin therapy is largely used worldwide, its asso- ciation with PRP-like eruptions has never been reported. However, since PRP may occur in certain cases with underly- ing immunological anomalies [2], it is possible that diabetes mellitus type 1 might have contributed to the development of the dermatosis in our patient, after insulin therapy initiation. Insulin preparations containing zinc or protamine (such as Insulatard®) may also cause a delayed-type hypersensitivity [6,7]. However, in the absence of skin tests, the role of such additives in the genesis of the dermatosis in our patient could not be determined. Conclusion Although a fortuitous association could not totally be ruled out, a cutaneous reaction induced by insulin therapy in a context of underlying immunological anomalies might be the cause of the dermatosis in our patient.