Autoimmune Progesterone Dermatitis: a Complex 6

Practitioner's Corner 348

Low-dose rituximab as an adjuvant therapy in pemphigus. Indian J Dermatol Venereol Leprol. 2017;83:317-25. Autoimmune Progesterone Dermatitis: A Complex 6. Hertl M, Jedlickova H, Karpati S, Marinovic B, Uzun S, Yayli S, Case et al. Pemphigus. S2 Guideline for diagnosis and treatment - guided by the European Dermatology Forum (EDF) in Montoro J1,2, Miquel FJ1,3, Quecedo E3, Martínez M2, Orduña A2, cooperation with the European Academy of Dermatology Gimeno E3, Valverde A4 and Venereology (EADV). J Eur Acad Dermatol Venereol. 1Cutaneous Allergy Unit, Hospital Arnau de Vilanova, Valencia, 2014;29:405-14. Spain 7. Sanchez J, Ingen-Housz-Oro S, Chosidow O, Antonicelli F, 2Allergy Service, Hospital Arnau de Vilanova, Valencia, Spain Bernard P. Rituximab as Single Long-term Maintenance 3Dermatology Service, Hospital Arnau de Vilanova, Valencia, Therapy in Patients With Difficult-to-Treat Pemphigus. JAMA Spain Dermatology. 2018;154:363-5. 4Department of Human Anatomy and Embryology, Faculty of 8. Wang H, Liu C, Li Y, Huang Y. Efficacy of Rituximab for Medicine and Odontology, University of Valencia, Valencia, Spain Pemphigus: A Systematic Review and Meta-analysis of Different Regimens. Acta Dermatol Venereol. 2015;95:928- J Investig Allergol Clin Immunol 2018; Vol. 28(5): 348-350 32. doi: 10.18176/jiaci.0284 9. Kanwar A, Vinay K, Sawatkar G, Dogra S, Minz R, Shear N, et al. Clinical and immunological outcomes of high- and Key words: Autoimmune progesterone dermatitis. GnRH analogues. low-dose rituximab treatments in patients with pemphigus: Atopic dermatitis. Food allergy. Lipid transfer protein (LTP). a randomized, comparative, observer-blinded study. Br J Palabras clave: Dermatitis autoinmune por progesterona. Análogos de Dermatol. 2014;170:1341-9. la GnRH. Dermatitis atópica. Alergia alimentaria. Proteína transportadora 10. Schoergenhofer C, Schwameis M, Firbas C, Bartko J, de lípidos (LTP). Derhaschnig U, Mader RM, et al. Single, very low rituximab doses in healthy volunteers – a pilot and a randomized trial: implications for dosing and biosimilarity testing. Scient Rep. 2018;8:124-5. Autoimmune progesterone dermatitis (APD) is an uncommon condition and often a diagnostic challenge. It is characterized by hypersensitivity to progestogens that manifests clinically in a cyclical manner beginning some days before onset of menstruation and resolving during or shortly Manuscript received March1, 2018; accepted for publication after the menstrual period. June 12, 2018. Clinical presentation is extremely variable, the most common forms being urticaria and eczematous dermatitis. Mauro Alaibac Unit of Dermatology Other manifestations include morbilliform exanthema, bullous University of Padua eruptions, erythema multiforme, and even purpura [1,2]. Via Gallucci 4 The first symptoms can arise as early as menarche, although 35128 Padova, Italy onset during pregnancy or after hormonal therapy is common. E-mail: [email protected] No specific histopathologic features have been described. Diagnosis is based on the clinical history and confirmed by a positive intradermal test with progesterone. Therapy usually involves suppression of ovulation using different strategies, including contraceptive pills, GnRH analogues, and danazol. Other options in refractory cases are desensitization [3] and, as a last resort, bilateral oophorectomy. We report the case of a 50-year-old woman who was diagnosed with atopic dermatitis 12 years ago. She had experienced clinical worsening during the last 2 years and received cyclosporine (200 mg daily) owing to the failure of previous treatments (topical and oral corticosteroids, bilastine, pimecrolimus, UV-B phototherapy, and off-label omalizumab). Skin biopsy revealed spongiotic dermatitis with no other findings. The patient was referred to our cutaneous allergy unit for patch testing, which yielded negative results with the Spanish baseline series. During history taking, the patient reported that she had been experiencing cyclical flares of her dermatitis over the last 6 months, involving mainly the face and neck (Figure, A). The flares started on days 8-12 of the menstrual cycle and resolved on days 1-2 of menstruation.

A B syndrome with recurrent dermatitis outbreaks that were initially related to the ingestion of apple and herb juice. Prick tests and specific IgE to environmental allergens and foods yielded positive results (Figure, C). Nuts, apple, and peach, which contain lipid transfer protein, were considered clinically relevant. No clinical correlations were observed for the other foods to which the patient was sensitized. Oral symptoms and flare-ups of dermatitis resolved when the culprit foods were avoided, and the lesions of atopic dermatitis were better controlled. The patient’s APD symptoms are now minimal, with well- tolerated, faint facial erythema once or twice monthly. Provided that APD was controlled, and taking into C Prick Test, mm Specific IgE, kU/L account possible long-term adverse effects, we reduced the dose of triptorelin to 1.87 mg and increased the dosing LTP (Pru p3) 5×5 3.38 interval to 6 weeks for 2 additional doses. The patient stopped Corn 5×5 2.36 triptorelin 8 months ago without worsening, even after 4 menstrual cycles, and with detectable serum progesterone Almond 3×3 ND levels. Current therapy for atopic dermatitis consists only of Hazelnut 3×3 0.03 emollients and occasional applications of methylprednisolone Peanut 3×3 0.05 aceponate cream. We report a complex and unusual case, in which different Strawberry 3×3 ND forms of allergic disease co-occur, namely, atopic dermatitis, Apple 3×3 0.21 APD, and food allergy. Peach 3×2 ND We infer that the patient had had atopic dermatitis for over 12 years, with significant worsening in the last 2 years, Artemisia 3×3 0.08 probably related to superimposed APD that could be suspected Dog dander 3×3 ND because she reported cyclical aggravation of her dermatitis during the previous few months. The patient has taken oral Cat dander 4×4 ND contraceptives containing progestagen for dysmenorrhea (between the ages of 18 to 23 years and for some months Figure. A, Involvement of the face and neck (arrows). B, Intradermal test with medroxyprogesterone 50 mg/mL. Positive result after 30 hours. at age 42). Once APD was controlled, the noncyclical C, Positive prick test and specific IgE. ND indicates not done; LTP, lipid manifestations of atopic dermatitis improved considerably, transfer protein. thus enabling withdrawal of cyclosporine and reducing the need for oral corticosteroids. The negative result of the first intradermal test with We suspected APD and performed prick and intradermal medroxyprogesterone, while the patient was still receiving tests with medroxyprogesterone up to 50 mg/mL in aqueous cyclosporine, along with the positive late reaction observed solution. The results were negative. This test was repeated 3 weeks after stopping the drug, supports the hypothesis that, 3 weeks after cyclosporine was discontinued, and a late in this case, the pathogenetic mechanism depends on a type IV, positive reaction (30 hours) to the prick and intradermal test T cell–mediated hypersensitivity reaction. This contrasts was obtained, with erythema and papules that took >48 hours with most previously published cases, in which immediate to resolve (Figure, B). reactions predominate. We found only 1 report describing a After gynecologic assessment, the patient was started on late reaction [4]. It is noteworthy that cyclosporine inhibited nasal nafarelin, a GnRH analogue (400 µg daily). The drug was the intradermal test, yet it was not able to control APD well tolerated, and the next flare was of much lower intensity. outbreaks. This observation could be explained by assuming In parallel, the cyclosporine dose was tapered by 50 mg that endogenous progesterone was probably a stronger every other week until complete withdrawal. immunologic stimulus than the concentration of intradermal Four months later, nasal nafarelin was replaced with progestagen. triptorelin (monthly 3.75-mg injections), since this was more Suppressing ovulation for 12 months undoubtedly comfortable for the patient, leaving the first option as rescue modified the course of APD, with the result that the patient medication. could tolerate endogenous progesterone, as she had normal Once the patient started therapy with nafarelin, the dose menstrual cycles after stopping triptorelin. of oral deflazacort was reduced to only 15-30 mg on 1-2 days Type I IgE-mediated hypersensitivity is an aggravating per month to manage occasional flare-ups of dermatitis, factor in atopic dermatitis. The clinical expertise of the which at that time were almost controlled with topical physician is crucial in determining the relevance of allergic methylprednisolone aceponate. sensitizations detected by prick testing or in vitro tests Four months later, atopic dermatitis and APD were and the potential role that allergen exposure might play in well controlled, although the patient developed oral allergy specific cases [5]. In the patient we report, sensitization to

the panallergen lipid transfer protein could have caused atopic dermatitis before the onset of symptoms of oral allergy Lichenoid Contact Dermatitis Induced by Semen syndrome, although with no clear clinical correlation. In any Sinapis Albae case, avoidance of clinically relevant culprit foods (all of which contain lipid transfer protein) eventually helped to optimize Guo S1,2, Jiang J-F2, Tan C2 control of atopic dermatitis, thus highlighting the importance of 1First Clinical College, Nanjing University of Chinese Medicine, a thorough allergology work-up in difficult-to-control disease, Nanjing, China in addition to merely prescribing symptomatic treatment. 2Department of Dermatology, Affiliated Hospital of Nanjng University of Chinese Medicine, Nanjing, China. Funding The authors declare that no funding was received for the J Investig Allergol Clin Immunol 2018; Vol. 28(5): 350-352 doi: 10.18176/jiaci.0286 present study. Key words: Contact Dermatitis. Lichenoid. Acupoint. Semen Sinapis Conflicts of Interest Albae. The authors declare that they have no conflicts of interest. Palabras clave: Dermatitis de contacto. Liquenoide. Acupuntos. Semillas de mostaza blanca. References

1. Grunnet KM, Powell KS, Miller IA, Davis LS. Autoimmune progesterone dermatitis manifesting as mucosal erythema The clinical manifestations of contact dermatitis are multiforme in the setting of HIV infection. JAAD Case Rep. varied and present as either eczematous or noneczematous 2017;3:22-4. eruptions [1]. Lichenoid contact dermatitis (LCD) is a rare 2. Özmen I, Aktürk E. Autoimmune progesterone dermatitis noneczematous form of contact dermatitis. It is caused by presenting with purpura. Cutis. 2016;98:E12-E13. multiple factors, including exposure to plants, drugs, and 3. Foer D, Buchheit KM, Gargiulo AP, Lynch DM, Castells M, chemicals [2]. Nonetheless, to the best of our knowledge, Wickner PG. Progestogen hypersensitivity in 24 cases: lichenoid contact dermatitis induced by an acupoint herbal diagnosis, management and proposed renaming and patch (AHP) with Semen Sinapis Albae (SSA) has never classification. J Allergy Clin Immunol Pract. 2016;4:723-9. been reported. 4. Frieder J, Younus M. Autoimmune progesterone dermatitis A 55-year-old Chinese man was evaluated for a 4-month with delayed intradermal skin reaction: A case report. Ann history of nummular eruptions on an area treated with AHP. He Allergy Asthma Immunol. 2016;117:438-9. had a 14-year history of chronic obstructive pulmonary disease 5. Silvestre JF, Romero D, Encabo B. Atopic dermatitis in adults: with repeated exacerbations in winter. Following a prescription a diagnostic challenge. J Investig Allergol Clin Immunol. from a herbalist, AHP with SSA seeds was applied twice, on 2017;27:78-88. June 12 and 22, 2017. Twenty-four hours after the second application, each patch was detached with no noticeable cutaneous abnormalities. One month later, pruritic erythema and pin-sized papules appeared at the site. The primary eruptions became progressively pigmented and coalesced and did not fade with discontinuation of SSA or recede with the Manuscript received April 9, 2018; accepted for publication June 14, 2018. administration of topical corticosteroids and antihistamines. The patient was otherwise in good health and denied exposure Javier Montoro Lacomba to SSA before treatment of AHP. Skin examination revealed Unidad de Alergia Cutánea multiple nummular lesions distributed bilaterally along the Servicio de Alergia, Hospital Arnau de Vilanova spine, each overlaying a specific Back-shu acupoint. The Calle San Clemente 12 lesions comprised demarcated erythematous macules and 46015 Valencia, Spain plaques. Some of the lesions were entirely pigmented or E-mail: [email protected] overlapped with pin-sized papules (Figure, A). A skin biopsy displayed parakeratosis, acanthosis, and focal spongiosis in the epidermis. An infiltration of band-like mononuclear cells was visible along the dermoepidermal junction. There was no evidence of liquefaction of the basal cell layer or hyaline bodies (Figure, B). The patient was diagnosed with lichenoid contact dermatitis induced by SSA. The lesions did not improve with 1 month of topical application of 0.1% tacrolimus and persisted during follow-up. The remedy of AHP was firstly introduced in the Chinese medical book Prescriptions for Fifty-two Diseases written in