581737

case-report2015

CMSXXX10.1177/1203475415581737Journal of Cutaneous Medicine & SurgeryGill and Pratt

Case Report

A Severe Case of Recalcitrant Pompholyx

Journal of Cutaneous Medicine and Surgery 2015, Vol. 19(5) 494­–497 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1203475415581737 jcms.sagepub.com

Jeewanjit Gill1 and Melanie Pratt2

Abstract Background: Pompholyx is an inflammatory vesiculobullous skin disease of the hands and feet belonging to the spectrum of eczema. Objective: To report a severe case of pompholyx, its clinical presentation, and its management. Methods: A medical chart review was conducted on a patient with this condition. Results: The patient was patch tested according to the North American Contact Dermatitis Group (NACDG) Standard Screening Series, and results were negative. In the past, she was treated with corticosteroid creams as well as narrow band ultraviolet B (UVB), and Psoralen ultraviolet A (PUVA) therapies, and none were beneficial. When the frequency of the episodes increased, methotrexate was introduced but failed to control the condition. Next, mycophenolate mofetil was started and gradually increased to 3.5 g daily along with a separate trial of radiotherapy with marked success. Conclusion: Pompholyx can be challenging to manage, and treatment can involve an assortment of therapies over a prolonged period of time. Résumé Contexte : Le pompholyx, ou dysidrose, est une maladie inflammatoire vésico-bulleuse des mains et des pieds qui appartient au spectre de l’eczéma. Objectif : Faire état d’un cas grave de pompholyx, de sa présentation clinique et de sa prise en charge. Méthodologie : Étude du dossier médical d’une patiente atteinte de cette maladie. Résultats : La patiente a été soumise à des tests épicutanés standards (série de dépistage du North American Contact Dermatitis Group (NACDG)) et les résultats ont été négatifs. Par le passé, elle avait reçu un traitement de crèmes corticoïdes, de lumière ultraviolette B (UVB) à bande étroite et une PUVA-thérapie (psoralène et lumière ultraviolette A), sans succès. Lorsque la fréquence des épisodes s’est accrue, le méthotrexate a été inclus dans le régime thérapeutique, mais sans réussir à maîtriser la maladie. La patiente a ensuite reçu du mycophénolate mofétil, dont la dose a graduellement été augmentée à 3,5 g par jour, en même temps qu’un traitement distinct de radiothérapie a été mis à l’essai, avec un succès marqué. Conclusion : Le pompholyx peut être difficile à gérer et le traitement peut nécessiter un éventail de thérapies pendant une période de temps prolongée. Keywords dermatitis, immunology

Introduction Pompholyx is an inflammatory vesiculobullous skin disease of the hands and feet belonging to the spectrum of eczema. True pompholyx is a rare episodic bullous condition that should be differentiated from dyshidrotic eczema. Dyshidrotic eczema is characterized by smaller vesicular lesions along the lateral borders of the fingers, palms, and soles in the absence of any large bullae. Dyshidrotic patterns can be seen in many types of eczema such as atopic dermatitis, systemic contact dermatitis, and allergic contact dermatitis. In our view, these dramatic, severe, explosive large bullae on the palms and ventral fingers and sometimes the plantar aspect of the feet that are episodic and can last about 7 to 10 days represent a distinct rare entity known as pompholyx.

This is a burning and very pruritic vesiculobullous eruption where secondary infection with Staphylococcus aureus can occasionally be seen. Pompholyx can be a difficult condition to treat due to the thick overlying horny layer, pronounced spongiosis and accumulation of edema fluid in regions with a thick epidermis, and the abundance of eccrine sweat glands.1,2 1

University of Ottawa, Ottawa, ON, Canada The Ottawa Hospital, Ottawa, ON, Canada

2

Corresponding Author: Jeewanjit Gill, University of Ottawa, 451 Smyth Road Ottawa, ON K1H8M5, Canada. Email: [email protected]

Gill and Pratt In the majority of patients this condition seems to be idiopathic, but it can be aggravated by environmental conditions or activities that promote sweating or can be due to contact allergy.3 Pompholyx tends to present in patients during summer months or in those who work in hot, humid conditions.3 This condition is more common in women and individuals under stress.4 When establishing a diagnosis of pompholyx, clinicians need to consider several important differential diagnoses by taking a focused history, conducting a thorough clinical evaluation, and ordering appropriate investigations such as patch testing, histopathology, and microbiologic and mycological laboratory tests.2 Once a diagnosis is established, treatment needs to be monitored and adjusted over time due to the chronic relapsing nature of the disease and its limited response to various treatments in some patients. The aim of this report is to demonstrate a severe case of recalcitrant pompholyx, its clinical presentation, and the management of this condition.

Case A 34-year-old female presents with a history of developing bullae on her lateral fingers that started during university when she was 19 years old. The patient has a medical history of hay fever and does not smoke. She is currently employed as an administrative government worker. Her medical history includes hypertension, degenerative disc disease, obesity, and one episode of a deep vein thrombosis (DVT) in December 2012. She is regularly followed by the thrombosis unit. Her current weight is 380 lb. Her medications include pregabalin (Lyrica) 75 mg twice a day since June 2012; celecoxib (Celebrex) 200 mg, 1 to 2 tablets per day since June 2012; olmesartan-medoxomil/hydrochlorothiazide (Olmetec) 40 mg/12.5 mg since September 2012; warfarin (12.5 mg on Monday and Friday of the week and 22.5 mg for the remaining days of the week) since January 2013; and risedronate (Actonel) 35 mg, 1 tablet per week since April 2013. She also received 2 injections of enoxaparin of 150 mg per week for 3 weeks in December 2012. Her skin condition began 15 years ago, which predated all drugs. Originally, she would have an episode every 6 months, which would last about a week, and this pattern continued for 8 years. From 2003 onward, she began having more episodes every summer lasting 7 to 10 days, and these gradually increased in frequency to every few weeks throughout the year. In the past, she was treated with an assortment of corticosteroid creams, tar preparations, and narrow band ultraviolet B (311 nm) (UVB) and Psoralen ultraviolet A (320-400 nm) (PUVA) therapies, of which none were beneficial. Oral prednisone was the only medication that seemed to alleviate the condition. She would require 7 to 14 days of prednisone starting at 40 mg, then weaned over the course.

495 Examination of the patient at presentation in 2010 to her present dermatologist revealed large taut bullae on the palms and on the lateral and ventral fingers. A diagnosis of pompholyx was made. Skin punch biopsy confirmed this diagnosis of a spongiotic, eczematous process. The patient was patch tested to the North American Contact Dermatitis Group (NACDG) Standard Screening Series of 70 allergens, Chemotechnique cosmetics and plant series (Chemotechnique Diagnostics, Malmo, Sweden), and Trolab perfume and flavour series (Omniderm Pharma Canada Inc). Patch testing was performed with a standardized technique with Finn Chambers (Epitest Ltd Oy, Tuusula, Finland) on Scanpore tape (Norgesplaster Alpharma A/S Vennesla, Norway). The patches remained in place for 48 hours; test sites were evaluated at 48 hours and again at 120 hours after initial placement according to the NACDG guidelines, and results were negative. The frequency of the episodes increased to every few weeks; therefore, methotrexate was introduced as a steroidsparing agent in addition to prednisone. The patient had a chest radiograph, human immunodeficiency virus (HIV) count, hepatitis screen, tubercle bacillus (TB) skin test, liver function tests (LFTs), complete blood count (CBC), creatinine level, and platelet count. Chest radiograph demonstrated no active plural parenchymal abnormalities, the cardiomediastinal silhouette was normal, and there were minimal degenerative changes of the thoracic spine. The HIV and hepatitis (hepatitis B surface antigen and hepatitis C) screens and TB skin test were negative. The LFTs, CBC, creatinine level, and platelet count were normal. Methotrexate was initiated at a starting dose of 10 mg once a week, which was increased to 15 mg after a few weeks. Folic acid was also started at a dose of 1 mg daily except on the day methotrexate was taken. Later, the methotrexate was further increased to 20 mg weekly as the prednisone dose was weaned down and eventually discontinued. The patient’s pompholyx consistently flared, so her prescription eventually changed to mycophenolate mofetil at a starting dose of 500 mg twice a day, which was gradually increased to 1.5 g twice a day. Mycophenolate mofetil was momentarily discontinued for 10 days to see whether it was truly helping and also to present the patient at a clinical meeting on hand dermatitis, to which the patient agreed. A severe flare seen in Figure 1 resulted. Mycophenolate mofetil was then restarted at 1.5 g twice a day and eventually increased to 3.5 g daily with a weaning dose of oral prednisone. Her control was partial, necessitating the need for consideration of a new prescription. The patient was subsequently tested for the thiopurine-Smethyl transferase (TPMT) gene. Since she proved to have the homozygous normal genotype, the next consideration for prescription was azathioprine (Imuran). Unfortunately, at the same time, the patient developed a DVT and was put on long-term warfarin, which has potential to interact with azathioprine, making it less desirable to use. Cyclosporine was

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Figure 1.  Pompholytic bullous eruptions presenting on the (a) palmar and (b) dorsal aspects of the left hand.

not a good option either because the patient has hypertension. The patient’s prescription was changed to azathioprine 50 mg 3 times a day along with a weaning dose of oral prednisone. A referral to radiation oncology was also made to explore the possibility of radiation therapy. Radiotherapy treatment consisted of 2 sessions per week for a total of 4 weeks with a dosage of 50 radians per session to one hand while leaving the other untreated hand as a control. A marked improvement was noted, and subsequent eruptions were milder and less frequent. Mycophenolate mofetil was continued at a dose of 500 mg 3 times a day, and radiotherapy will be reinitiated during a severe flare-up.

Discussion This case describes the clinical course of a patient with a severe recalcitrant form of pompholyx and demonstrates the need to try a variety of different treatments to successfully manage this condition. Pompholyx is diagnosed after taking a careful history and by conducting a thorough clinical evaluation and investigations to target the underlying cause of this condition. The differential diagnoses of pompholyx includes dyshidrosiform bullous pemphigoid, dyshidrotic tinea, linear IgA disease with pompholyx, epidermolysis bullosa, erythema multiforme, hand-foot-and-mouth disease, herpes infection, human T-lymphotropic virus-1 (HTLV-1) infection, fixed drug eruptions, friction blisters, pemphigus vulgaris, bullous impetigo, and psoriasis pustulosa.1,2 Pompholyx can also be associated with atopic dermatitis, contact dermatitis,2,5 pellagra after sun exposure,6 and HIV infection.7 Examining this extensive differential is important when investigating the underlying causes of pompholyx. In our case, the patient has a history of hay fever, indicative of an atopic predisposition. The patch test results were negative, therefore making the likely causes of pompholyx idiopathic. Pompholyx is usually idiopathic in origin. However, a number of contact allergens and drugs are associated with

this disease. Pompholyx can be aggravated by contact with common skin irritants such as water, detergents, and solvents.8 Hyperhidrosis (increased sweating), stress, and smoking can also play an aggravating role.2 Contact allergens that have been recorded to precipitate this condition include anti-wart drugs that contain resorcinol and diphencyprone, cosmetics and hygiene products that contain Balsam of Peru and fragrances, metals such as nickel and cobalt, colostrum that contains chromium from food, compositae plants such as ragweed and Rhus toxicodendron (poison ivy), rubber vulcanizer found in shoes, and sorbic acid found in tobacco powder.2 Drugs that are associated with this disease include highly active antiretroviral therapy (HAART), intravenous immunoglobulins (IVIg), and piroxicam.2 In rare cases, pompholyx can be induced by phototherapy.9 The medical treatment for pompholyx ranges from topical to systemic therapies, and the current best treatment involves a combination of both forms depending on the severity.1 The targets of therapy should be to decrease the formation of vesiculobullous eruptions, reduce inflammation, lessen the sensation of burning and pruritus, prevent sweating, and treat any infections.1,10 Moreover, the patient needs to be advised to avoid aggravating factors such as known allergens and irritants. According to the most recent review article on pompholyx, by Wollina,2 a number of medications and treatments are effective in treating this condition. Even though published evidence is limited, topical corticosteroids are considered to be the cornerstone of treatment in mild cases.2 Other successful topical treatments include calcineurin inhibitors and bexarotene gel. Systemic therapies including corticosteroids, immunosuppressants such as azathioprine, methotrexate, cyclosporine A, and mycophenolate mofetil are used in more severe cases. In addition, alitretinoin, and biologics such as etanercept have been reported to successfully control pompholyx. Antihistamines (such as hydroxyzine, cetirizine, loratadine, terfenadine, dimethindene maleate, desloratadine) could be used to help control the accompanying

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Gill and Pratt pruritus, but scientific evidence for their use is limited. Nickel-sensitive pompholyx has been reported to respond to disodium cromoglycate.5,11 Additional treatment options include botulinum toxin A (BTXA) injections, phototherapy and photochemotherapy, radiotherapy, and tap water ionotrophoresis.2 Infections should also be treated with the appropriate antibiotics or antifungals. The management of pompholyx needs to be targeted to the cause and pathogenesis of the underlying disease. Ideally, there is a need for more controlled trials to be performed and published in order to develop evidence-based guidelines in the management of pompholyx. This is, however, a difficult task, because true cases of pompholyx are rare. Dyshidrotic patterns of hand eczema are much more common, as they are found in 5% to 20% of patients with hand eczema.12 When patients experience a recalcitrant form of pompholyx, a combination of corticosteroids and immunosuppressants is used initially, and it has been proposed that with time patients should switch to immunosuppressants only.2 Mycophenolate mofetil was documented in one case to contribute to pompholyx,13 and the systemic combination of steroids and immunosuppressants such as mycophenolate mofetil has not been evaluated in any controlled trial. In our case, the course of pompholyx is chronic and relapsing. The patient’s disease is approximately 70% better from baseline but certainly not completely controlled. Therefore, patients with this disease should be followed regularly, and treatments may need to be adjusted to successfully control this condition.

Conclusion Pompholyx can be a challenging disease to manage, and treatment can involve an assortment of therapies over a prolonged period of time. Physicians should regularly follow pompholytic cases, as these patients may experience frequent relapses and flare-ups. Fortunately, a case such as ours is extremely rare. This author has had only one case of this severity after 30 years of practice specializing in contact dermatitis and eczematous conditions.

Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

References 1. Wollina U. Pompholyx: what’s new? Expert Opin Investig Drugs. 2008;17:897-904. 2. Wollina U. Pompholyx: a review of clinical features, differential diagnosis, and management. Am J Clin Dermatol. 2010;11:305-314. 3. Lofgran SM, Warshaw EM. Dyshidrosis: epidemiology, clinical characteristics, and therapy. Dermatitis. 2006;17:165181. 4. Alavi A, Skotnicki S, Sussman G, et al. Diagnosis and treatment of hand dermatitis. Adv Skin Wound Care. 2012;25:371-380. 5. Wollina U. Pompholyx or dyshidrosis. Expert Rev Dermatol. 2009;4:403-411. 6. Pitche PT. [Pellagra]. Sante. 2005;15:205-208. 7. MacConnachie AA, Smith CC. Pompholyx as a manifestation of HIV infection, response to antiretroviral therapy. Acta Derm Venereol. 2006;87:378-379. 8. Abramovits W, Goldstein A, Stevenson L. Changing paradigms in dermatology: topical immunomodulators within a permutational paradigm for the treatment of atopic and eczematous dermatitis. Clin Dermatol. 2003;21:383-391. 9. Man I, Ibbotson SH, Fergusan J. Photoinduced pompholyx: a report of 5 cases. J Am Acad Dermatol. 2004;50:55-60. 10. Chen J, Liang YH, Zhou FS, et al. The gene for a rare autosomal dominant form of pompholyx maps to chromosome 18q22.1-18q22.3. J Invest Dermatol. 2006;126:300-304. 11. Wollina U, Naser M. Pharmacoptherapy of pompholyx. Expert Opin Pharmacother. 2004;5:1517-1522. 12. Meding B, Swanbeck G. Epidemiology of different types of hand eczema in an industrial city. Acta Derm Venereol. 1989;69:227-233. 13. Semhoun-Ducloux S, Ducoulx D, Miguet JP. Mycophenolate mofetil-induced dyshidrotic eczema. Ann Intern Med. 2000;132:417.

A Severe Case of Recalcitrant Pompholyx.

Pompholyx is an inflammatory vesiculobullous skin disease of the hands and feet belonging to the spectrum of eczema...
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