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Treatment of Refractory Pityriasis Rubra Pilaris with Novel Phosphodiesterase 4

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Treatment of Refractory Pityriasis Rubra Pilaris with Novel Phosphodiesterase 4 Letters Discussion | Acrodermatitis continua of Hallopeau, also Additional Contributions: We thank the patient for granting permission to known as acrodermatitis perstans and dermatitis repens, publish this information. is a rare inflammatory pustular dermatosis of the distal fin- 1. Saunier J, Debarbieux S, Jullien D, Garnier L, Dalle S, Thomas L. Acrodermatitis continua of Hallopeau treated successfully with ustekinumab gers and toes. It is considered a variant of pustular psoriasis and acitretin after failure of tumour necrosis factor blockade and anakinra. or, less commonly, its own pustular psoriasis-like indepen- Dermatology. 2015;230(2):97-100. 1 dent entity. Precise pathophysiology and incidence 2. Kiszewski AE, De Villa D, Scheibel I, Ricachnevsky N. An infant with are unknown. Case literature suggests predominance in acrodermatitis continua of Hallopeau: successful treatment with thalidomide women, but the disease affects both sexes and, rarely, and UVB therapy. Pediatr Dermatol. 2009;26(1):105-106. children.2 3. Jo SJ, Park JY, Yoon HS, Youn JI. Case of acrodermatitis continua accompanied by psoriatic arthritis. J Dermatol. 2006;33(11):787-791. Acrodermatitis continua of Hallopeau initially presents 4. Sehgal VN, Verma P, Sharma S, et al. Acrodermatitis continua of Hallopeau: as erythema overlying the distal digits that evolves into evolution of treatment options. Int J Dermatol. 2011;50(10):1195-1211. pustules.2 The nail bed is often involved, with paronychial 5. Lutz V, Lipsker D. Acitretin- and tumor necrosis factor inhibitor-resistant 3 and subungual involvement and atrophic skin changes. acrodermatitis continua of Hallopeau responsive to the interleukin 1 receptor Most patients experience a chronic, relapsing course involv- antagonist anakinra. Arch Dermatol. 2012;148(3):297-299. ing the proximal digit as the condition worsens.4 Acroder- 6. Iborra M, Beltrán B, Bastida G, Aguas M, Nos P. Infliximab and matitis continua of Hallopeau has been reported to both adalimumab-induced psoriasis in Crohn’s disease: a paradoxical side effect. J Crohns Colitis. 2011;5(2):157-161. evolve into and stem from generalized plaque or pustular psoriasis.3 The present patient was noted to have plaque psoriasis lesions nearly 1 year after the onset of her disease. Treatment of Refractory Pityriasis Rubra Pilaris Psoriatic arthritis is a rare complication,3 but distal phalanx With Novel Phosphodiesterase 4 (PDE4) Inhibitor osteolysis is an important comorbidity.1 Apremilast The differential diagnosis includes infectious paro- Pityriasis rubra pilaris (PRP) is an inflammatory dermato- nychia of viral, fungal, or bacterial etiology, infected contact logic disorder of unknown cause characterized by hyper- dermatitis, and dyshidrotic eczema.4 Gram stain, potassium keratotic follicular papules combining into salmon-colored hydroxide mount, culture, and microscopy may be useful in scaling plaques, palmoplantar hyperkeratosis, and sharply diagnosis. Histopathologically, ACH is characterized by demarcated islands of spared skin.1 We report a case neutrophil-rich spongiform pustules within the epidermis, of refractory PRP treated with the immune modulator dermal edema, and lymphohistiocytosis.4 As in pustular apremilast. psoriasis, biopsy from the nail bed often reveals acanthosis and spongiform pustules.3 Report of a Case | A white man in his 70s presented with an Treatment with topical corticosteroids, tacrolimus, fluo- 8-month history of scaling, pink, pruritic papules, originat- rouracil, calcipotriol, methotrexate, acitretin, cyclosporine, and ing on his back (Figure, A), which coalesced to encompass phototherapy have produced inconsistent responses. Success- nearly his entire body surface. There was extensive ery- ful treatment with tumor necrosis factor inhibitors and the IL-1 thema with scaling and waxy, hyperkeratotic scaling of inhibitor anakinra5 have been reported. However, these agents the palms and soles. are not always efficacious and may even have the potential to A punch biopsy was performed for hematoxylin-eosin incite pustular psoriasis.6 staining and demonstrated alternating parakeratosis and Two cases of ACH treated with concomitant ustekinumab orthokeratosis with spongiosis and mild superficial lympho- and acitretin have been reported, one successfully,1 the other cytic infiltrate. Given these findings, PRP was diagnosed. unsuccessfully.5 The present case is the first to our knowl- The patient started acitretin therapy and showed initial im- edge to be successfully treated with ustekinumab as mono- provement, but after 4 months, his disease continued to prog- therapy. Given that the literature supports ustekinumab as ress. He was transitioned to methotrexate therapy with pred- monotherapy and concomitant therapy for pustular psoria- nisone bridging. However, the methotrexate regimen was sis, ustekinumab was a reasonable choice for our patient and discontinued after 8 weeks owing to lack of response and was succeeded when other agents had failed. replaced with cyclosporine. After 4 weeks of marginal re- sponse with cyclosporine and prednisone, infliximab was Rachel M. Cymerman, BA added, based on literature reports of improvement of PRP with David E. Cohen, MD tumor necrosis factor (TNF) inhibition.2,3 The patient showed marked improvement after 1 inflixi- Author Affiliations: The Ronald O. Perelman Department of Dermatology, mab infusion of 5mg/kg. Unfortunately, 4 weeks later, he was New York University School of Medicine, New York, New York. diagnosed with small-cell lymphocytic leukemia (SLL). Be- Corresponding Author: David E. Cohen, MD, The Ronald O. Perelman cause TNF inhibitors have been associated with an increased Department of Dermatology, New York University School of Medicine, 240 E risk of lymphoma,4 infliximab therapy was discontinued. The 38th St, 11th Floor, New York, NY 10016 ([email protected]). patient sought care for SLL, and rituximab and bendamus- Published Online: November 11, 2015. doi:10.1001/jamadermatol.2015.3444. tine chemotherapy was initiated. After completion of the Conflict of Interest Disclosures: Dr Cohen has consulted for Ferndale, chemotherapy, his PRP worsened. Galderma, and Medimetrics and owns stock or options in Dermira, Topica, and Medimetrics; none of these companies had any role in the present article. No The challenge was to identify a PRP-directed treatment other disclosures are reported. in a patient with refractory disease and contraindication to 348 JAMA Dermatology March 2016 Volume 152, Number 3 (Reprinted) jamadermatology.com Copyright 2016 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Letters Figure. A Case of Refractory Pityriasis Rubra Pilaris Before and After 8 Months of Apremilast Therapy A Before treatment B After 8 months of treatment Almost complete resolution is seen on the back of this elderly male patient. TNF inhibitors. After exhausting therapeutic options, we TNF inhibition, the choice of apremilast was a logical next considered apremilast (Otezla; Celgene Corporation). The step for the patient in the present case. The drug is appeal- patient started with a dose of 10 mg/d and titrated over ing owing to its minimal adverse effects and monitoring 5 days to the recommended maintenance dose of 30 mg requirements.6 At 12-month follow-up, the patient twice daily. remained disease free. Four weeks later, the patient reported significant Our experience suggests that apremilast may be an improvement in symptoms. He complained of mild gastro- effective treatment for refractory PRP. Additional studies intestinal upset but denied other new symptoms. The most are necessary to further establish the role of PDE4 inhibitors common adverse effects reported with apremilast are diar- as an option for refractory PRP. rhea, nausea, and headache.5 At 8- and 12-week follow-ups, he reported further decreases in body surface area involve- Ifat Zerin Krase, PharmD ment of PRP. At 6- and 8-month follow-ups, he showed Kevin Cavanaugh, MD nearly complete resolution of skin findings (Figure, B). Clara Curiel-Lewandrowski, MD Discussion | There is no unifying etiology to the pathogenesis Author Affiliations: University of Arizona College of Medicine, Tucson (Krase); Department of Dermatology, University of Arizona, Tucson (Cavanaugh, of PRP. Current treatments are mainly empirical or based on Curiel-Lewandrowski). case reports. Systemic retinoids and methotrexate are often Corresponding Author: Clara Curiel-Lewandrowski, MD, Department of used as first-line treatments. Other therapies include aza- Dermatology, University of Arizona, 1501 N Campbell Ave, Tucson, AZ 85724 thioprine, cyclosporine, fumaric acid, mycophenolate ([email protected]). mofetil, vitamin D analogues, and phototherapy.1,2 Published Online: November 4, 2015. doi:10.1001/jamadermatol.2015.3405. Eastham et al3 demonstrated, in the most comprehen- Conflict of Interest Disclosures: None reported. sive analysis to date, that TNF inhibition is effective for re- Additional Contributions: We are indebted to Fangru Lian, MD, Department of fractory PRP. The patient in the present case responded well Pathology, University of Arizona, Tucson, for providing the histopathologic to infliximab but could not continue therapy because he analysis for the case. She did not receive any compensation for her developed SLL. Based on the proposed immune-driven contributions. mechanism of PRP, we explored novel treatments targeting 1. Klein A, Landthaler M, Karrer
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