Dlo150003.Pdf

Letters described in the Japanese population, several PP cases have 6. Valkenborgh T, Bral P. Starvation-induced ketoacidosis in bariatric surgery: also been reported in Western countries and, recently, in the a case report. Acta Anaesthesiol Belg. 2013;64(3):115-117. Middle East.2,3 The pathogenesis of PP is not completely clear. In addition Occurrence of Psoriasiform Eruption to being associated with several factors including exogenous During Nivolumab Therapy for Primary (physical trauma, friction) and hormonal (pregnancy,menstrua- Oral Mucosal Melanoma tion), PP has classically been reported in association with meta- The immunoinhibitory receptor programmed death 1 (PD-1) is bolic derangements, especially ketotic states (dieting, fasting, expressed on antigen-stimulated T cells. The interaction be- diabetes mellitus).2,3 Actually, several studies have detected el- tween PD-1 and its ligands, which are expressed on dendritic evated urine and/or blood ketone levels in patients with PP.2,3 cells, macrophages, and cancer cells, inhibits antitumor ac- In such circumstances, it is believed that ketone bodies may dis- tivity of cytotoxic T cells.1 A fully human anti–PD-1 antibody, tribute around blood vessels leading to perivascular inflamma- nivolumab, has been approved in Japan for unresectable mela- tion or enter into cells modifying their intracytoplasmic pro- noma. We report a case of melanoma that responded well to cesses. The inflammation is believed to be mainly mediated by nivolumab treatment, but the patient developed skin erup- neutrophils: PP usually responds well to medications with an- tions resembling psoriasis. tineutrophil effect, such as dapsone and tetracyclines, which would support this neutrophil-mediated theory. A role for de- Report of a Case | An 80-year-old man had been receiving niv- creased insulin levels, which is reported to occur after bariat- olumab therapy at 2 mg/kg every 3 weeks at another hospital ric surgery,4 has also been hypothesized as cause of PP.2 to treat unresectable primary mucosal melanoma presenting In addition to its effect in changing the course of many skin on the upper lip, palate, and cheeks (Figure 1A).Priortothe diseases such as psoriasis, bariatric surgery has been associ- therapy, he had no metastatic disease. He was previously ated with several dermatoses including bowel-associated der- healthy without personal or family history of psoriasis. The tu- matosis–arthritis syndrome, nutritional deficiency dermato- mor on the lip enlarged over the course of the first 2 doses of ses, and alopecia.5 However, PP has never been reported after nivolumab and then began to shrink after the third dose. Im- bariatric surgery. Given that such surgery may easily repli- mediately following the fourth dose, the patient developed cate the metabolic disturbance associated with other ketotic malaise, skin eruption, dysesthesia, and severe pain of the ex- states such as dieting or fasting,5,6 we believe that the asso- tremities. He was therefore referred to our hospital for evalu- ciation between PP and bariatric surgery may be underdiag- ation of his systemic condition. nosed or underreported. On admission, he had a low-grade fever, and the nodule on In conclusion, to our knowledge, this report is the first to his lip was markedly reduced in size (Figure 1B). He had no gas- describe PP developing after bariatric surgery, adding PP to the trointestinal symptoms, and computed tomographic scans cutaneous complications of such procedures. Increased aware- showed no metastatic lesions or interstitial pneumonia. Find- ness of this rare entity and this association is important be- ings from neurological examination were unremarkable. Skin cause bariatric surgery is a common procedure nowadays, and examination revealed asymptomatic, sharply bordered, scaly, the metabolic abnormalities accompanying it mimic those that erythematous plaques on the trunk and extremities, but erup- occur with other ketotic states. tions having unclear borders or crusts were also seen (Figure 1C). Routine laboratory test results were normal except for Mustafa Abbass, MS highly elevated C-reactive protein (CRP) (11.2 mg/dL; normal Firass Abiad, MD range <0.3 mg/dL). A skin biopsy performed on the day of ad- Ossama Abbas, MD mission revealed mild parakeratotic hyperkeratosis, irregular acanthosis, and moderate infiltration of mononuclear cells in Author Affiliations: American University of Beirut Medical Center, Beirut, the dermis (Figure 2). Some of the infiltrates tested positive Lebanon. for interleukin (IL)-17 or IL-23 by immunohistochemical analy- Corresponding Author: Ossama Abbas, MD, Department of Dermatology, sis. The granular layer was absent in most areas. American University of Beirut Medical Center, Riad El Solh/Beirut 1107 2020, Beirut, Lebanon, PO Box 11-0236 ([email protected]). On the third day after hospitalization, the patient devel- Published Online: April 8, 2015. doi:10.1001/jamadermatol.2015.0247. oped a high fever, over 39.5°C. He was prescribed oral pred- Conflict of Interest Disclosures: None reported. nisolone (0.7 mg/kg), and the systemic symptoms and skin 1. Nagashima M, Ohshiro A, Shimizu N. A peculiar dermatosis with gross eruptions improved immediately. After termination of pred- reticular pigmentation [in Japanese]. Japanese J Dermatol. 1971;81:78-91. nisolone treatment, the eruptions recurred along with in- 2. Böer A, Misago N, Wolter M, Kiryu H, Wang XD, Ackerman AB. Prurigo creased CRP levels and a fever up to 37.8°C. Readministration pigmentosa: a distinctive inflammatory disease of the skin. Am J Dermatopathol. of prednisolone (0.4 mg/kg) immediately resolved these symp- 2003;25(2):117-129. toms, and at last follow-up he was taking 0.1 mg/kg of pred- 3. Oh YJ, Lee MH. Prurigo pigmentosa: a clinicopathologic study of 16 cases. nisolone. During the 3 months after the last dose of niv- J Eur Acad Dermatol Venereol. 2012;26(9):1149-1153. olumab, the lesions on the palate decreased in size. No 4. Jacobsen SH, Olesen SC, Dirksen C, et al. Changes in gastrointestinal melanoma cells were found in the biopsy from the upper lip. hormone responses, insulin sensitivity, and beta-cell function within 2 weeks after gastric bypass in non-diabetic subjects. Obes Surg. 2012;22(7):1084-1096. 5. Halawi A, Abiad F, Abbas O. Bariatric surgery and its effects on the skin and Discussion | Previous clinical trials of anti–PD-1 antibody have skin diseases. Obes Surg. 2013;23(3):408-413. demonstrated a potent antitumor activity for metastatic jamadermatology.com (Reprinted) JAMA Dermatology July 2015 Volume 151, Number 7 797 Copyright 2015 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 Letters Figure 1. Clinical Features of the Present Case Figure 2. Skin Biopsy Specimen From a Plaque Lesion on the Forearm A Upper lip before nivolumab treatment Parakeratotic hyperkeratosis, irregular elongation of the epidermal rete ridge, and mononuclear cell infiltration in the dermis are seen. Infiltration of neutrophils and eosinophils are not present (hematoxylin-eosin, original magnification ×200). B Upper lip after fourth nivolumab cycle melanoma.2,3 Approximately one-third of the patients showed regression of their lesions.2 Adverse events, most of which were mild to moderate, were observed in more than 80% of all patients. Cutaneous adverse events occurred in about half of the patients, which were categorized as rash, vitiligo, pruritus, and acneiform eruptions.2,3 Our patient developed skin eruptions mimicking psoriasis, which has not been noted in previous reports to our knowledge. Psoriasis or psoriasiform eruption is well known to occur as a paradoxical reaction during biological therapies for severe psoriasis. This phenomenon is thought to be mediated by the increased production of interferons.4 Previous studies have demonstrated that blockade of the immune-checkpoint receptors, such as PD-1 and cytotoxic T-lymphocyte antigen-4, by its an- tibodies augmented the helper T cell type 1 (TH1) and TH17 cell activities, which might correlate with antitumor effect.5,6 The occurrence of the psoriasiform eruptions and systemic illness temporally coincided with the regression of melanoma lesions, suggesting strong correlation with nivolumab’s mechanism of C Arm after fourth nivolumab cycle action. Therefore, psoriasiform eruptions may be induced in cases of sufficient nivolumab antitumor efficacy. Further inves- tigations are needed to clarify the relation between the cutaneous adverse events and antitumor activity of nivolumab. Mikio Ohtsuka, MD Takako Miura, MD Tatsuhiko Mori, MD Masato Ishikawa, MD Toshiyuki Yamamoto, MD Author Affiliations: Department of Dermatology, Fukushima Medical University School of Medicine, Fukushima, Japan. Corresponding Author: Mikio Ohtsuka, MD, Department of Dermatology, A, A red, partially blackish nodule is present on the upper lip. B, After Fukushima Medical University School of Medicine, Hikarigaoka-1, Fukushima, nivolumab, the nodule on the lip is significantly smaller. C, Well-demarcated, 960-1295, Japan ([email protected]). scaly, erythematous plaques are observed on the arm; eruptions show unclear Published Online: April 15, 2015. doi:10.1001/jamadermatol.2015.0249. borders or crusts. Conflict of Interest Disclosures: None reported. 798 JAMA Dermatology July 2015 Volume 151, Number 7 (Reprinted) jamadermatology.com Copyright 2015 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/

Load more