Letters

Figure. Clinical Details of the Jarisch-Herxheimer–Like Reaction Observed in Our Study

A Before treatment B 12 Hours after treatment

Inflammatory lesions on the abdomen and forearm of a patient on admission (A) and 12 hours after initiation of terbinafine treatment (B).

observed reaction is also doubtfully drug related, since there and healthy volunteers assessed by conventional and molecular identification were no liver test abnormalities found. The (id) methods. BMC Dermatol. 2014;14:3. reaction was excluded by the following observations: First, 2. Einsiedel L, Gordon DL, Dyer JR. Paradoxical inflammatory reaction during treatment of var. gattii meningitis in an clinical lesions of id reactions are typically intensely pruritic HIV-seronegative woman. Clin Infect Dis. 2004;39(8):e78-e82. and develop quite distantly from the site of infection.6 In the 3. Gryschek RC, Pereira RM, Kono A, et al. Paradoxical reaction to treatment in present case, the patient denied pruritus, and the exacerba- 2 patients with severe acute : a previously unreported tion involved the primary lesions without production of any complication and its management with corticosteroids. Clin Infect Dis. 2010;50 new ones. Second, in id reactions, no fungal forms are recov- (10):e56-e58. ered from the lesions; in the present case, the patient’s le- 4. Nikkels AF, Nikkels-Tassoudji N, Piérard GE. Oral antifungal-exacerbated inflammatory flare-up reactions of dermatomycosis : case reports and review of sions yielded fungal growth. Third, over the course of id re- the literature. Am J Clin Dermatol. 2006;7(5):327-331. actions, no generalized symptoms (eg, fever), as seen in this 5. Belum GR, Belum VR, Chaitanya Arudra SK, Reddy BS. The patient, are normally observed. Jarisch-Herxheimer reaction: revisited. Travel Med Infect Dis. 2013;11(4):231-237. Altogether, this report presents an unusual case of a para- 6. Ilkit M, Durdu M, Karakaş M. Cutaneous id reactions: a comprehensive doxical reaction resembling, to some extent, the JHR, after review of clinical manifestations, epidemiology, etiology, and management. Crit treatment of infection with terbinafine. Rev Microbiol. 2012;38(3):191-202.

Anita Hryncewicz-Gwóźdź, MD, PhD Complete Remission of Squamous Cell Carcinoma Marta Wojciechowska-Zdrojowy, MD, PhD After Treatment With Panitumumab in a Patient Joanna Maj, MD, PhD With Cetuximab-Induced Anaphylaxis Wojciech Baran, MD, PhD A patient with locally advanced cutaneous squamous cell car- Tomasz Jagielski, PhD cinoma (cSCC) who had had an anaphylactic reaction to an epi- dermal growth factor receptor (EGFR) inhibitor, cetuximab,

Author Affiliations: Department of Dermatology, Allergology, and responded to panitumumab. Venereology, Wrocław Medical University, Wrocław, Poland (Hryncewicz- Gwóźdź, Wojciechowska-Zdrojowy, Maj, Baran); Department of Applied Report of a Case | An 89-year-old man presented with a locally ad- Microbiology, Institute of Microbiology, Faculty of Biology, University of vanced cSCC of the nose that was 35 mm in diameter. The exo- Warsaw, Warsaw, Poland (Jagielski). phytic, ulcerated, necrotic tumor invaded local cartilage, but Corresponding Author: Tomasz Jagielski, PhD, Department of Applied Microbiology, Institute of Microbiology, Faculty of Biology, University of there was no metastasis (T4N0M0) (Figure, A). The large size of Warsaw, I. Miecznikowa 1, 02-096 Warsaw, Poland ([email protected]). the lesion and difficulty in repairing the defect after excision Published Online: December 2, 2015. doi:10.1001/jamadermatol.2015.4293. made surgery inappropriate. In addition, the patient’s other co- Conflict of Interest Disclosures: None reported. morbidities precluded general anesthesia. He received radia- 1. Jagielski T, Rup E, Ziółkowska A, Roeske K, Macura AB, Bielecki J. Distribution tion therapy at a dose of 40 Gy in 10 fractions. The tumor of species on the skin of patients with atopic dermatitis, psoriasis, progressed immediately after irradiation with a voluminous

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Figure. Advanced Cutaneous Squamous Cell Carcinoma of the Nose Before and After Panitumumab Monotherapy

A Pretreatment B After irradiation and 30 days C At 6-month follow-up of panitumumab treatment

infiltrated peripheral bulge. Skin biopsy confirmed the per- mumab does not exhibit the α-gal epitope, which explains the sistence of invasive cSCC. Owing to the patient’s age and medi- lower rate of grades 3 and 4 infusion reactions.5 Specific IgE cal history, the multidisciplinary team recommended systemic α-gal antibodies are associated with red meat delayed anaphy- palliative treatment with an EGFR inhibitor (cetuximab, 400 laxis and with cetuximab immediate anaphylaxis.5 A phase 2 mg/m2) beginning 3 months after cessation of the radiation study of panitumumab monotherapy in patients with incur- therapy. The first infusion immediately led to an anaphylac- able cSCC has shown its safety and efficacy.6 tic reaction. Anti-galactose-α-1,3-galactose (α-gal) antibodies These data, as well as the outcome of the present case, were detected. The cetuximab treatment was stopped. suggest that panitumumab is a good alternative to cetux- Treatment with another EGFR inhibitor, panitumumab, imab when anaphylaxis occurs. The overall response rate 6 mg/kg every 14 days, was administered, followed by rapid with panitumumab of 31% (2 of 16 complete responses) in a regression of the peripheral bulge around the ulceration previously extensively pretreated cohort seems to be prom- (Figure, B). After 15 treatment cycles, clinically complete re- ising in cSCC6 and must be confirmed in randomized clinical mission was obtained and biopsies of the remaining ulcer- studies. ation showed only epidermal hyperplasia. Thereafter, pani- tumumab injections were given monthly. After 20 cycles, Aurélie Marti, MS treatment was stopped, and complete remission persisted for Antoine Fauconneau, MD 6 months without any treatment (Figure, C). Nora Ouhabrache, MD Marie Beylot-Barry, MD, PhD Discussion | Managing locally advanced unresectable or meta- Anne Pham-Ledard, MD, PhD static cSCC in elderly patients is a challenge.1,2 Radiotherapy is sometimes inappropriate or ineffective, and platinum- Author Affiliations: Dermatology Department, CHU de Bordeaux, University of based chemotherapy may be given alone or in combination Bordeaux, Bordeaux, France (Marti, Fauconneau, Beylot-Barry, Pham-Ledard); with an EGFR inhibitor.1,2 In elderly patients, an EGFR inhibi- Radiotherapy Department, CHU de Bordeaux, Hôpital Haut Lévêque, Bordeaux France (Ouhabrache). tor as a single-agent therapy has been considered palliative.1,2 Corresponding Author: Anne Pham-Ledard, MD, PhD, Dermatology The EGFR gene codes for a transmembranous tyrosine kinase Department, CHU de Bordeaux, University of Bordeaux, Saint André, receptor responsible for cellular proliferation and epithelial 1 Avenue Jean Burguet 33000 Bordeaux, France growth. Cetuximab, a chimeric monoclonal antibody IgG1 EGFR ([email protected]). inhibitor, was approved for colorectal cancer treatment and Published Online: November 25, 2015. doi:10.1001/jamadermatol.2015.4134. head and neck squamous cell carcinoma and has shown effi- Conflict of Interest Disclosures: None reported. cacy in cSCC in a phase 2 trial3 with a limited number of Additional Contributions: We thank the patient for granting permission to patients. publish this information. Panitumumab is a fully human monoclonal antibody IgG2 1. Jarkowski A III, Hare R, Loud P, et al. Systemic therapy in advanced cutaneous squamous cell carcinoma (CSCC): the Roswell Park experience and a review of EGFR inhibitor indicated for colorectal cancer treatment. It has the literature. Am J Clin Oncol. 2014. doi:10.1097/COC.0000000000000088. shown noninferiority to cetuximab4 and is currently in devel- 2. Stratigos A, Garbe C, Lebbe C, et al; European Dermatology Forum (EDF); opment for head and neck SCC. Panitumumab treatment European Association of Dermato-Oncology (EADO); European Organization consists of 1 infusion every other week vs cetuximab, which for Research and Treatment of Cancer (EORTC). Diagnosis and treatment of is administered weekly. There is also a difference in infusion- invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline. Eur J Cancer. 2015;51(14):1989-2007. related reactions, which occur in less than 0.5% of patients 3. Maubec E, Petrow P, Scheer-Senyarich I, et al. Phase II study of cetuximab as treated with panitumumab vs 2% in those treated with first-line single-drug therapy in patients with unresectable squamous cell 4 cetuximab. This difference in infusion reactions is due to α-gal, carcinoma of the skin. J Clin Oncol. 2011;29(25):3419-3426. a ubiquitous glycan epitope, which is not expressed in humans 4. Price TJ, Peeters M, Kim TW, et al. Panitumumab versus cetuximab in but is present on the Fab portion of cetuximab. Panitu- patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic

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colorectal cancer (ASPECCT): a randomised, multicentre, open-label, tongue with angular fissures (Figure 1). Cardiovascular, non-inferiority phase 3 study. Lancet Oncol. 2014;15(6):569-579. abdominal, and respiratory examination findings were 5. Berg EA, Platts-Mills TA, Commins SP. Drug allergens and food: the normal. cetuximab and galactose-α-1,3-galactose story. Ann Allergy Asthma Immunol. Laboratory tests revealed slight anemia (hemoglobin, 2014;112(2):97-101. 11.4 g/dL; reference range, 12-16 g/dL) and borderline 6. Foote MC, McGrath M, Guminski A, et al. Phase II study of single-agent panitumumab in patients with incurable cutaneous squamous cell carcinoma. increased hemoglobin A1c (5.8%; reference range, 4.0%- Ann Oncol. 2014;25(10):2047-2052. 5.7%). Further evaluation revealed increased levels of gas- trin (129 ng/mL; reference range, 13-115 ng/mL), chromo- Rapid Clearance of Necrolytic Migratory Erythema granin A (223 ng/mL; reference range, 19-98 ng/mL), and Following Intravenous Administration neuron-specific enolase (21.11 ng/mL; reference range, of Amino Acids 0-12 ng/mL). Somatostatin receptor scintigraphy revealed Necrolytic migratory erythema (NME) is a rare paraneoplas- high concentrations of somatostatin receptors in the tic skin disorder, considered the hallmark clinical sign of pancreatic head and adjacent lymph nodes. Computed glucagonoma syndrome. Its recognition allows for early tomography demonstrated an abdominal central tumor in diagnosis of the tumor, which might lead to a better the pancreatic head, medial to the duodenum, causing prognosis.1 Additional mucocutaneous features can include superior mesenteric vein blockage. Endoscopic ultrasono- angular stomatitis and glossitis.2 We present a case of NME graphic examination and needle biopsy showed a neuroen- that cleared rapidly following intravenous administration of docrine tumor, grade 2, and based on findings of immuno- amino acids. histochemical staining (MIB-1 labeling index, 3%) and markedly increased glucagon levels (>500 pmol/L; refer- Report of a Case | A woman in her 50s was evaluated for a per- ence range, <50 to 150 pmol/L) the patient was diagnosed sistent pruritic eruption lasting for 3 months. The eruption with glucagonoma. started on the lower extremities and perianal area and rap- Histopathologic examination of a skin biopsy specimen idly expanded to involve the genital area. Her medical his- from the perianal area showed nonspecific subacute derma- tory included sicca syndrome for the last 20 years. In the titis with mild perivascular lymphocytic infiltrate accompa- last 2 years, the patient had developed angular cheilitis and nied by plasma cells and a few eosinophils. There was no glossitis. She also reported weakness, anorexia, weight evidence of necrolysis in the upper epidermis. loss (approximately 20 kg within a year), numbness and tin- Two weeks after establishing the diagnosis of gluca- gling sensation in the extremities, and instability during gonoma, treatment was initiated with intravenous adminis- walking. tration of a commercial mixture of 500 mL of amino acid so- Physical examination revealed erythematous migratory lution (Vamin 18 electrolyte free; Fresenius Kabi) for 12 hours, plaques with irregular, erosive, scaly borders and hypopig- once a day, for 2 consecutive days. Marked improvement was mented centers on the perianal and genital areas. Licheni- observed after 24 hours, with reduced erythema and scaling, fied erythematous and hyperpigmented plaques were evi- reepithelialization of the erosions in the genital area, and clos- dent on the distal shins. The patient had an erythematous ing of the fissures on the tongue. The skin lesions continued

Figure 1. Pretreatment Clinical Images Illustrating Mucocutaneous Manifestations of Glucagonoma Before Intravenous Amino Acid Infusion

A Tongue B Genitalia

A, Fissured and erythematous tongue. B, Erythematous migratory plaques with irregular, erosive, scaly borders and hypopigmented centers on the genital skin.

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