204 Correspondence 7 Zhu KJ, Zhu CY, Fan YM. Alcohol consumption and psoriasis risk: a meta-analysis of case–control studies. J Dermatol 2012; 39:770–3. 8 Towne JE, Renshaw BR, Douangpanya J et al. Interleukin-36 (IL36) ligands require processing for full agonist (IL-36a, IL-36 b, and IL-36c) or antagonist (IL-36Ra) activity. J Biol Chem 2011; 286:42594–602. Funding sources: none. Conflicts of interest: R.M. and M.P.S. have received payments for conduction of clinical trials, as invited speaker or advisor, or for travel grants from the following companies: Abbott GmbH & Co. KG, Biogen IDEC GmbH, Essex Pharma GmbH, Janssen-Cilag, LEO Pharma GmbH, Merck Serono GmbH, Novartis Pharma GmbH, Pfizer GmbH and Wyeth Pharma GmbH. M.P.S. has received research grants from Abbott and BiogenIdec, and has received consulting fees from Abbott, BiogenIdec, Janssen-Cilag, LEO Pharma, Novartis Pharma and Pfizer.

A case of CD8+ small/medium-sized pleomorphic T-cell lymphoma: clinical and histopathological differential diagnosis DOI: 10.1111/bjd.12549 DEAR EDITOR, CD8+ lymphoid proliferation is a rare type of cutaneous T-cell lymphoma.1 Recently, CD8+ lymphoid proliferations that usually present with solitary, slow-growing nodules on the face or ear, and which resolve after treatment, have raised the possibility of a distinct entity, although the prognostic influence of the CD8 phenotype is still unclear. Irrespective of the histopathological appearance suggesting a high-grade lymphoma in some cases, clinical behaviour should be the main basis for the determination of treatment.2,3 A 60-year-old female patient was admitted with the complaint of progressively increasing red and swollen lesions on her face. Histopathological examination of the initial biopsy, performed 6 years previously, had been compatible with rosacea; a partial regression occurred with rosacea treatments. However, more prominent lesions recurred at almost the same (a)

(b)

sites after nearly 1 year. A second biopsy exhibited ‘perifollicular lymphoid infiltration’. The patient had no drug history. A partial regression has been noticed with intralesional steroid injections. Dome-shaped, discrete nodules, bright pink in colour, involved the forehead, nasolabial folds and cheeks – prominently confined to sun-exposed areas (Fig. 1). The main characteristics of the clinical picture suggested a photoinduced dermatosis. Our first skin biopsy was interpreted as ‘cutaneous lymphoproliferative lesion with CD8+ cytotoxic phenotype’. Peripheral T-cell lymphoma and actinic reticuloid were proposed in the differential diagnosis. We did not detect the characteristic photosensitivity when applying photopatch test using ultraviolet (UV) A and UVB. There was partly diffuse or patchy infiltration within the dermis and subcutaneous fatty tissue, composed of small-to-medium-sized lymphoid cells with oval or round nuclei, dark chromatin and scant cytoplasm. The epidermis was spared and a subepidermal Grenz zone was prominent in the upper dermis. All T cells were CD3+, CD2+, CD5+ and CD8+. While immunoreactivity with granzyme-B and TIA-1 was identified in most of the lymphoid cells, they were negative for CD4, CD7 and CD56. The proliferative activity with Ki67 was 5% (Fig. 2). A clonal T-cell population was not encountered using BIOMED 2 (http://cordis.europa.eu/ biomed/). The patient was investigated for systemic involvement. b2Microglobulin was 1
749 mg L 1; human immunodeficiency virus was negative; other biochemical tests, and thoracal and neck tomography scans were normal. There was no association with Epstein–Barr virus. Using flow cytometry, the cell count was very low; in CD45/side scatter graphs, the percentages of lymphocyte, granulocyte, monocyte and CD45– cells were 23%, 69%, 5% and 2%, respectively; in forward scatter/side scatter graphs, the percentage of T lymphocytes was 66%. There was an increase (36–37%) of natural killer cells and the ratio of CD4+/CD8+ T lymphocytes was normal. Topical steroid and retinoid–psoralen plus UVA (PUVA) provided a remarkable resolution of lesions after 4 weeks. Because new formation of infiltrated papular lesions was

(c)

Fig 1. (a) Firm, pinky-red, shiny, hemispherical, infiltrative papules and nodules located on the forehead; (b) infiltrative papules and nodules restricted to sun-exposed areas are noteworthy; (c) almost complete response after treatment, with residual grouped papules. British Journal of Dermatology (2014) 170, pp200–227

© 2013 British Association of Dermatologists

Correspondence 205

(a)

(b)

(d)

(h)

(e) (i)

(f) (c)

(j) (g)

Fig 2. (a, b) Diffuse infiltration within the dermis, extending to the subcutaneous fatty tissue, with a Grenz zone beneath the epidermis; (c) infiltration is composed of small-to-medium-sized lymphoid cells with oval or round nuclei, dark chromatin and scant cytoplasm. Haematoxylin and eosin staining; original magnification: (a) 9 40; (b) 9 200; (c) 9 1000. Tumour cells were (d) CD3+, (e) CD5+, (f) CD8+, (g) TIA-1+, (h) CD20– and (i) CD4 . (j) Using Ki67, proliferative activity was < 5%; original magnification: 9 400.

detected, the retinoid was stopped and a combination therapy of PUVA plus methotrexate 25 mg weekly and subcutaneous interferon alfa-2b, 3 9 4
5 mU weekly was started. After the application of 30 sessions of PUVA and five weekly doses of methotrexate, and 15 doses of interferon alfa-2b, we did not observe enough regression. Therefore, all the treatment modalities were stopped and the application of 18 sessions of radiotherapy alone using 6 mV energy with 17 9 180 Gy provided complete healing, and the patient was in full recovery after 1 year. The most prominent clinical feature of the present case is the localization of the lesions, suggesting a UV-induced skin disorder. But the clinical features did not indicate actinic reticuloid, granulomatous rosacea or sarcoidosis, which were proposed as the preliminary diagnoses. Mycosis fungoides was also considered because lesions were slowly progressing and histopathological examination showed T-cell phenotypes. However, the absence of epidermotropism or folliculotropism, the presence of CD8+ T cells and the clinical findings excluded the probability of mycosis fungoides. Certain cases do not meet the enrolment criteria for the general classification of primary cutaneous T-cell lymphomas. Some of these have been termed ‘peripheral T-cell lymphoma, unspecified type’. This group generally follows an aggressive course and primary cutaneous CD8+ T-cell lymphomas localized to the ear, nose and, rarely, the face are included in this group.4–8 The cases termed CD8+ T-cell lymphoma of the ear by Petrella et al.7 have been reported to follow an indolent course. While most cases present with solitary nodules on the head or neck,9 the present case had multiple nodules involving the © 2013 British Association of Dermatologists

whole face. Khamaysi et al.10 described a case with a pruritic nodule on the patient’s right foot as pleomorphic CD8+ small/medium size cutaneous T-cell lymphoma. Similarly, Kempf et al.3 published three cases with the same lymphoproliferations in the skin at extrafacial sites. These cases were similar to our case in clinical progress but with different localizations; the lesions were totally cured with radiotherapy. The primary cutaneous cytotoxic T-cell lymphoma with small-to-medium-sized cells, and its slowly progressive course with the absence of epidermotropism should constitute a different group of T-cell lymphomas from a prognostic point of view. There are some primary cutaneous lymphomas with interesting features that do not completely fit into the classification from the aspect of clinical presentation, course, histopathological and immunophenotypic features. We suggest nonaggressive treatment strategies for such lymphoproliferative lesions. Departments of 1Dermatology, and 2 Pathology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey E-mail: [email protected]

Z. KUTLUBAY1 B. ENGIN1 E. KOTE1 O. AYDIN2 C. DEMIRKESEN2 O. OGUZ1

References 1 Dummer R, Kamarashev J, Kempf W. et al. Junctional CD8+ cutaneous lymphomas with nonaggressive clinical behaviour. Arch Dermatol 2002; 138:199–203. British Journal of Dermatology (2014) 170, pp200–227

206 Correspondence 2 Lu D, Patel KA, Duvic M, Jones D. Clinical and pathological spectrum of CD8-positive cutaneous T-cell lymphomas. J Cutan Pathol 2002; 29:465–72. 3 Kempf W, Kazakov DV, Cozzio A et al. Primary cutaneous CD8 (+) small-to medium-sized lymphoproliferative disorder in extrafacial sites: clinicopathologic features and concept on their classification. Am J Dermatopathol 2013; 35:159–66. 4 Beltraminelli H, M€ ullegger R, Cerroni L. Indolent CD8+ lymphoid proliferation of the ear: a phenotypic variant of the smallmedium pleomorphic cutaneous T-cell lymphoma? J Cutan Pathol 2010; 37:81–4. 5 Suchak R, O’Connor S, McNamara C, Robson A. Indolent CD8positive lymphoid proliferation on the face: part of the spectrum of primary cutaneous small-/medium-sized pleomorphic T-cell lymphoma or a distinct entity? J Cutan Pathol 2010; 37:977–81. 6 Li XQ, Zhou XY, Sheng WQ et al. Indolent CD8+ lymphoid proliferation of the ear: a new entity and possible occurrence of signet ring cells. Histopathology 2009; 55:468–70. 7 Petrella T, Maubec E, Cornillet-Lefebvre P et al. Indolent CD8positive lymphoid proliferation of the ear: a distinct primary cutaneous T-cell lymphoma? Am J Surg Pathol 2007; 31:1887–92. 8 Swick BL, Baum CL, Venkat AP, Liu V. Indolent CD8+ lymphoid proliferation of the ear: report of two cases and review of the literature. J Cutan Pathol 2011; 38:209–15. 9 Leinweber B, Beltraminelli H, Kerl H, Cerroni L. Solitary smallto-medium-sized pleomorphic T-cell nodules of undetermined significance: clinical, histopathological, immunohistochemical and molecular analysis of 26 cases. Dermatology 2009; 219:42–7. 10 Khamaysi Z, Ben-Arieh Y, Epelbaum R, Bergman R. Pleomorphic CD8+ small/medium size cutaneous T-cell lymphoma. Am J Dermatopathol 2006; 28:434–7. Funding sources: none. Conflicts of interest: none declared.

Development of chronic inflammatory demyelinating polyneuropathy in a patient receiving infliximab for psoriasis DOI: 10.1111/bjd.12572 DEAR EDITOR, A 49-year-old white man was referred to the Manchester Psoriasis Service with a 21-year history of severe chronic plaque psoriasis refractory to therapy with topical agents, phototherapy (TL-01), systemic agents (methotrexate, ciclosporin and fumaderm) and the biologic agents adalimumab and ustekinumab, including with concurrent ciclosporin therapy. Relevant history included alcohol excess. There was no family history of demyelination. Following a flare of psoriasis in June 2011, treatment was changed from ustekinumab (90 mg dosing regimen) with ciclosporin 2 mg kg 1 daily, to infliximab intravenously (5 mg kg 1 at weeks 0, 2 and 6, and thereafter at 8-week intervals). On initiation of infliximab, ciclosporin was discontinued but reintroduced at 2 mg kg 1 daily due to a flare in December 2011. Two weeks later, the patient reported sudden onset of weakness of his right hand and numbness of the fingertips bilaterBritish Journal of Dermatology (2014) 170, pp200–227

ally. With no objective sensory disturbance and unilateral right upper limb weakness, urgent assessment by a neurologist led to a provisional diagnosis of brachial plexopathy secondary to ciclosporin, which was stopped. Due to the severity of the patient’s psoriasis, infliximab therapy was continued. During January 2012 he reported worsening of sensory disturbance in the arms and new weakness in both legs. Neurological examination revealed reduced tone in the right upper limb, right forearm muscle wasting, right hand weakness in an ulnar and median nerve distribution. Reflexes were present in both arms with no sensory loss. The lower limbs had normal tone. Mild bilateral dorsiflexion weakness was noted. Sensation was normal; all reflexes were absent. Urgent investigations included magnetic resonance imaging of the brain and cervical spine, which was normal. Nerve conduction studies revealed changes compatible with a primary demyelinating neuropathy and met diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP). Cerebral spinal fluid findings demonstrated no pleocytosis or oligoclonal bands, protein and glucose were within normal parameters; nerve biopsy was not performed. With a working diagnosis of infliximab-associated CIDP, infliximab therapy was discontinued in February 2012 and ciclosporin reinstituted. The patient’s neurological condition deteriorated 3 months from onset of symptoms with marked global limb weakness with distal bias, sensory ataxia and severe neuropathic pain of the feet. Treatment with intravenous immunoglobulin (IVIg) was commenced [150 g over 5 days (0
4 mg kg 1)], with a second course a month later followed by concomitant oral prednisolone (40 mg daily) after 8 weeks, which resulted in a significant worsening of his condition. Clinical stabilization was achieved with a course of plasma exchange and continued monthly pulses of IVIg. One year after the initial onset of symptoms the patient’s distal limb power has improved, he is able to mobilize with a stick but continues to be profoundly sensory ataxic and IVIg dependent. Following withdrawal of infliximab, the patient’s psoriasis flared and now requires combination treatment with Fumadermâ (Almirall Hermal, Reinbek, Germany) 240 mg three times daily, acitretin 50 mg daily and ciclosporin 50 mg twice daily. CIDP is an acquired demyelinating disease of the peripheral nervous system. It typically presents between the ages of 30 and 60 years and is characterized by progressive symmetrical proximal and distal muscle weakness, sensory dysfunction and impaired balance.1 The course of the disease can be monophasic, relapsing and remitting or progressive.1 Various diagnostic criteria exist, utilizing findings from clinical, electrophysiological and laboratory testing.2 Because demyelination in CIDP is multifocal, clinical and pathological manifestations vary. The reported prevalence of 1–7
7 per 100 000 in Northern Europe3 may be an underestimation due to difficulty in the identification of ‘atypical’ cases.3 The exact triggers for CIDP are unknown. A number of disorders are associated with CIDP including organ transplantation, inflammatory bowel disease, diabetes, and malignant © 2013 British Association of Dermatologists