538 Correspondence
Before therapy 100·00
**
After therapy
*
**
**
Score
80·00
Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan E-mail: [email protected]
60·00 40·00
References
20·00
ng
ns ct io
ni
m ot io
-F un
-E
x1 6
x1 6 Sk in
de
de Sk in
Sk in
de
x1 6
-S
de
x1 6
ym pt om s
-T ot al
0·00
Sk in
A. FUKUNAGA M. HATAKEYAMA M. TSUJIMOTO Y. ODA K. WASHIO C. NISHIGORI
Fig 1. Mean Skindex-16 subscale scores before and after steroid pulse therapy (*P < 0001, **P < 00001).
The mean total, symptoms, emotions and functioning scores before therapy were 705 88, 571 155, 792 72 and 690 72, respectively. Notably, the mean total and functioning scores before therapy in patients with AIGA were higher than those for other skin diseases including severe atopic dermatitis (total 606, functioning 412),6 severe psoriasis (total 537, functioning 405)7 and nonmelanoma skin cancer (functioning 121–151).5 All of the scores significantly improved after steroid pulse therapy (Fig. 1). In contrast, the total score for the patient who did not receive steroid pulse therapy (patient 2) was not significantly improved (change from 845 to 770) in the 6 months of follow-up. Similarly to previous reports, our study revealed that only two of eight patients with AIGA had sweat allergy detected by histamine release test on sweat or skin test using autologous sweat, suggesting that sweat allergy is not involved in the pathogenesis of AIGA.8,9 Steroid pulse therapy can generally improve the symptoms of AIGA.1,10 Only a few reports have documented the efficacy of pulse therapy. This report revealed that steroid pulse therapy alleviated the anhidrosis of all eight patients with AIGA, and adverse effects were not observed during follow-up. Symptomatic improvement was not observed in the patient who did not receive steroid pulse therapy. Moreover, symptomatic improvement was clearly linked to improved QoL. Notably, untreated AIGA was associated with considerably reduced QoL; the impact of AIGA on QoL was greater than that of other skin diseases. These observations suggest that steroid pulse therapy should be recommended as a standard therapy for patients with AIGA. This is the first report examining QoL in AIGA. Consideration of QoL in patients with AIGA is important in the assessment of suitable treatment. British Journal of Dermatology (2015) 172, pp537–547
1 Fukunaga A, Horikawa T, Sato M, Nishigori C. Acquired idiopathic generalized anhidrosis: possible pathogenic role of mast cells. Br J Dermatol 2009; 160:1337–40. 2 Kozaru T, Fukunaga A, Taguchi K et al. Rapid desensitization with autologous sweat in cholinergic urticaria. Allergol Int 2011; 60:277–81. 3 Fukunaga A, Bito T, Tsuru K et al. Responsiveness to autologous sweat and serum in cholinergic urticaria classifies its clinical subtypes. J Allergy Clin Immunol 2005; 116:397–402. 4 Higaki Y, Kawamoto K, Kamo T et al. The Japanese version of Skindex-16: a brief quality-of-life measure for patients with skin diseases. J Dermatol 2002; 29:693–8. 5 Chren MM, Sahay AP, Bertenthal DS et al. Quality-of-life outcomes of treatments for cutaneous basal cell carcinoma and squamous cell carcinoma. J Invest Dermatol 2007; 127:1351–7. 6 Kawashima M, Harada S. Effect of standard medication on quality of life of patients with atopic dermatitis. J Dermatol 2007; 34:9–16. 7 Okubo Y, Natsume S, Usui K et al. Low-dose, short-term ciclosporin (Neoralâ) therapy is effective in improving patients’ quality of life as assessed by Skindex-16 and GHQ-28 in mild to severe psoriasis patients. J Dermatol 2011; 38:465–72. 8 Nakamizo S, Egawa G, Miyachi Y, Kabashima K. Cholinergic urticaria: pathogenesis-based categorization and its treatment options. J Eur Acad Dermatol Venereol 2012; 26:114–16. 9 Sawada Y, Nakamura M, Bito T et al. Decreased expression of acetylcholine esterase in cholinergic urticaria with hypohidrosis or anhidrosis. J Invest Dermatol 2014; 134:276–9. 10 Ohshima Y, Yanagishita T, Ito K et al. Treatment of patients with acquired idiopathic generalized anhidrosis. Br J Dermatol 2013; 168:430–2. Funding sources: none. Conflicts of interest: none declared.
Intractable erosive lichen planus treated successfully with rituximab DOI: 10.1111/bjd.13537 DEAR EDITOR, Erosive lichen planus (LP) is a chronic recurrent disease manifesting as erosive ulcers affecting oral and genital mucosa.1,2 It can also affect oesophageal, lacrimal, conjunctival and laryngeal mucosa. High-potency topical corticosteroids are the first-line treatment; however, monotherapy is rarely successful. Alternatives include systemic corticosteroids, immunosuppressants and retinoids; however, the side-effects carry a significant morbidity. © 2014 British Association of Dermatologists
Correspondence 539
In recalcitrant cases, biological agents, including etanercept, adalimumab, infliximab, efalizumab, basiliximab and alefacept, have been used with some success.3 Parmentier et al. reported a case of mucocutaneous LP successfully treated with four intravenous courses (375 mg m 2) of rituximab at weekly intervals (lymphoma protocol).1 We report two cases of vulvovaginal gingival LP achieving remission with rituximab. The first case is that of a 46-year-old woman with a 6-month history of oral and vulvovaginal symptoms, including severe erosive vulvovaginitis and gingivitis. The diagnosis was confirmed by histopathology (Fig. 1). Aural symptoms comprised thickened inflamed tympanic membrane and auditory canal. Ophthalmological manifestations incorporated epiphoria and inflamed, stenosed lacrimal ducts. Past history included joint sarcoidosis. Initial treatment with topical superpotent steroid and tacrolimus yielded only a partial response. Courses of oral prednisolone did not achieve symptom control. Despite treatment with mycophenolate mofetil, symptoms persisted. Severe dysphagia restricted oral intake. Infliximab was commenced, producing a prompt response. Adalimumab was initiated as maintenance therapy. Remission lasted 18 months and prednisolone was tapered to 75 mg. Vaginal dilatation under anaesthesia was performed. Relapse of severe dysphagia and vulvovaginal symptoms occurred (Fig. 2a). Prednisolone 20 mg was started, adalimumab discontinued and infliximab restarted, but, on this occasion, it proved ineffective. Rituximab (1 g) on days 1 and 15 was commenced. Remission was achieved within 4 weeks of completion of infusion. Prednisolone was tapered by 5 mg weekly to a maintenance dose of 5 mg. Remission lasted 8 months (Fig. 2b). Relapse necessitated a course of prednisolone (20 mg), which was tapered by 5 mg every month to a maintenance dose of 5 mg. Relapses were treated with repeat infusions. Three infusions of 1 g each at approximately 5-
month intervals were given. Unfortunately, 14 months after the commencement of rituximab, breast carcinoma with spinal metastasis was diagnosed, and further rituximab was contraindicated. Current control is with short courses of oral prednisolone, topical clobetasol and interval vaginal and oesphageal dilatation. The second case is that of a 40-year-old woman with a 3-year history of oral LP. Initial treatment by an oral medicine physician included intralesional triamcinolone and steroid mouthwashes. Vulvovaginal symptoms and cutaneous involvement at the scalp and lower limbs developed. Dermatological opinion was sought, and histopathology from the vulva and foot confirmed LP. In this case, the disease was initially responsive to topical clobetasol but became recalcitrant. Colposcopy and vaginal dilatation were performed. Oral steroids were discontinued secondary to severe insomnia, hallucinations and mood swings. Mycophenolate mofetil was commenced but drug hypersensitivity developed. Rituximab (1 g) on days 1 and 15 was commenced. Remission was achieved within 4 weeks of treatment. A prophylactic dose of 1 g was given 5 months later. At the last follow-up, complete remission was maintained 8 months after the last infusion. Rituximab is chimeric murine–human monoclonal CD20 antibody approved for rheumatoid arthritis (RA), B-cell lymphomas and vasculitis.4 The mechanism of action includes antibody-dependent cytotoxicity, complement-mediated lysis,
(a)
(b)
Fig 1. Skin biopsy from vulva. Haematoxylin and eosin staining showing typical features of erosive lichen planus, including thinned epidermis with subepidermal hyalinization and deeper inflammatory infiltrate. © 2014 British Association of Dermatologists
Fig 2. (a) Severe erosive gingivitis of lower gingiva. (b) Normalappearing gingiva exhibiting remission of gingivitis. British Journal of Dermatology (2015) 172, pp537–547
540 Correspondence
direct disruption of signalling pathways and triggering of apoptosis.4 Off-label uses include pemphigus vulgaris (PV), mucosal membrane pemphigoid,5,6 paraneoplastic pemphigus and chronic graft-versus-host disease.4 Mucosal membrane diseases can be devastatingly destructive and in some cases fatal.5,6 PV of the epiglottis treated with rituximab was recently reported.7 The mechanism by which rituximab improves T cell-mediated LP is difficult to explain as it suggests B cells are implicated in the pathogenesis of LP. The majority of intraepithelial lymphocytes in oral LP are CD8+ cytotoxic T cells, but most lymphocytes in the lamina propria are CD4+ helper T (Th) cells. CD8+ cytotoxic T cells may be activated by the combination of antigen associated with major histocompatibility complex class I on basal keratinocytes and Th1 CD4+ T cellderived interleukin (IL)-2 and interferon-c.1,2 In RA, Melet et al. found rituximab caused a durable, reversible depletion of peripheral CD4+ and CD8+ T cells.8 Rituximab efficacy in PV is probably due to B-cell depletion resulting in decreased desmoglein (Dsg)-specific autoantibodies. PV pathogenesis likely involves both autoreactive Th1 and Th2 cells to promote autoantibody secretion by Dsg3-reactive B cells.9 Dsg3-specific T cells have also been demonstrated to release IL-4, IL-6 and IL-10.9 Rituximab may also affect autoreactive T cells and the production of T cell-modulating cytokines, autoantigen processing and the presentation of B cells.9 Rituximab may exhibit a dual effect in PV by depleting CD20 autoreactive B cells as progenitors of autoantibody secreting plasma cells and indirectly by decreasing the frequency of autoreactive CD4 T cells via depletion of B cells.10 It was hypothesized that regulatory B cells observed postrituximab could be responsible for the downregulation of Dsg-specific CD4 T cells through the secretion of IL-10.10 We report two cases of erosive LP successfully treated with the RA rituximab protocol. Conversely, cases of rituximabinduced LP are reported.5 Further investigation in prospective clinical trials is warranted. 1
Department of Dermatology, South Infirmary-Victoria University Hospital, Cork, Ireland 2 Cork University Dental School and Hospital, Wilton, Cork, Ireland E-mail: [email protected]
K. HEELAN1 M.A. MCALEER1 L. ROCHE1 C. MCCREARY2 M. MURPHY1
References 1 Parmentier L, Bron BA, Prins C et al. Mucocutaneous lichen planus with esophageal involvement: successful treatment with an anti-CD20 monoclonal antibody. Arch Dermatol 2008; 144:1427– 30. 2 Lavanya N, Jayanthi P, Rao UK, Ranganathan K. Oral lichen planus: an update on pathogenesis and treatment. J Oral Maxillofac Pathol 2011; 15:127–32. 3 O’Neill ID, Scully C. Biologics in oral medicine: ulcerative disorders. Oral Dis 2013; 19:37–45. British Journal of Dermatology (2015) 172, pp537–547
4 Gurcan HM, Keskin DB, Stern JN et al. A review of the current use of rituximab in autoimmune diseases. Int Immunopharmacol 2009; 9:10–25. 5 Heelan K, Al-Mohammedi F, Smith MJ et al. Durable remission of pemphigus with a fixed-dose rituximab protocol. JAMA Dermatol 2014; 150:703–8. 6 Heelan K, Walsh S, Shear NH. Treatment of mucous membrane pemphigoid with rituximab. J Am Acad Dermatol 2013; 69:310– 11. 7 Gregoriou S, Koutsoukou XA, Panayotides I et al. Pemphigus vulgaris of the epiglottis successfully treated with rituximab. J Eur Acad Dermatol Venereol 2014; DOI: 10.1111/jdv.12536. 8 Melet J, Mulleman D, Goupille P et al. Rituximab-induced T cell depletion in patients with rheumatoid arthritis: association with clinical response. Arthritis Rheum 2013; 65:2783–90. 9 Schmidt E, Hunzelmann N, Zillikens D et al. Rituximab in refractory autoimmune bullous diseases. Clin Exp Dermatol 2006; 31:503–8. 10 Colliou N, Picard D, Caillot F et al. Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response. Sci Transl Med 2013; 5: 175ra30. Funding sources: none. Conflicts of interest: none declared.
Human papillomavirus evaluation of vemurafenib-induced skin epithelial tumors: a case series DOI: 10.1111/bjd.13275 DEAR EDITOR, Vemurafenib, a kinase inhibitor, has been recently developed as a targeted therapy for patients with metastatic melanoma harbouring BRAF V600 mutations. A frequent sideeffect of treatment with BRAF inhibitors is the development of squamoproliferative epithelial neoplasms (reported in 41–60% of patients),1,2 termed by other authors as ‘BRAF inhibitorassociated verrucous keratosis’ (BAVK). BAVK lesions occur in an eruptive way and may clinically resemble common warts, keratoacanthomas or squamous cell carcinomas (SCCs). The exact mechanism of the development of BAVK has yet to be established; however, the occurrence of RAS mutations has been detected in 20–60% of patients.3,4 Recently, a few studies have investigated the other cofactors that may play a role in the pathogenesis of BAVKs, such as human papillomavirus (HPV) genotypes.5,6 HPVs are a large group of viruses with 174 completely characterized types. HPVs may infect epithelial cells in genital mucosa (a-HPVs), oral mucosa and skin (genotypes of all five genera: a-, b-, c-, l- and g-HPVs). In 2009, a working group of the International Agency for Research on Cancer classified 12 mucosal types of HPV (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) as carcinogenic to humans because of their association with cervical cancer (hereafter referred to as high-risk HPV types).7 These © 2014 British Association of Dermatologists
This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material.
Before therapy 100·00
**
After therapy
*
**
**
Score
80·00
Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan E-mail: [email protected]
60·00 40·00
References
20·00
ng
ns ct io
ni
m ot io
-F un
-E
x1 6
x1 6 Sk in
de
de Sk in
Sk in
de
x1 6
-S
de
x1 6
ym pt om s
-T ot al
0·00
Sk in
A. FUKUNAGA M. HATAKEYAMA M. TSUJIMOTO Y. ODA K. WASHIO C. NISHIGORI
Fig 1. Mean Skindex-16 subscale scores before and after steroid pulse therapy (*P < 0001, **P < 00001).
The mean total, symptoms, emotions and functioning scores before therapy were 705 88, 571 155, 792 72 and 690 72, respectively. Notably, the mean total and functioning scores before therapy in patients with AIGA were higher than those for other skin diseases including severe atopic dermatitis (total 606, functioning 412),6 severe psoriasis (total 537, functioning 405)7 and nonmelanoma skin cancer (functioning 121–151).5 All of the scores significantly improved after steroid pulse therapy (Fig. 1). In contrast, the total score for the patient who did not receive steroid pulse therapy (patient 2) was not significantly improved (change from 845 to 770) in the 6 months of follow-up. Similarly to previous reports, our study revealed that only two of eight patients with AIGA had sweat allergy detected by histamine release test on sweat or skin test using autologous sweat, suggesting that sweat allergy is not involved in the pathogenesis of AIGA.8,9 Steroid pulse therapy can generally improve the symptoms of AIGA.1,10 Only a few reports have documented the efficacy of pulse therapy. This report revealed that steroid pulse therapy alleviated the anhidrosis of all eight patients with AIGA, and adverse effects were not observed during follow-up. Symptomatic improvement was not observed in the patient who did not receive steroid pulse therapy. Moreover, symptomatic improvement was clearly linked to improved QoL. Notably, untreated AIGA was associated with considerably reduced QoL; the impact of AIGA on QoL was greater than that of other skin diseases. These observations suggest that steroid pulse therapy should be recommended as a standard therapy for patients with AIGA. This is the first report examining QoL in AIGA. Consideration of QoL in patients with AIGA is important in the assessment of suitable treatment. British Journal of Dermatology (2015) 172, pp537–547
1 Fukunaga A, Horikawa T, Sato M, Nishigori C. Acquired idiopathic generalized anhidrosis: possible pathogenic role of mast cells. Br J Dermatol 2009; 160:1337–40. 2 Kozaru T, Fukunaga A, Taguchi K et al. Rapid desensitization with autologous sweat in cholinergic urticaria. Allergol Int 2011; 60:277–81. 3 Fukunaga A, Bito T, Tsuru K et al. Responsiveness to autologous sweat and serum in cholinergic urticaria classifies its clinical subtypes. J Allergy Clin Immunol 2005; 116:397–402. 4 Higaki Y, Kawamoto K, Kamo T et al. The Japanese version of Skindex-16: a brief quality-of-life measure for patients with skin diseases. J Dermatol 2002; 29:693–8. 5 Chren MM, Sahay AP, Bertenthal DS et al. Quality-of-life outcomes of treatments for cutaneous basal cell carcinoma and squamous cell carcinoma. J Invest Dermatol 2007; 127:1351–7. 6 Kawashima M, Harada S. Effect of standard medication on quality of life of patients with atopic dermatitis. J Dermatol 2007; 34:9–16. 7 Okubo Y, Natsume S, Usui K et al. Low-dose, short-term ciclosporin (Neoralâ) therapy is effective in improving patients’ quality of life as assessed by Skindex-16 and GHQ-28 in mild to severe psoriasis patients. J Dermatol 2011; 38:465–72. 8 Nakamizo S, Egawa G, Miyachi Y, Kabashima K. Cholinergic urticaria: pathogenesis-based categorization and its treatment options. J Eur Acad Dermatol Venereol 2012; 26:114–16. 9 Sawada Y, Nakamura M, Bito T et al. Decreased expression of acetylcholine esterase in cholinergic urticaria with hypohidrosis or anhidrosis. J Invest Dermatol 2014; 134:276–9. 10 Ohshima Y, Yanagishita T, Ito K et al. Treatment of patients with acquired idiopathic generalized anhidrosis. Br J Dermatol 2013; 168:430–2. Funding sources: none. Conflicts of interest: none declared.
Intractable erosive lichen planus treated successfully with rituximab DOI: 10.1111/bjd.13537 DEAR EDITOR, Erosive lichen planus (LP) is a chronic recurrent disease manifesting as erosive ulcers affecting oral and genital mucosa.1,2 It can also affect oesophageal, lacrimal, conjunctival and laryngeal mucosa. High-potency topical corticosteroids are the first-line treatment; however, monotherapy is rarely successful. Alternatives include systemic corticosteroids, immunosuppressants and retinoids; however, the side-effects carry a significant morbidity. © 2014 British Association of Dermatologists
Correspondence 539
In recalcitrant cases, biological agents, including etanercept, adalimumab, infliximab, efalizumab, basiliximab and alefacept, have been used with some success.3 Parmentier et al. reported a case of mucocutaneous LP successfully treated with four intravenous courses (375 mg m 2) of rituximab at weekly intervals (lymphoma protocol).1 We report two cases of vulvovaginal gingival LP achieving remission with rituximab. The first case is that of a 46-year-old woman with a 6-month history of oral and vulvovaginal symptoms, including severe erosive vulvovaginitis and gingivitis. The diagnosis was confirmed by histopathology (Fig. 1). Aural symptoms comprised thickened inflamed tympanic membrane and auditory canal. Ophthalmological manifestations incorporated epiphoria and inflamed, stenosed lacrimal ducts. Past history included joint sarcoidosis. Initial treatment with topical superpotent steroid and tacrolimus yielded only a partial response. Courses of oral prednisolone did not achieve symptom control. Despite treatment with mycophenolate mofetil, symptoms persisted. Severe dysphagia restricted oral intake. Infliximab was commenced, producing a prompt response. Adalimumab was initiated as maintenance therapy. Remission lasted 18 months and prednisolone was tapered to 75 mg. Vaginal dilatation under anaesthesia was performed. Relapse of severe dysphagia and vulvovaginal symptoms occurred (Fig. 2a). Prednisolone 20 mg was started, adalimumab discontinued and infliximab restarted, but, on this occasion, it proved ineffective. Rituximab (1 g) on days 1 and 15 was commenced. Remission was achieved within 4 weeks of completion of infusion. Prednisolone was tapered by 5 mg weekly to a maintenance dose of 5 mg. Remission lasted 8 months (Fig. 2b). Relapse necessitated a course of prednisolone (20 mg), which was tapered by 5 mg every month to a maintenance dose of 5 mg. Relapses were treated with repeat infusions. Three infusions of 1 g each at approximately 5-
month intervals were given. Unfortunately, 14 months after the commencement of rituximab, breast carcinoma with spinal metastasis was diagnosed, and further rituximab was contraindicated. Current control is with short courses of oral prednisolone, topical clobetasol and interval vaginal and oesphageal dilatation. The second case is that of a 40-year-old woman with a 3-year history of oral LP. Initial treatment by an oral medicine physician included intralesional triamcinolone and steroid mouthwashes. Vulvovaginal symptoms and cutaneous involvement at the scalp and lower limbs developed. Dermatological opinion was sought, and histopathology from the vulva and foot confirmed LP. In this case, the disease was initially responsive to topical clobetasol but became recalcitrant. Colposcopy and vaginal dilatation were performed. Oral steroids were discontinued secondary to severe insomnia, hallucinations and mood swings. Mycophenolate mofetil was commenced but drug hypersensitivity developed. Rituximab (1 g) on days 1 and 15 was commenced. Remission was achieved within 4 weeks of treatment. A prophylactic dose of 1 g was given 5 months later. At the last follow-up, complete remission was maintained 8 months after the last infusion. Rituximab is chimeric murine–human monoclonal CD20 antibody approved for rheumatoid arthritis (RA), B-cell lymphomas and vasculitis.4 The mechanism of action includes antibody-dependent cytotoxicity, complement-mediated lysis,
(a)
(b)
Fig 1. Skin biopsy from vulva. Haematoxylin and eosin staining showing typical features of erosive lichen planus, including thinned epidermis with subepidermal hyalinization and deeper inflammatory infiltrate. © 2014 British Association of Dermatologists
Fig 2. (a) Severe erosive gingivitis of lower gingiva. (b) Normalappearing gingiva exhibiting remission of gingivitis. British Journal of Dermatology (2015) 172, pp537–547
540 Correspondence
direct disruption of signalling pathways and triggering of apoptosis.4 Off-label uses include pemphigus vulgaris (PV), mucosal membrane pemphigoid,5,6 paraneoplastic pemphigus and chronic graft-versus-host disease.4 Mucosal membrane diseases can be devastatingly destructive and in some cases fatal.5,6 PV of the epiglottis treated with rituximab was recently reported.7 The mechanism by which rituximab improves T cell-mediated LP is difficult to explain as it suggests B cells are implicated in the pathogenesis of LP. The majority of intraepithelial lymphocytes in oral LP are CD8+ cytotoxic T cells, but most lymphocytes in the lamina propria are CD4+ helper T (Th) cells. CD8+ cytotoxic T cells may be activated by the combination of antigen associated with major histocompatibility complex class I on basal keratinocytes and Th1 CD4+ T cellderived interleukin (IL)-2 and interferon-c.1,2 In RA, Melet et al. found rituximab caused a durable, reversible depletion of peripheral CD4+ and CD8+ T cells.8 Rituximab efficacy in PV is probably due to B-cell depletion resulting in decreased desmoglein (Dsg)-specific autoantibodies. PV pathogenesis likely involves both autoreactive Th1 and Th2 cells to promote autoantibody secretion by Dsg3-reactive B cells.9 Dsg3-specific T cells have also been demonstrated to release IL-4, IL-6 and IL-10.9 Rituximab may also affect autoreactive T cells and the production of T cell-modulating cytokines, autoantigen processing and the presentation of B cells.9 Rituximab may exhibit a dual effect in PV by depleting CD20 autoreactive B cells as progenitors of autoantibody secreting plasma cells and indirectly by decreasing the frequency of autoreactive CD4 T cells via depletion of B cells.10 It was hypothesized that regulatory B cells observed postrituximab could be responsible for the downregulation of Dsg-specific CD4 T cells through the secretion of IL-10.10 We report two cases of erosive LP successfully treated with the RA rituximab protocol. Conversely, cases of rituximabinduced LP are reported.5 Further investigation in prospective clinical trials is warranted. 1
Department of Dermatology, South Infirmary-Victoria University Hospital, Cork, Ireland 2 Cork University Dental School and Hospital, Wilton, Cork, Ireland E-mail: [email protected]
K. HEELAN1 M.A. MCALEER1 L. ROCHE1 C. MCCREARY2 M. MURPHY1
References 1 Parmentier L, Bron BA, Prins C et al. Mucocutaneous lichen planus with esophageal involvement: successful treatment with an anti-CD20 monoclonal antibody. Arch Dermatol 2008; 144:1427– 30. 2 Lavanya N, Jayanthi P, Rao UK, Ranganathan K. Oral lichen planus: an update on pathogenesis and treatment. J Oral Maxillofac Pathol 2011; 15:127–32. 3 O’Neill ID, Scully C. Biologics in oral medicine: ulcerative disorders. Oral Dis 2013; 19:37–45. British Journal of Dermatology (2015) 172, pp537–547
4 Gurcan HM, Keskin DB, Stern JN et al. A review of the current use of rituximab in autoimmune diseases. Int Immunopharmacol 2009; 9:10–25. 5 Heelan K, Al-Mohammedi F, Smith MJ et al. Durable remission of pemphigus with a fixed-dose rituximab protocol. JAMA Dermatol 2014; 150:703–8. 6 Heelan K, Walsh S, Shear NH. Treatment of mucous membrane pemphigoid with rituximab. J Am Acad Dermatol 2013; 69:310– 11. 7 Gregoriou S, Koutsoukou XA, Panayotides I et al. Pemphigus vulgaris of the epiglottis successfully treated with rituximab. J Eur Acad Dermatol Venereol 2014; DOI: 10.1111/jdv.12536. 8 Melet J, Mulleman D, Goupille P et al. Rituximab-induced T cell depletion in patients with rheumatoid arthritis: association with clinical response. Arthritis Rheum 2013; 65:2783–90. 9 Schmidt E, Hunzelmann N, Zillikens D et al. Rituximab in refractory autoimmune bullous diseases. Clin Exp Dermatol 2006; 31:503–8. 10 Colliou N, Picard D, Caillot F et al. Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response. Sci Transl Med 2013; 5: 175ra30. Funding sources: none. Conflicts of interest: none declared.
Human papillomavirus evaluation of vemurafenib-induced skin epithelial tumors: a case series DOI: 10.1111/bjd.13275 DEAR EDITOR, Vemurafenib, a kinase inhibitor, has been recently developed as a targeted therapy for patients with metastatic melanoma harbouring BRAF V600 mutations. A frequent sideeffect of treatment with BRAF inhibitors is the development of squamoproliferative epithelial neoplasms (reported in 41–60% of patients),1,2 termed by other authors as ‘BRAF inhibitorassociated verrucous keratosis’ (BAVK). BAVK lesions occur in an eruptive way and may clinically resemble common warts, keratoacanthomas or squamous cell carcinomas (SCCs). The exact mechanism of the development of BAVK has yet to be established; however, the occurrence of RAS mutations has been detected in 20–60% of patients.3,4 Recently, a few studies have investigated the other cofactors that may play a role in the pathogenesis of BAVKs, such as human papillomavirus (HPV) genotypes.5,6 HPVs are a large group of viruses with 174 completely characterized types. HPVs may infect epithelial cells in genital mucosa (a-HPVs), oral mucosa and skin (genotypes of all five genera: a-, b-, c-, l- and g-HPVs). In 2009, a working group of the International Agency for Research on Cancer classified 12 mucosal types of HPV (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) as carcinogenic to humans because of their association with cervical cancer (hereafter referred to as high-risk HPV types).7 These © 2014 British Association of Dermatologists
This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material.
