Correspondence 987 Table 2 Outcomes after treatment with infliximab (n = 11) Outcome Duration of therapy (months), median 491 (18–87) (range) Duration of patient follow-up (months), 603 (18–87) median (range) Number of patients remaining on 9 treatment Reason for cessation of therapy: 2/2 secondary failure DLQI current score (change) 128 ( 153) VAS for pain current 34 ( 41) score (change) Adverse events Weight gain (kg) 22 Infection requiring antibiotics (culture proven) Cutaneous 9 episodes in 4 patients Respiratory tract 4 episodes in 3 patients Tonsillitis 1 episode in 1 patient Malignancy Hodgkin lymphoma 1 patient, 36 months after cessation of infliximab The median value is used in view of the small dataset. VAS, visual analogue scale; DLQI, Dermatology Life Quality Index.
603 months. All patients experienced initial disease improvement as assessed by the VAS, DLQI and physician’s clinical assessment. Two patients who experienced secondary failure at 12 months and 19 months, respectively, were switched to an alternative agent. The median DLQI score decreased by 153 points to 128 (range 1–24). The median VAS score for pain decreased by 41 points to 34 (range 1–8). Despite prescription of topical chlorhexidine wash for thrice-weekly use, four patients required nine courses of antibiotics for culture-proven secondary infections of HS lesions [b-haemolytic Streptococcus group B (3), b-haemolytic Streptococcus group F (1), Proteus mirabilis (3), Staphylococcus aureus (2)]. Three patients developed five other culture-proven infections [respiratory tract infections (4), tonsillitis (1)], which were treated with oral antibiotics and necessitated cancellation of at least one infliximab infusion. One patient was diagnosed with Hodgkin lymphoma 36 months after switching from infliximab to adalimumab. He is currently responding well to chemotherapy. Patients experienced a median weight gain of 22 kg (range–32 to 81 kg). No patient has been admitted to hospital for management of infection. No patient has developed tuberculosis. No cardiovascular events, demyelination or liver dysfunction have been diagnosed in our cohort. We describe 11 patients with severe HS unresponsive to more than three prior therapies who received infliximab 5 mg kg 1 every 4 weeks with a median follow-up of 603 months. Nine of the 11 patients remain well controlled on this regimen. While on this regimen our patients experienced secondary infections of HS lesions, respiratory tract infections, tonsillitis and minor weight gain. One patient © 2013 British Association of Dermatologists
developed Hodgkin lymphoma 3 years after switching to adalimumab. The risk of Hodgkin lymphoma is not thought to be associated with the use of anti-TNF-a antagonists, although other subtypes of lymphoma are found to occur more frequently.7,8 We suggest that the optimal dosing schedule for the use of infliximab in the treatment of HS is yet to be determined and that dermatologists should consider using dosing schedules for inflammatory joint and bowel disease in the management of patients severely affected with HS. Department of Dermatology, King’s College Hospital, Denmark Hill, London SE5 9RS, U.K. E-mail: [email protected]
B. MORIARTY Z. JIYAD D. CREAMER
References 1 Rosner IA, Richter DE, Huettner TL et al. Spondyloarthropathy associated with hidradenitis suppurative and acne conglobata. Ann Intern Med 1982; 97:520–5. 2 Alzaga Fernandez AG, Demirci H, Darnley-Fisch DA, Steen DW. Interstitial keratitis secondary to severe hidradenitis suppurativa: a case report and literature review. Cornea 2010; 29:1189–91. 3 Wolkenstein P, Loundou A, Barrau K et al. Quality of life impairment in hidradenitis suppurativa: a study of 61 cases. J Am Acad Dermatol 2007; 56:621–3. 4 Grant A, Gonzalez T, Montgomery MO et al. Infliximab therapy for patients with moderate to severe hidradenitis suppurativa: a randomized, double-blind, placebo-controlled crossover trial. J Am Acad Dermatol 2010; 62:205–17. 5 Kimball AB, Kerdel F, Adams D et al. Adalimumab for the treatment of moderate to severe hidradenitis suppurativa: a parallel randomized trial. Ann Intern Med 2012; 157:846–55. 6 Smith CH, Anstey AV, Barker JN et al. British Association of Dermatologists’ guidelines for biologic interventions for psoriasis 2009. Br J Dermatol 2009; 161:987–1019. 7 Mariette X, Tubach F, Bagheri H et al. Lymphoma in patients treated with anti-TNF: results of the 3-year prospective French RATIO registry. Ann Rheum Dis 2010; 69:400–8. 8 Burmester GR, Panaccione R, Gordon KB et al. Adalimumab: longterm safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn’s disease. Ann Rheum Dis 2013; 72:517–24. Funding sources: none. Conflicts of interest: none declared.
Narrowband ultraviolet B phototherapy in erythropoietic protoporphyria: case series DOI: 10.1111/bjd.12714 DEAR EDITOR, Erythropoietic protoporphyria (EPP) is an inherited disorder of the haem metabolic pathway. It causes British Journal of Dermatology (2014) 170, pp970–1001
988 Correspondence
disabling cutaneous photosensitivity and, sometimes, liver disease due to the accumulation of protoporphyrin in blood, liver and other tissues.1 Holme et al. reported the median age at onset and diagnosis in patients with EPP in the U.K. as 1 and 12 years, respectively, with diagnosis being delayed until the age of 20 years or more in 34% of their patients.2 However, late presentation of EPP in adults has been reported.3 The mechanism of cutaneous photosensitivity is not entirely known. The primary event appears to be endothelial damage caused by the photodynamic reaction of the accumulating protoporphyrin. Mast cell and complement activation may also be responsible for the clinical manifestations in EPP.4 Behavioural measures, wearing protective clothing and opaque sun blocks are useful in preventing photosensitivity but often unacceptable in this young group of patients. A systematic review of treatment options in EPP did not detect an efficacy of b-carotene, vitamin C or N-acetyl cysteine in well-designed studies.5 Narrowband ultraviolet B phototherapy (NBUVB) is widely used as a prophylactic treatment for many photodermatoses, especially for polymorphic light eruption (PLE). A two- to fourfold increase in minimal erythema dose (MED) to relevant visible wavebands was demonstrated after NBUVB in five patients with EPP. Patients also reported a favourable response after treatment with NBUVB, with sunlight exposure tolerance increasing by up to 2 h.6 We would like to share our experience of NBUVB in the treatment of patients with EPP over the past 20 years. We did a retrospective analysis of case notes of all patients with EPP who received NBUVB. The regimen followed for NBUVB treatment was similar to that for PLE with a starting dose of 50–70% of MED and 20% increments, and then reduced to 10% increments, with usually up to 15 treatments. Twelve patients (nine female) were treated with a total of 80 annual courses of NBUVB phototherapy (Philips TL-01 lamp; Philips, Eindhoven, the Netherlands) between 1991 and 2011. The mean age of the patients was 28 years and the majority had skin phototype I. The mean age at onset of the disease was 24 years, except for one patient who had late onset of EPP at the age of 44 years. The mean duration to diagnosis from the onset of disease was 37 years. The diagnosis was established based on clinical history, signs, qualitative plasma porphyrin scan and quantitative erythrocyte porphyrins. Ten who were phototested had abnormal monochromator response to relevant visible wavebands. None of them had abnormal response to any UVB waveband. MED to NBUVB at 24 h was normal in all of the patients. The mean number of total treatments per course ranged from eight to 15 and the mean final dose per course was between 019 and 092 J cm 2. Seven patients reported good benefit, four patients reported no benefit and no information on efficacy was available for one patient. Two patients reported an increase in duration of tolerance to sunlight up to
British Journal of Dermatology (2014) 170, pp970–1001
15 h after NBUVB compared with a few minutes prior to treatment. Three patients commented on a better tolerance of sunlight abroad. Three patients commented on the duration of efficacy and felt that it lasted for 6–9 months. The treatment was well tolerated with well-demarcated erythema as a side-effect only in two patients. EPP-like symptoms occurred in two patients but was due to daylight exposure early in the course of treatment. Both were able to continue with treatment after a short interval. Two received their NBUVB phototherapy at home: one received three courses and the other had four courses. The number of treatments ranged from 15 to 20 per course. Both of them reported good benefit and tolerated the treatment well without any EPP-like symptoms. NBUVB phototherapy was beneficial and well tolerated in our group of patients with EPP. Home phototherapy was also found to be effective and well tolerated in our patients. The main mechanism of induced tolerance causing the therapeutic benefit could be due to physical photoadaptation. It is possible that effects of NBUVB on cutaneous immune function, such as effects on mast cells, could also contribute to the therapeutic benefit. An ideal study would be a randomized controlled trial, which due to the low prevalence of EPP would have to involve more than one centre. Home NBUVB phototherapy could be offered in such a study to allow recruitment of patients over a wide geographical area. Scottish Cutaneous Porphyria Service, Department of Dermatology and Photobiology, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. E-mail: [email protected]
M. SIVARAMAKRISHNAN J. WOODS R. DAWE
References 1 Lecha M, Puy H, Deybach J-C. Erythropoietic protoporphyria. Orphanet J Rare Dis 2009; 4:19. 2 Holme SA, Anstey AV, Finlay AY et al. Erythropoietic protoporphyria in the U.K.: clinical features and effect on quality of life. Br J Dermatol 2006; 155:574–81. 3 Berroeta L, Man I, Goudie DR et al. Late presentation of erythropoietic protoporphyria: case report and genetic analysis of family members. Br J Dermatol 2007; 157:1030–1. 4 Brun A, Sandberg S. Mechanisms of photosensitivity in porphyric patients with special emphasis on erythropoietic protoporphyria. J Photochem Photobiol B 1991; 10:285–302. 5 Minder EI, Schneider-Yin X, Steurer J, Bachmann LM. A systematic review of treatment options for dermal photosensitivity in erythropoietic protoporphyria. Cell Mol Biol 2009; 55:84–97. 6 Collins P, Ferguson J. Narrowband UVB (TL-01) phototherapy: an effective preventative treatment for the photodermatoses. Br J Dermatol 1995; 132:9560–63. Funding resources: none. Conflicts of interest: none declared.
© 2013 British Association of Dermatologists
603 months. All patients experienced initial disease improvement as assessed by the VAS, DLQI and physician’s clinical assessment. Two patients who experienced secondary failure at 12 months and 19 months, respectively, were switched to an alternative agent. The median DLQI score decreased by 153 points to 128 (range 1–24). The median VAS score for pain decreased by 41 points to 34 (range 1–8). Despite prescription of topical chlorhexidine wash for thrice-weekly use, four patients required nine courses of antibiotics for culture-proven secondary infections of HS lesions [b-haemolytic Streptococcus group B (3), b-haemolytic Streptococcus group F (1), Proteus mirabilis (3), Staphylococcus aureus (2)]. Three patients developed five other culture-proven infections [respiratory tract infections (4), tonsillitis (1)], which were treated with oral antibiotics and necessitated cancellation of at least one infliximab infusion. One patient was diagnosed with Hodgkin lymphoma 36 months after switching from infliximab to adalimumab. He is currently responding well to chemotherapy. Patients experienced a median weight gain of 22 kg (range–32 to 81 kg). No patient has been admitted to hospital for management of infection. No patient has developed tuberculosis. No cardiovascular events, demyelination or liver dysfunction have been diagnosed in our cohort. We describe 11 patients with severe HS unresponsive to more than three prior therapies who received infliximab 5 mg kg 1 every 4 weeks with a median follow-up of 603 months. Nine of the 11 patients remain well controlled on this regimen. While on this regimen our patients experienced secondary infections of HS lesions, respiratory tract infections, tonsillitis and minor weight gain. One patient © 2013 British Association of Dermatologists
developed Hodgkin lymphoma 3 years after switching to adalimumab. The risk of Hodgkin lymphoma is not thought to be associated with the use of anti-TNF-a antagonists, although other subtypes of lymphoma are found to occur more frequently.7,8 We suggest that the optimal dosing schedule for the use of infliximab in the treatment of HS is yet to be determined and that dermatologists should consider using dosing schedules for inflammatory joint and bowel disease in the management of patients severely affected with HS. Department of Dermatology, King’s College Hospital, Denmark Hill, London SE5 9RS, U.K. E-mail: [email protected]
B. MORIARTY Z. JIYAD D. CREAMER
References 1 Rosner IA, Richter DE, Huettner TL et al. Spondyloarthropathy associated with hidradenitis suppurative and acne conglobata. Ann Intern Med 1982; 97:520–5. 2 Alzaga Fernandez AG, Demirci H, Darnley-Fisch DA, Steen DW. Interstitial keratitis secondary to severe hidradenitis suppurativa: a case report and literature review. Cornea 2010; 29:1189–91. 3 Wolkenstein P, Loundou A, Barrau K et al. Quality of life impairment in hidradenitis suppurativa: a study of 61 cases. J Am Acad Dermatol 2007; 56:621–3. 4 Grant A, Gonzalez T, Montgomery MO et al. Infliximab therapy for patients with moderate to severe hidradenitis suppurativa: a randomized, double-blind, placebo-controlled crossover trial. J Am Acad Dermatol 2010; 62:205–17. 5 Kimball AB, Kerdel F, Adams D et al. Adalimumab for the treatment of moderate to severe hidradenitis suppurativa: a parallel randomized trial. Ann Intern Med 2012; 157:846–55. 6 Smith CH, Anstey AV, Barker JN et al. British Association of Dermatologists’ guidelines for biologic interventions for psoriasis 2009. Br J Dermatol 2009; 161:987–1019. 7 Mariette X, Tubach F, Bagheri H et al. Lymphoma in patients treated with anti-TNF: results of the 3-year prospective French RATIO registry. Ann Rheum Dis 2010; 69:400–8. 8 Burmester GR, Panaccione R, Gordon KB et al. Adalimumab: longterm safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn’s disease. Ann Rheum Dis 2013; 72:517–24. Funding sources: none. Conflicts of interest: none declared.
Narrowband ultraviolet B phototherapy in erythropoietic protoporphyria: case series DOI: 10.1111/bjd.12714 DEAR EDITOR, Erythropoietic protoporphyria (EPP) is an inherited disorder of the haem metabolic pathway. It causes British Journal of Dermatology (2014) 170, pp970–1001
988 Correspondence
disabling cutaneous photosensitivity and, sometimes, liver disease due to the accumulation of protoporphyrin in blood, liver and other tissues.1 Holme et al. reported the median age at onset and diagnosis in patients with EPP in the U.K. as 1 and 12 years, respectively, with diagnosis being delayed until the age of 20 years or more in 34% of their patients.2 However, late presentation of EPP in adults has been reported.3 The mechanism of cutaneous photosensitivity is not entirely known. The primary event appears to be endothelial damage caused by the photodynamic reaction of the accumulating protoporphyrin. Mast cell and complement activation may also be responsible for the clinical manifestations in EPP.4 Behavioural measures, wearing protective clothing and opaque sun blocks are useful in preventing photosensitivity but often unacceptable in this young group of patients. A systematic review of treatment options in EPP did not detect an efficacy of b-carotene, vitamin C or N-acetyl cysteine in well-designed studies.5 Narrowband ultraviolet B phototherapy (NBUVB) is widely used as a prophylactic treatment for many photodermatoses, especially for polymorphic light eruption (PLE). A two- to fourfold increase in minimal erythema dose (MED) to relevant visible wavebands was demonstrated after NBUVB in five patients with EPP. Patients also reported a favourable response after treatment with NBUVB, with sunlight exposure tolerance increasing by up to 2 h.6 We would like to share our experience of NBUVB in the treatment of patients with EPP over the past 20 years. We did a retrospective analysis of case notes of all patients with EPP who received NBUVB. The regimen followed for NBUVB treatment was similar to that for PLE with a starting dose of 50–70% of MED and 20% increments, and then reduced to 10% increments, with usually up to 15 treatments. Twelve patients (nine female) were treated with a total of 80 annual courses of NBUVB phototherapy (Philips TL-01 lamp; Philips, Eindhoven, the Netherlands) between 1991 and 2011. The mean age of the patients was 28 years and the majority had skin phototype I. The mean age at onset of the disease was 24 years, except for one patient who had late onset of EPP at the age of 44 years. The mean duration to diagnosis from the onset of disease was 37 years. The diagnosis was established based on clinical history, signs, qualitative plasma porphyrin scan and quantitative erythrocyte porphyrins. Ten who were phototested had abnormal monochromator response to relevant visible wavebands. None of them had abnormal response to any UVB waveband. MED to NBUVB at 24 h was normal in all of the patients. The mean number of total treatments per course ranged from eight to 15 and the mean final dose per course was between 019 and 092 J cm 2. Seven patients reported good benefit, four patients reported no benefit and no information on efficacy was available for one patient. Two patients reported an increase in duration of tolerance to sunlight up to
British Journal of Dermatology (2014) 170, pp970–1001
15 h after NBUVB compared with a few minutes prior to treatment. Three patients commented on a better tolerance of sunlight abroad. Three patients commented on the duration of efficacy and felt that it lasted for 6–9 months. The treatment was well tolerated with well-demarcated erythema as a side-effect only in two patients. EPP-like symptoms occurred in two patients but was due to daylight exposure early in the course of treatment. Both were able to continue with treatment after a short interval. Two received their NBUVB phototherapy at home: one received three courses and the other had four courses. The number of treatments ranged from 15 to 20 per course. Both of them reported good benefit and tolerated the treatment well without any EPP-like symptoms. NBUVB phototherapy was beneficial and well tolerated in our group of patients with EPP. Home phototherapy was also found to be effective and well tolerated in our patients. The main mechanism of induced tolerance causing the therapeutic benefit could be due to physical photoadaptation. It is possible that effects of NBUVB on cutaneous immune function, such as effects on mast cells, could also contribute to the therapeutic benefit. An ideal study would be a randomized controlled trial, which due to the low prevalence of EPP would have to involve more than one centre. Home NBUVB phototherapy could be offered in such a study to allow recruitment of patients over a wide geographical area. Scottish Cutaneous Porphyria Service, Department of Dermatology and Photobiology, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. E-mail: [email protected]
M. SIVARAMAKRISHNAN J. WOODS R. DAWE
References 1 Lecha M, Puy H, Deybach J-C. Erythropoietic protoporphyria. Orphanet J Rare Dis 2009; 4:19. 2 Holme SA, Anstey AV, Finlay AY et al. Erythropoietic protoporphyria in the U.K.: clinical features and effect on quality of life. Br J Dermatol 2006; 155:574–81. 3 Berroeta L, Man I, Goudie DR et al. Late presentation of erythropoietic protoporphyria: case report and genetic analysis of family members. Br J Dermatol 2007; 157:1030–1. 4 Brun A, Sandberg S. Mechanisms of photosensitivity in porphyric patients with special emphasis on erythropoietic protoporphyria. J Photochem Photobiol B 1991; 10:285–302. 5 Minder EI, Schneider-Yin X, Steurer J, Bachmann LM. A systematic review of treatment options for dermal photosensitivity in erythropoietic protoporphyria. Cell Mol Biol 2009; 55:84–97. 6 Collins P, Ferguson J. Narrowband UVB (TL-01) phototherapy: an effective preventative treatment for the photodermatoses. Br J Dermatol 1995; 132:9560–63. Funding resources: none. Conflicts of interest: none declared.
© 2013 British Association of Dermatologists
