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Acute transverse myelitis during treatment with etanercept for severe plaque psoriasis
JAAD ONLINE CASE
LETTERS
Acute transverse myelitis during treatment with etanercept for severe plaque psoriasis To the Editor: Tumor necrosis factor alpha (TNF- ) inhibitors constitute a class of biologic treatments used in the management of psoriasis. Although these biologics have favored significant clinical improvement, there have been concerns for emerging side effects.1 We present a case of a patient with no prior history of demyelinating disease, who developed acute transverse myelitis (ATM) while being treated for chronic plaque psoriasis and psoriatic arthritis with etanercept. A 40-year-old woman with a 12-year history of psoriasis, treated with etanercept (50 mg weekly) for 21 months, presented with a 5-day history of paresthesias and muscular weakness that began over the lower extremities and gradually extended to the abdomen. The patient did not complain of any imbalance, gait disturbance, urinary or bowel incontinence, or any change in mental status. Neurologic examination revealed segmental sensory dysfunction with bilateral loss of pain and vibration sensation at levels C8-D1. The rest of the examination was unremarkable. Cerebrospinal fluid examination and laboratory results indicative of infectious or autoimmune cause were negative. Cranial magnetic resonance imaging (MRI) and visual evoked potentials were normal. MRI of the spinal cord revealed a hyperintense lesion at the third cervical (C3) level on T2-weighted images with intense contrast enhancement after gadolinium injection (Fig 1, A). Diagnosis of ATM was rendered. Etanercept was immediately discontinued and the patient was given intravenous methylprednisolone 1000 mg/day for 5 days in hospital. She was discharged with a short taper of prednisone, and clinical and imaging evaluation at 6 months showed complete resolution of ATM (Fig 1, B). The patient was started on ustekinumab, a human interleukin 12/23 monoclonal antibody. Treatment was successful with clearing of erythematous squamous lesions and no recurrence of neurologic symptoms or demyelination. TNF- drugs have been used for the treatment of rheumatoid arthritis, psoriatic arthritis, psoriasis, ankylosing spondylitis, juvenile chronic arthritis, and Crohn’s disease. Several studies have raised the possibility that TNF- inhibitors may be associated with neurologic adverse events including central and peripheral nervous system demyelination.2 In 2006, J AM ACAD DERMATOL
Fig 1. A, Magnetic resonance imaging (MRI) study showing hyperintense lesion at C3 level on T2-weighted images with intense contrast enhancement after gadolinium injection. B, MRI scan of cervical spinal cord 6 months later. The demyelinating lesion has disappeared totally.
Sukal et al reported a case of demyelinating disease in a patient with psoriasis treated with etanercept.3 Recently, Mahil et al published a review summarizing clinical data extracted on 65 reported cases of central nervous system demyelination in patients receiving TNF- inhibitors.4 Ustekinumab is a fully human monoclonal antibody against IL12/23 p40 approved for the treatment of moderate to severe plaque psoriasis. Targeting IL12/23 pathway has been examined for multiple sclerosis treatment in a phase 2 study.5 In our case, there was no clinical or laboratory finding indicative of any disease as the cause of ATM and given the temporal relationship, we JANUARY 2014 e17
J AM ACAD DERMATOL
e18 Letters
JANUARY 2014
considered the possibility of an adverse effect to etanercept. During follow-up, clinical indicators and MRI findings showed amelioration upon cessation of treatment. At present, the patient remains under treatment with ustekinumab at regular doses and maintains good clinical response without development of severe adverse effects. Given the uncertainty in this area, it seems reasonable to avoid the use of anti-TNF- agents and offer an alternative regimen in patients with a personal or family history of demyelinating disease. Juan Escalas, PhD, MD,a Nicole Kn€ opfel, MD,a a Ana Martin-Santiago, MD, and Carmen Calles, MDb Departments of Dermatologya and Neurology,b Hospital Universitari Son Espases, Palma Mallorca, Spain Funding sources: None.
Fig 1. Cutaneous intestinal metaplasia. Hematoxylin and eosin (top). CK20 immunohistochemistry (bottom).
Conflicts of interest: None declared. Correspondence to: Juan Escalas, PhD, MD, Dermatology Department, Hospital Universitari Son Espases, Ctra de Valldemossa, 79, 07010 Palma Mallorca, Spain E-mail: [email protected] REFERENCES 1. Rustin MH. Long-term safety of biologics in the treatment of moderate-to-severe plaque psoriasis: review of current data. Br J Dermatol 2012;167(suppl 3):3-11. 2. Scheinfeld N. A comprehensive review and evaluation of the side effects of the tumor necrosis factor alpha blockers etanercept, infliximab and adalimumab. J Dermatolog Treat 2004;15:280-94. 3. Sukal SA, Nadiminti L, Granstein RD. Etanercept and demyelinating disease in a patient with psoriasis. J Am Acad Dermatol 2006;54:160-4. 4. Mahil SK, Andrews TC, Brierley C, Barker JN, Smith CH. Demyelination during tumour necrosis factor antagonist therapy for psoriasis: a case report and review of the literature. J Dermatolog Treat 2013;24:38-49. 5. Segal BM, Constantinescu CS, Raychaudhuri A, Kim L, Fidelus-Gort R, Kasper LH, et al. Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomized, dose-ranging study. Lancet Neurol 2008;7:796-804. http://dx.doi.org/10.1016/j.jaad.2013.08.047
Ostomy associated cutaneous colonic metaplasia To the Editor: More than 70% of people with surgically induced intestinal stomas experience peristomal skin complications, including contact reactions, malignant neoplasms, preexisting skin diseases,
infections, pyoderma gangrenosum, and other ulcerations.1 However, to our knowledge, there has been only 1 reported case in the literature describing a peristomal skin ulcer with scattered intestinal tubular glands consistent with cutaneous intestinal metaplasia,2 which is distinct from lesions of overgranulation with intestinal metaplasia.1-3 We describe the second case of cutaneous peristomal intestinal metaplasia. A 76-year-old Caucasian female with history of ulcerative colitis, who had undergone a colectomy at age 17 resulting in a right lower abdominal ileostomy, presented to the dermatology department with a 2-year history of persistent stinging and irritation at the ileostomy site. She denied any changes in her stoma care. Her ulcerative colitis had been well controlled since the surgery. On physical exam there was a red, superficially erosive plaque extending along the cutaneous border of the stoma, initially suggestive of irritant dermatitis. Topical triamcinolone 0.1% ointment every other day for 1 month was recommended at that time, without improvement of the erosion or symptoms on follow-up. Zinc oxide ointment mixed with triamcinolone ointment was recommended for an additional 3 months, but lack of significant improvement on follow-up prompted a punch biopsy of the plaque. Histologic examination showed alternating epidermis with granular layer and colonic-type glandular mucosa, numerous goblet cells, and no discernible Paneth cells (Fig 1). The glandular elements expressed epithelial mucin, and by immunohistochemistry showed strong, diffuse expression
LETTERS
Acute transverse myelitis during treatment with etanercept for severe plaque psoriasis To the Editor: Tumor necrosis factor alpha (TNF- ) inhibitors constitute a class of biologic treatments used in the management of psoriasis. Although these biologics have favored significant clinical improvement, there have been concerns for emerging side effects.1 We present a case of a patient with no prior history of demyelinating disease, who developed acute transverse myelitis (ATM) while being treated for chronic plaque psoriasis and psoriatic arthritis with etanercept. A 40-year-old woman with a 12-year history of psoriasis, treated with etanercept (50 mg weekly) for 21 months, presented with a 5-day history of paresthesias and muscular weakness that began over the lower extremities and gradually extended to the abdomen. The patient did not complain of any imbalance, gait disturbance, urinary or bowel incontinence, or any change in mental status. Neurologic examination revealed segmental sensory dysfunction with bilateral loss of pain and vibration sensation at levels C8-D1. The rest of the examination was unremarkable. Cerebrospinal fluid examination and laboratory results indicative of infectious or autoimmune cause were negative. Cranial magnetic resonance imaging (MRI) and visual evoked potentials were normal. MRI of the spinal cord revealed a hyperintense lesion at the third cervical (C3) level on T2-weighted images with intense contrast enhancement after gadolinium injection (Fig 1, A). Diagnosis of ATM was rendered. Etanercept was immediately discontinued and the patient was given intravenous methylprednisolone 1000 mg/day for 5 days in hospital. She was discharged with a short taper of prednisone, and clinical and imaging evaluation at 6 months showed complete resolution of ATM (Fig 1, B). The patient was started on ustekinumab, a human interleukin 12/23 monoclonal antibody. Treatment was successful with clearing of erythematous squamous lesions and no recurrence of neurologic symptoms or demyelination. TNF- drugs have been used for the treatment of rheumatoid arthritis, psoriatic arthritis, psoriasis, ankylosing spondylitis, juvenile chronic arthritis, and Crohn’s disease. Several studies have raised the possibility that TNF- inhibitors may be associated with neurologic adverse events including central and peripheral nervous system demyelination.2 In 2006, J AM ACAD DERMATOL
Fig 1. A, Magnetic resonance imaging (MRI) study showing hyperintense lesion at C3 level on T2-weighted images with intense contrast enhancement after gadolinium injection. B, MRI scan of cervical spinal cord 6 months later. The demyelinating lesion has disappeared totally.
Sukal et al reported a case of demyelinating disease in a patient with psoriasis treated with etanercept.3 Recently, Mahil et al published a review summarizing clinical data extracted on 65 reported cases of central nervous system demyelination in patients receiving TNF- inhibitors.4 Ustekinumab is a fully human monoclonal antibody against IL12/23 p40 approved for the treatment of moderate to severe plaque psoriasis. Targeting IL12/23 pathway has been examined for multiple sclerosis treatment in a phase 2 study.5 In our case, there was no clinical or laboratory finding indicative of any disease as the cause of ATM and given the temporal relationship, we JANUARY 2014 e17
J AM ACAD DERMATOL
e18 Letters
JANUARY 2014
considered the possibility of an adverse effect to etanercept. During follow-up, clinical indicators and MRI findings showed amelioration upon cessation of treatment. At present, the patient remains under treatment with ustekinumab at regular doses and maintains good clinical response without development of severe adverse effects. Given the uncertainty in this area, it seems reasonable to avoid the use of anti-TNF- agents and offer an alternative regimen in patients with a personal or family history of demyelinating disease. Juan Escalas, PhD, MD,a Nicole Kn€ opfel, MD,a a Ana Martin-Santiago, MD, and Carmen Calles, MDb Departments of Dermatologya and Neurology,b Hospital Universitari Son Espases, Palma Mallorca, Spain Funding sources: None.
Fig 1. Cutaneous intestinal metaplasia. Hematoxylin and eosin (top). CK20 immunohistochemistry (bottom).
Conflicts of interest: None declared. Correspondence to: Juan Escalas, PhD, MD, Dermatology Department, Hospital Universitari Son Espases, Ctra de Valldemossa, 79, 07010 Palma Mallorca, Spain E-mail: [email protected] REFERENCES 1. Rustin MH. Long-term safety of biologics in the treatment of moderate-to-severe plaque psoriasis: review of current data. Br J Dermatol 2012;167(suppl 3):3-11. 2. Scheinfeld N. A comprehensive review and evaluation of the side effects of the tumor necrosis factor alpha blockers etanercept, infliximab and adalimumab. J Dermatolog Treat 2004;15:280-94. 3. Sukal SA, Nadiminti L, Granstein RD. Etanercept and demyelinating disease in a patient with psoriasis. J Am Acad Dermatol 2006;54:160-4. 4. Mahil SK, Andrews TC, Brierley C, Barker JN, Smith CH. Demyelination during tumour necrosis factor antagonist therapy for psoriasis: a case report and review of the literature. J Dermatolog Treat 2013;24:38-49. 5. Segal BM, Constantinescu CS, Raychaudhuri A, Kim L, Fidelus-Gort R, Kasper LH, et al. Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomized, dose-ranging study. Lancet Neurol 2008;7:796-804. http://dx.doi.org/10.1016/j.jaad.2013.08.047
Ostomy associated cutaneous colonic metaplasia To the Editor: More than 70% of people with surgically induced intestinal stomas experience peristomal skin complications, including contact reactions, malignant neoplasms, preexisting skin diseases,
infections, pyoderma gangrenosum, and other ulcerations.1 However, to our knowledge, there has been only 1 reported case in the literature describing a peristomal skin ulcer with scattered intestinal tubular glands consistent with cutaneous intestinal metaplasia,2 which is distinct from lesions of overgranulation with intestinal metaplasia.1-3 We describe the second case of cutaneous peristomal intestinal metaplasia. A 76-year-old Caucasian female with history of ulcerative colitis, who had undergone a colectomy at age 17 resulting in a right lower abdominal ileostomy, presented to the dermatology department with a 2-year history of persistent stinging and irritation at the ileostomy site. She denied any changes in her stoma care. Her ulcerative colitis had been well controlled since the surgery. On physical exam there was a red, superficially erosive plaque extending along the cutaneous border of the stoma, initially suggestive of irritant dermatitis. Topical triamcinolone 0.1% ointment every other day for 1 month was recommended at that time, without improvement of the erosion or symptoms on follow-up. Zinc oxide ointment mixed with triamcinolone ointment was recommended for an additional 3 months, but lack of significant improvement on follow-up prompted a punch biopsy of the plaque. Histologic examination showed alternating epidermis with granular layer and colonic-type glandular mucosa, numerous goblet cells, and no discernible Paneth cells (Fig 1). The glandular elements expressed epithelial mucin, and by immunohistochemistry showed strong, diffuse expression