Correspondence
References 1 Ximena E, del Puerto C, Mario P, et al. Ectopic extramammary Pagets disease on the face. Indian J Dermatol Venereol Leprol 2012; 78: 760–762. 2 Gal-Or N, Gil T, Amir A, et al. Management of invasive extramammary Pagets disease of the axilla—a case report. Eur J Plast Surg 2012; 35: 771–773. 3 Pierie JP, Choudry U, Muzikansky A, et al. Prognosis and management of extramammary Pagets disease and the association with secondary malignancies. J Am Coll Surg 2003; 196: 45–50. 4 Ito Y, Igawa S, Ohishi Y, et al. Prognostic indicators in 35 patients with extramammary Pagets disease. Dermatol Surg 2012; 38: 1938–1944. 5 Ohnishi T, Watanabe S. The use of cytokeratins 7 and 20 in the diagnosis of primary and secondary extramammary Pagets disease. Br J Dermatol 2000; 142: 243–247. 6 Dıaz de Le on E, Carcangiu ML, Prieto VG, et al. Extramammary Paget disease is characterized by the consistent lack of estrogen and progesterone receptors but frequently express androgen receptor. Am J Clin Pathol 2000; 113: 572–575. 7 Masuguchi S, Jinnin M, Fukushima S, et al. The expression of HER-2 in extramammary Pagets disease. BioSci Trends 2011; 5: 151–155. 8 Chang J, Prieto VG, Sangueza M, et al. Diagnostic utility of p63 expression in the differential diagnosis of pagetoid squamus cell carcinoma in situ and extramammary Paget disease: a histopathologic study of 70 cases. Am J Dermatopathol 2014; 36: 49–53. 9 Chanda JJ. Extramammary Pagets disease: prognosis and relationship to internal malignancy. J Am Acad Dermatol 1985; 13: 1009–1014. 10 McKee P. Cutaneous cyst. In: Mckee PH, Carlonje E, Brenn T, Lazar A, eds. McKee’s Pathology of the Skin, 4th edn. China: Elsevier Saunders, 2012: 1571.
A 77-year-old Japanese man was referred to our department because of a 1-month history of multiple painful skin ulcerations. He had UC controlled by salazosulfapyridine and, by the time he consulted for the skin lesions, had experienced no abdominal symptoms for at least one year. Physical examination revealed slightly painful ulcers with sharply marginated, undermined, erythematous borders on the thigh, back, nose, and scrotum (Fig. 1a). His left eye showed slight redness and a scleral ulcer (Fig. 1b). His white blood cell count and C-reactive protein were 9.2 9 103/ll and 10.79 mg/dl, respectively. Antinuclear and neutrophil cytoplasmic antibodies and rheumatoid factor were negative. A skin biopsy specimen showed dense, neutrophilic infiltration in the dermis and subcutaneous fat without granuloma or vasculitis (Fig. 2). Tissue cultures for bacteria, fungi, and mycobacteria were negative. Based on these findings, we made the diagnosis of PG. Ophthalmologists diagnosed anterior necrotizing scleritis upon ocular signs. Oral prednisone at 60 mg/day and topical clobetasol propionate treatment for the skin lesions were initiated, as was topical eye drop treatment with moxifloxacin hydrochloride, betamethasone sodium phosphate, and ofloxacin for the scleritis. The skin lesions
(a)
A case of pyoderma gangrenosum associated with anterior necrotizing scleritis in a patient with ulcerative colitis (b)
Pyoderma gangrenosum with scleritis Pyoderma gangrenosum (PG) is a chronic necrotizing inflammatory skin disease of unknown origin that presents in one of four clinical variants: ulcerative, pustular, bullous, and vegetative. More than 50% of PG cases, particularly the ulcerative PG variant, are associated with an underlying disease. Commonly associated conditions include inflammatory bowel disease (IBD) such as ulcerative colitis (UC) and Crohn’s disease, polyarthritis, hematologic diseases, and neoplasia. To the best of our knowledge, ocular involvement is scarcely reported in PG cases.1–5 Here, we describe a case of PG associated with necrotizing scleritis. ª 2015 The International Society of Dermatology
Figure 1 (a) An ulcer with surrounding erythema on the right thigh. (b) A scleral ulcer on the left eye International Journal of Dermatology 2015, 54, e266–e279
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e270
Correspondence
with an increased risk of mortality7 in addition to a serious threat to vision and the integrity of the eye.6,10 We think careful examination and cooperation with an ophthalmologist for ocular lesions is very important in cases of PG.
Figure 2 Dense neutrophilic infiltration in the dermis (hematoxylin and eosin stain, 9 100)
and scleritis gradually improved. Prednisolone was slowly tapered, and no recurrence has been observed for two years. Our case is peculiar in that PG was associated with scleritis in addition to UC. To our knowledge, only five cases of PG with scleritis have been reported in the English literature.1–5 Scleritis is defined as inflammation of the sclera and classified anatomically as either anterior or posterior.6 Anterior scleritis is further subdivided into diffuse, nodular, and necrotizing types. Necrotizing scleritis is the least common but the most severe type and is a significant potential threat to vision. Scleritis is also classified as either an infectious disease or a non-infectious immune-mediated disease.6 Although the pathogenesis of the latter type of scleritis is not well known, up to half of such cases have been associated with systemic disease, such as rheumatoid arthritis, Wegener’s granulomatosis, relapsing polychondritis, systemic lupus erythematosus, and IBD.7 The frequency of IBD among cases of scleritis is 2.1–4.1%.7 In a study of 243 cases of scleritis from the USA, IBD was associated in eight cases (3.3%), and PG was associated in one case (0.4%).5 As annual incidence rates of IBD and PG have been estimated at 14–29 and 0.3–1 per 100, 000 individuals in the West,8,9 respectively, the difference of frequency associated with scleritis between IBD and PG may depend on the difference of incidence rates between them. The frequency of scleritis among cases of IBD or PG is unknown. Five previous cases of PG with scleritis were not associated with IBD.1–5 In conclusion, this is a case of PG associated with both UC and anterior necrotizing scleritis. Necrotizing scleritis is a rare ocular lesion; however, it has been associated
International Journal of Dermatology 2015, 54, e266–e279
Tetsuya Hida, MD Kazutoshi Murao, MD, PhD Mika Oshima, MD Takeshi Ishigami, MD, PhD Yoshiaki Kubo, MD, PhD Department of Dermatology Institute of Health Biosciences The University of Tokushima Graduate School Tokushima Japan E-mail: [email protected]
Conflicts of interest: None. References 1 Happle R, Schiffer HP, K€ ovary PM. Ocular involvement in pyoderma gangrenosum. Arch Dermatol 1977; 113: 1612. 2 Bishop P, Tullo A. Pyoderma gangrenosum and necrotizing sclerokeratitis. Cornea 1998; 17: 346–347. 3 Braun MM, Wong IG, Ta CN. Nodular scleritis in a patient with pyoderma gangrenosum. Arch Ophthalmol 2002; 120: 1763–1765. 4 Miserocchi E, Modorati G, Foster CS, et al. Ocular and extracutaneous involvement in pyoderma gangrenosum. Ophthalmology 2002; 109: 1941–1943. 5 Akpek EK, Thorne JE, Qazi FA, et al. Evaluation of patients with scleritis for systemic disease. Ophthalmology 2004; 111: 501–506. 6 Wakefield D, Di Girolamo N, Thurau S, et al. Scleritis: Immunopathogenesis and molecular basis for therapy. Prog Retin Eye Res 2013; 35: 44–62. 7 Smith JR, Mackensen F, Rosenbaum JT. Therapy insight: scleritis and its relationship to systemic autoimmune disease. Nat Clin Pract Rheumatol 2007; 3: 219–226. 8 Cosnes J, Gower-Rousseau C, Seksik P, et al. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 2011; 140: 1785–1794. 9 Langan SM, Groves RW, Card TR, et al. Incidence, mortality, and disease associations of pyoderma gangrenosum in the United Kingdom: a retrospective cohort study. J Invest Dermatol 2012; 132: 2166–2170. 10 Okhravi N, Odufuwa B, McCluskey P, et al. Scleritis. Surv Ophthalmol 2005; 50: 351–363.
ª 2015 The International Society of Dermatology
References 1 Ximena E, del Puerto C, Mario P, et al. Ectopic extramammary Pagets disease on the face. Indian J Dermatol Venereol Leprol 2012; 78: 760–762. 2 Gal-Or N, Gil T, Amir A, et al. Management of invasive extramammary Pagets disease of the axilla—a case report. Eur J Plast Surg 2012; 35: 771–773. 3 Pierie JP, Choudry U, Muzikansky A, et al. Prognosis and management of extramammary Pagets disease and the association with secondary malignancies. J Am Coll Surg 2003; 196: 45–50. 4 Ito Y, Igawa S, Ohishi Y, et al. Prognostic indicators in 35 patients with extramammary Pagets disease. Dermatol Surg 2012; 38: 1938–1944. 5 Ohnishi T, Watanabe S. The use of cytokeratins 7 and 20 in the diagnosis of primary and secondary extramammary Pagets disease. Br J Dermatol 2000; 142: 243–247. 6 Dıaz de Le on E, Carcangiu ML, Prieto VG, et al. Extramammary Paget disease is characterized by the consistent lack of estrogen and progesterone receptors but frequently express androgen receptor. Am J Clin Pathol 2000; 113: 572–575. 7 Masuguchi S, Jinnin M, Fukushima S, et al. The expression of HER-2 in extramammary Pagets disease. BioSci Trends 2011; 5: 151–155. 8 Chang J, Prieto VG, Sangueza M, et al. Diagnostic utility of p63 expression in the differential diagnosis of pagetoid squamus cell carcinoma in situ and extramammary Paget disease: a histopathologic study of 70 cases. Am J Dermatopathol 2014; 36: 49–53. 9 Chanda JJ. Extramammary Pagets disease: prognosis and relationship to internal malignancy. J Am Acad Dermatol 1985; 13: 1009–1014. 10 McKee P. Cutaneous cyst. In: Mckee PH, Carlonje E, Brenn T, Lazar A, eds. McKee’s Pathology of the Skin, 4th edn. China: Elsevier Saunders, 2012: 1571.
A 77-year-old Japanese man was referred to our department because of a 1-month history of multiple painful skin ulcerations. He had UC controlled by salazosulfapyridine and, by the time he consulted for the skin lesions, had experienced no abdominal symptoms for at least one year. Physical examination revealed slightly painful ulcers with sharply marginated, undermined, erythematous borders on the thigh, back, nose, and scrotum (Fig. 1a). His left eye showed slight redness and a scleral ulcer (Fig. 1b). His white blood cell count and C-reactive protein were 9.2 9 103/ll and 10.79 mg/dl, respectively. Antinuclear and neutrophil cytoplasmic antibodies and rheumatoid factor were negative. A skin biopsy specimen showed dense, neutrophilic infiltration in the dermis and subcutaneous fat without granuloma or vasculitis (Fig. 2). Tissue cultures for bacteria, fungi, and mycobacteria were negative. Based on these findings, we made the diagnosis of PG. Ophthalmologists diagnosed anterior necrotizing scleritis upon ocular signs. Oral prednisone at 60 mg/day and topical clobetasol propionate treatment for the skin lesions were initiated, as was topical eye drop treatment with moxifloxacin hydrochloride, betamethasone sodium phosphate, and ofloxacin for the scleritis. The skin lesions
(a)
A case of pyoderma gangrenosum associated with anterior necrotizing scleritis in a patient with ulcerative colitis (b)
Pyoderma gangrenosum with scleritis Pyoderma gangrenosum (PG) is a chronic necrotizing inflammatory skin disease of unknown origin that presents in one of four clinical variants: ulcerative, pustular, bullous, and vegetative. More than 50% of PG cases, particularly the ulcerative PG variant, are associated with an underlying disease. Commonly associated conditions include inflammatory bowel disease (IBD) such as ulcerative colitis (UC) and Crohn’s disease, polyarthritis, hematologic diseases, and neoplasia. To the best of our knowledge, ocular involvement is scarcely reported in PG cases.1–5 Here, we describe a case of PG associated with necrotizing scleritis. ª 2015 The International Society of Dermatology
Figure 1 (a) An ulcer with surrounding erythema on the right thigh. (b) A scleral ulcer on the left eye International Journal of Dermatology 2015, 54, e266–e279
e269
e270
Correspondence
with an increased risk of mortality7 in addition to a serious threat to vision and the integrity of the eye.6,10 We think careful examination and cooperation with an ophthalmologist for ocular lesions is very important in cases of PG.
Figure 2 Dense neutrophilic infiltration in the dermis (hematoxylin and eosin stain, 9 100)
and scleritis gradually improved. Prednisolone was slowly tapered, and no recurrence has been observed for two years. Our case is peculiar in that PG was associated with scleritis in addition to UC. To our knowledge, only five cases of PG with scleritis have been reported in the English literature.1–5 Scleritis is defined as inflammation of the sclera and classified anatomically as either anterior or posterior.6 Anterior scleritis is further subdivided into diffuse, nodular, and necrotizing types. Necrotizing scleritis is the least common but the most severe type and is a significant potential threat to vision. Scleritis is also classified as either an infectious disease or a non-infectious immune-mediated disease.6 Although the pathogenesis of the latter type of scleritis is not well known, up to half of such cases have been associated with systemic disease, such as rheumatoid arthritis, Wegener’s granulomatosis, relapsing polychondritis, systemic lupus erythematosus, and IBD.7 The frequency of IBD among cases of scleritis is 2.1–4.1%.7 In a study of 243 cases of scleritis from the USA, IBD was associated in eight cases (3.3%), and PG was associated in one case (0.4%).5 As annual incidence rates of IBD and PG have been estimated at 14–29 and 0.3–1 per 100, 000 individuals in the West,8,9 respectively, the difference of frequency associated with scleritis between IBD and PG may depend on the difference of incidence rates between them. The frequency of scleritis among cases of IBD or PG is unknown. Five previous cases of PG with scleritis were not associated with IBD.1–5 In conclusion, this is a case of PG associated with both UC and anterior necrotizing scleritis. Necrotizing scleritis is a rare ocular lesion; however, it has been associated
International Journal of Dermatology 2015, 54, e266–e279
Tetsuya Hida, MD Kazutoshi Murao, MD, PhD Mika Oshima, MD Takeshi Ishigami, MD, PhD Yoshiaki Kubo, MD, PhD Department of Dermatology Institute of Health Biosciences The University of Tokushima Graduate School Tokushima Japan E-mail: [email protected]
Conflicts of interest: None. References 1 Happle R, Schiffer HP, K€ ovary PM. Ocular involvement in pyoderma gangrenosum. Arch Dermatol 1977; 113: 1612. 2 Bishop P, Tullo A. Pyoderma gangrenosum and necrotizing sclerokeratitis. Cornea 1998; 17: 346–347. 3 Braun MM, Wong IG, Ta CN. Nodular scleritis in a patient with pyoderma gangrenosum. Arch Ophthalmol 2002; 120: 1763–1765. 4 Miserocchi E, Modorati G, Foster CS, et al. Ocular and extracutaneous involvement in pyoderma gangrenosum. Ophthalmology 2002; 109: 1941–1943. 5 Akpek EK, Thorne JE, Qazi FA, et al. Evaluation of patients with scleritis for systemic disease. Ophthalmology 2004; 111: 501–506. 6 Wakefield D, Di Girolamo N, Thurau S, et al. Scleritis: Immunopathogenesis and molecular basis for therapy. Prog Retin Eye Res 2013; 35: 44–62. 7 Smith JR, Mackensen F, Rosenbaum JT. Therapy insight: scleritis and its relationship to systemic autoimmune disease. Nat Clin Pract Rheumatol 2007; 3: 219–226. 8 Cosnes J, Gower-Rousseau C, Seksik P, et al. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 2011; 140: 1785–1794. 9 Langan SM, Groves RW, Card TR, et al. Incidence, mortality, and disease associations of pyoderma gangrenosum in the United Kingdom: a retrospective cohort study. J Invest Dermatol 2012; 132: 2166–2170. 10 Okhravi N, Odufuwa B, McCluskey P, et al. Scleritis. Surv Ophthalmol 2005; 50: 351–363.
ª 2015 The International Society of Dermatology
