- Email: [email protected]
Treatment of pyostomatitis vegetans with topical tacrolimus
722 Letters
J AM ACAD DERMATOL APRIL 2005
Juntendo University School of Medicine Inforward Incc Tokyo, Japan Correspondence to: Kayako Hira, MD Department of Dermatology Juntendo University School of Medicine 2-1-1, Hongo, Bunkyo-ku Tokyo 113-8421, Japan E-mail: [email protected] REFERENCES 1. Manabe T, Inagaki Y, Nakagawa S, Miyoshi K, Ueki H. Ripple pigmentation of the neck in atopic dermatitis. Am J Dermatopathol 1987;9:301-7. 2. Hayashi N, Fukunaka H, Wakugawa M, Nakamura K, Tamaki K. Topical hydroquinone treatment for atopic dirty neck. Nishinihon Hifuka 2000;62:668-71. 3. Allen BR. Tacrolimus ointment: its place in the therapy of atopic dermatitis. J Allergy Clin Immunol 2002;109:401-3. 4. Fullerton A, Fischer T, Lahti A, Wilhelm KP, Takiiwaki H, Serup J. Guidelines for measurement of skin colour and erythema: a report from the standardization group of the European Society of Contact Dermatitis. Contact Dermatitis 1996;35:1-10. 5. Lee JY, Kang WH. Effect of cyclosporin A on melanogenesis in cultured human melanocytes. Pigment Cell Res 2003;16:504-8. 6. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Dermatol Venereol 1980;(suppl 92):44-7.
doi:10.1016/j.jaad.2004.10.860
Fig 1. Prominent fissured, soft, velvety plaques on the patient’s lower lip.
Fig 2. Resolution of plaques after topical tacrolimus therapy.
CASE REPORT Treatment of pyostomatitis vegetans with topical tacrolimus To the Editor: Pyostomatitis vegetans is a rare, debilitating disorder of the oral mucosa often found in association with inflammatory bowel disease, most commonly ulcerative colitis.1-5 When cutaneous lesions are present, the condition is referred to as pyodermatitis-pyostomatitis vegetans. The conventional treatments described in the literature to date are either ineffective or have significant drawbacks. Because of the rarity of this condition, no doubleblinded, randomized, controlled trials have been performed to evaluate the different modalities, and thus the evidence for the efficacy, safety, and tolerability of each of these treatments is anecdotal. In this paper, we report a case of pyostomatitis vegetans that responded quickly and dramatically to treatment with 0.1% tacrolimus ointment (Protopic; Fujisawa Healthcare Inc, Deerfield, Ill) applied twice daily. No significant side effects were noted. Our experience suggests that this represents a novel and potentially useful therapeutic option for patients with this condition.
A 30-year-old woman presented to our clinic with a 6-week history of a widespread, painful eruption in her mouth. She complained of progressive difficulty eating, prominent swelling of the lips, particularly the lower one, and nighttime drooling. She was in good overall health and denied any drug allergies. The patient had no history of inflammatory bowel disease, but said that she did experience intermittent abdominal pain, chronic diarrhea, and occasional blood in her stool. She also complained of intermittent redness, pruritus, and pain in her eyes. On examination, she was found to have prominent thickening of her lower lip with spongy, fissured, velvety plaques encompassing the majority of her labial mucosa (Fig 1). One linear ‘‘snail track’’ erosion was noted on the left upper gingival surface, and another was located on the floor of her mouth under the tongue. The tongue itself was unaffected. The lesions were mildly tender. Routine histopathologic examination revealed marked spongiosis, mixed inflammation, including neutrophils and numerous eosinophils, and multiple microabscesses. No granulomas were seen. Periodic acideSchiff (PAS) stains were negative for fungal elements. Direct immunofluorescence studies ruled
J AM ACAD DERMATOL VOLUME 52, NUMBER 4
out pemphigus vulgaris and pemphigus vegetans. She was referred for colonoscopy, which showed widespread ulcerative colitis. The patient had initially been seen by her primary care provider and treated with a 1-week course of nystatin (swish and swallow) 4 times per day for a presumed oral Candida infection; no improvement was noted with this regimen. Upon evaluation in our clinic, this was discontinued and she was switched to tacrolimus 0.1% ointment to the affected areas twice per day while a more extensive work-up was pursued. Her lips improved within 1 to 2 weeks (Fig 2), and she was able to discontinue application of the medication in this area. The other ulcerations proved more recalcitrant, however, and required an additional 1 to 2 weeks to clear. Over the next few months, she noted new oral lesions in several areas of her mouth; these responded to treatment in a similar fashion. After her colonoscopy, she was placed on mesalamine for her ulcerative colitis; her gastrointestinal symptoms improved substantially after initiation of this regimen, and no new oral lesions have appeared. Andrew E. Werchniak, MDa Craig A. Storm, MDb Richard W. Plunkett, PhDc Ernst H. Beutner, PhDc James G. H. Dinulos, MDd Department of Dermatologya Harvard Medical School and Brigham & Women’s Hospital Boston, Massachusetts Department of Pathologyb Assistant Professor of Medicine and Pediatrics (Dermatology)d Dartmouth Medical School and Dartmouth-Hitchcock Medical Center Hanover and Lebanon, New Hampshire Departments of Microbiology and Dermatologyc State University of New York at Buffalo and Beutner Laboratories Buffalo, New York Correspondence to: Andrew E. Werchniak, MD Brigham Dermatology Associates 221 Longwood Ave, Boston, MA 02115 E-mail: [email protected] REFERENCES 1. Hegarty AM, Barrett AW, Scully C. Pyostomatitis vegetans. Clin Exp Dermatol 2004;29:1-7. 2. Soriano ML, Martinez N, Grilli R, Farina MC, Martin L, Requena L. Pyodermatitis-pyostomatitis vegetans: report of a case and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:322-6.
Letters 723
3. Nigen S, Poulin Y, Rochette L, Levesque MH, Gagne E. Pyodermatitis-pyostomatitis vegetans: two cases and a review of the literature. J Cutan Med Surg 2003;7:250-5. 4. Mehravaran M, Kemeny L, Husz S, Korom I, Kiss M, Dobozy A. Pyodermatitis-pyostomatitis vegetans. Br J Dermatol 1997;137: 266-9. 5. Storwick GS, Prihoda MB, Fulton RJ, Wood WS. Pyodermatitispyostomatitis vegetans: a specific marker for inflammatory bowel disease. J Am Acad Dermatol 1994;31:336-41. doi:10.1016/j.jaad.2004.11.041
Three cases of Bowen’s disease on the lower abdomen associated with high-risk types 16, 33, and 59 of human papillomavirus To the Editor: Bowen’s disease (BD) of the genitalia and fingers has generally been accepted to be associated with high-risk types of human papillomavirus (HPV) infection, and there have recently been several case reports of HPV-associated BD on other locations.1 We describe three male patients with BD on the lower abdomen associated with high-risk types of HPV infection. Case 1 was a 69-year-old Japanese man who presented with an erythematous plaque on the lower abdomen. Histologically, the lesions showed full-thickness epidermal atypia. The atypical keratinocytes showed hyperchromatic nuclei, mitotic figures, and clumping of nuclear chromatin. Case 2 was a 79-year-old Japanese man who presented with a 1-year history of an erythematous plaque on his lower abdomen, and case 3 was a 71-year-old Japanese man who presented with an erythematous plaque adjacent to the penis. The histologic findings of all 3 cases were compatible with those of BD. Because the lesions were located very close to the genitalia, we tried to detect the presence of HPV DNA in the lesions by polymerase chain reaction (PCR) with HPV-specific primers as described.2,3 Each of the amplified PCR products yielded a positive band of approximately 250 base pairs. The types of HPV from cases 1 and 2 were identified as 16 and 33, respectively, on the basis of the PCR-restriction fragment length polymorphisms (RFLP).2,3 On the other hand, the type of HPV from case 3 was identified as 59, not by RFLP but by DNA sequencing. The partial sequence of PCR product from case 3 was completely identical to the sequence of L1 open reading frame from HPV type 59 (GenBank accession number NC001635). HPV type 59 was initially cloned from vulvar intraepithelial neoplasia,4 and the HPV 59 genome has close homology with HPV 18, 45, and 39, all 3 belonging to the high-risk group.4,5 Although HPV
J AM ACAD DERMATOL APRIL 2005
Juntendo University School of Medicine Inforward Incc Tokyo, Japan Correspondence to: Kayako Hira, MD Department of Dermatology Juntendo University School of Medicine 2-1-1, Hongo, Bunkyo-ku Tokyo 113-8421, Japan E-mail: [email protected] REFERENCES 1. Manabe T, Inagaki Y, Nakagawa S, Miyoshi K, Ueki H. Ripple pigmentation of the neck in atopic dermatitis. Am J Dermatopathol 1987;9:301-7. 2. Hayashi N, Fukunaka H, Wakugawa M, Nakamura K, Tamaki K. Topical hydroquinone treatment for atopic dirty neck. Nishinihon Hifuka 2000;62:668-71. 3. Allen BR. Tacrolimus ointment: its place in the therapy of atopic dermatitis. J Allergy Clin Immunol 2002;109:401-3. 4. Fullerton A, Fischer T, Lahti A, Wilhelm KP, Takiiwaki H, Serup J. Guidelines for measurement of skin colour and erythema: a report from the standardization group of the European Society of Contact Dermatitis. Contact Dermatitis 1996;35:1-10. 5. Lee JY, Kang WH. Effect of cyclosporin A on melanogenesis in cultured human melanocytes. Pigment Cell Res 2003;16:504-8. 6. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Dermatol Venereol 1980;(suppl 92):44-7.
doi:10.1016/j.jaad.2004.10.860
Fig 1. Prominent fissured, soft, velvety plaques on the patient’s lower lip.
Fig 2. Resolution of plaques after topical tacrolimus therapy.
CASE REPORT Treatment of pyostomatitis vegetans with topical tacrolimus To the Editor: Pyostomatitis vegetans is a rare, debilitating disorder of the oral mucosa often found in association with inflammatory bowel disease, most commonly ulcerative colitis.1-5 When cutaneous lesions are present, the condition is referred to as pyodermatitis-pyostomatitis vegetans. The conventional treatments described in the literature to date are either ineffective or have significant drawbacks. Because of the rarity of this condition, no doubleblinded, randomized, controlled trials have been performed to evaluate the different modalities, and thus the evidence for the efficacy, safety, and tolerability of each of these treatments is anecdotal. In this paper, we report a case of pyostomatitis vegetans that responded quickly and dramatically to treatment with 0.1% tacrolimus ointment (Protopic; Fujisawa Healthcare Inc, Deerfield, Ill) applied twice daily. No significant side effects were noted. Our experience suggests that this represents a novel and potentially useful therapeutic option for patients with this condition.
A 30-year-old woman presented to our clinic with a 6-week history of a widespread, painful eruption in her mouth. She complained of progressive difficulty eating, prominent swelling of the lips, particularly the lower one, and nighttime drooling. She was in good overall health and denied any drug allergies. The patient had no history of inflammatory bowel disease, but said that she did experience intermittent abdominal pain, chronic diarrhea, and occasional blood in her stool. She also complained of intermittent redness, pruritus, and pain in her eyes. On examination, she was found to have prominent thickening of her lower lip with spongy, fissured, velvety plaques encompassing the majority of her labial mucosa (Fig 1). One linear ‘‘snail track’’ erosion was noted on the left upper gingival surface, and another was located on the floor of her mouth under the tongue. The tongue itself was unaffected. The lesions were mildly tender. Routine histopathologic examination revealed marked spongiosis, mixed inflammation, including neutrophils and numerous eosinophils, and multiple microabscesses. No granulomas were seen. Periodic acideSchiff (PAS) stains were negative for fungal elements. Direct immunofluorescence studies ruled
J AM ACAD DERMATOL VOLUME 52, NUMBER 4
out pemphigus vulgaris and pemphigus vegetans. She was referred for colonoscopy, which showed widespread ulcerative colitis. The patient had initially been seen by her primary care provider and treated with a 1-week course of nystatin (swish and swallow) 4 times per day for a presumed oral Candida infection; no improvement was noted with this regimen. Upon evaluation in our clinic, this was discontinued and she was switched to tacrolimus 0.1% ointment to the affected areas twice per day while a more extensive work-up was pursued. Her lips improved within 1 to 2 weeks (Fig 2), and she was able to discontinue application of the medication in this area. The other ulcerations proved more recalcitrant, however, and required an additional 1 to 2 weeks to clear. Over the next few months, she noted new oral lesions in several areas of her mouth; these responded to treatment in a similar fashion. After her colonoscopy, she was placed on mesalamine for her ulcerative colitis; her gastrointestinal symptoms improved substantially after initiation of this regimen, and no new oral lesions have appeared. Andrew E. Werchniak, MDa Craig A. Storm, MDb Richard W. Plunkett, PhDc Ernst H. Beutner, PhDc James G. H. Dinulos, MDd Department of Dermatologya Harvard Medical School and Brigham & Women’s Hospital Boston, Massachusetts Department of Pathologyb Assistant Professor of Medicine and Pediatrics (Dermatology)d Dartmouth Medical School and Dartmouth-Hitchcock Medical Center Hanover and Lebanon, New Hampshire Departments of Microbiology and Dermatologyc State University of New York at Buffalo and Beutner Laboratories Buffalo, New York Correspondence to: Andrew E. Werchniak, MD Brigham Dermatology Associates 221 Longwood Ave, Boston, MA 02115 E-mail: [email protected] REFERENCES 1. Hegarty AM, Barrett AW, Scully C. Pyostomatitis vegetans. Clin Exp Dermatol 2004;29:1-7. 2. Soriano ML, Martinez N, Grilli R, Farina MC, Martin L, Requena L. Pyodermatitis-pyostomatitis vegetans: report of a case and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:322-6.
Letters 723
3. Nigen S, Poulin Y, Rochette L, Levesque MH, Gagne E. Pyodermatitis-pyostomatitis vegetans: two cases and a review of the literature. J Cutan Med Surg 2003;7:250-5. 4. Mehravaran M, Kemeny L, Husz S, Korom I, Kiss M, Dobozy A. Pyodermatitis-pyostomatitis vegetans. Br J Dermatol 1997;137: 266-9. 5. Storwick GS, Prihoda MB, Fulton RJ, Wood WS. Pyodermatitispyostomatitis vegetans: a specific marker for inflammatory bowel disease. J Am Acad Dermatol 1994;31:336-41. doi:10.1016/j.jaad.2004.11.041
Three cases of Bowen’s disease on the lower abdomen associated with high-risk types 16, 33, and 59 of human papillomavirus To the Editor: Bowen’s disease (BD) of the genitalia and fingers has generally been accepted to be associated with high-risk types of human papillomavirus (HPV) infection, and there have recently been several case reports of HPV-associated BD on other locations.1 We describe three male patients with BD on the lower abdomen associated with high-risk types of HPV infection. Case 1 was a 69-year-old Japanese man who presented with an erythematous plaque on the lower abdomen. Histologically, the lesions showed full-thickness epidermal atypia. The atypical keratinocytes showed hyperchromatic nuclei, mitotic figures, and clumping of nuclear chromatin. Case 2 was a 79-year-old Japanese man who presented with a 1-year history of an erythematous plaque on his lower abdomen, and case 3 was a 71-year-old Japanese man who presented with an erythematous plaque adjacent to the penis. The histologic findings of all 3 cases were compatible with those of BD. Because the lesions were located very close to the genitalia, we tried to detect the presence of HPV DNA in the lesions by polymerase chain reaction (PCR) with HPV-specific primers as described.2,3 Each of the amplified PCR products yielded a positive band of approximately 250 base pairs. The types of HPV from cases 1 and 2 were identified as 16 and 33, respectively, on the basis of the PCR-restriction fragment length polymorphisms (RFLP).2,3 On the other hand, the type of HPV from case 3 was identified as 59, not by RFLP but by DNA sequencing. The partial sequence of PCR product from case 3 was completely identical to the sequence of L1 open reading frame from HPV type 59 (GenBank accession number NC001635). HPV type 59 was initially cloned from vulvar intraepithelial neoplasia,4 and the HPV 59 genome has close homology with HPV 18, 45, and 39, all 3 belonging to the high-risk group.4,5 Although HPV