Letters to the Editor
3 Sviggum HP, Davis MD, Rajkumar SV et al. Dermatologic adverse effects of lenalidomide therapy for amyloidosis and multiple myeloma. Arch Dermatol 2006; 142: 1298–1302. 4 Phillips J, Kujawa J, Davis-Lorton M, Hindenburg A. Successful desensitization in a patient with lenalidomide hypersensitivity. Am J Hematol 2007; 82: 1030.
5 Seki JT, Banglawala S, Lentz EM, Reece DE. Desensitization to lenalidomide in a patient with relapsed multiple myeloma. Clin Lymphoma Myeloma Leuk 2013; 13: 162–165.
Unusually extensive disseminated herpes zoster with multiple ulcer formation in a methotrexate-treated rheumatoid arthritis patient Dear Editor, The risk for viremia and visceral dissemination of herpes zoster (HZ) in patients taking immunosuppressive therapy has been reported to be high, however, the incidence of fatal recurrent varicella zoster virus (VZV) infection is low.1 Here, we reported an unusually extensive case of disseminated HZ
(a)
with multiple severe ulcers, who had been treated with immunosuppressives, including methotrexate (MTX), and had multiple episodes of HZ. Despite intensive antiviral treatment, the patient developed VZV viremia and eventually died, emphasizing the necessity of preemptive management of VZV.
(b)
(d)
(c)
(e)
Figure 1. Clinical manifestations and histopathological findings. (a) Multiple, hemorrhagic and bullous lesions with ulcers of her bilateral lower extremities. (b) Hemorrhagic lesion becoming necrotic from the center on the right knee. (c) Gangrenous ulcer covered with thick crusts of the left leg. (d) Ballooning degeneration and acantholysis in an intraepidermal vesicle (hematoxylin–eosin, original magnification 9100). (e) Dense neutrophilic infiltration with extravasation and fibrin deposition on the blood vessel wall of the mid-dermis (hematoxylin–eosin, original magnification 9200).
Correspondence: Manabu Ohyama, M.D., Ph.D., Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjukuku, Tokyo 160-8582, Japan. Email: [email protected]
© 2014 Japanese Dermatological Association
181
Letters to the Editor
An 84-year-old Japanese woman with vesicles/blisters and severely painful ulcers, which started to spread from the left leg 1.5 month prior to her visit, was referred to our clinic. Her medical history included rheumatoid arthritis (RA) treated with MTX 5 mg/week, mizoribine 100 mg/day and prednisolone 5 mg/day for 20 years and four episodes of HZ. On physical examination, multiple, hemorrhagic and vesicular/bullous lesions with gangrenous ulcers were observed on her bilateral lower extremities (Fig. 1a–c). Similar lesions were noticed on the left arm, left buttock and face. Laboratory tests detected moderately decreased white cell count (3300/lL), including lymphocytes (211/lL) and mild anemia (hemoglobin 11.0 g/dL). Serum Immunoglobulin G level was normal, however, anti-VZV antibody titer was not increased. The swabs obtained from vesicles detected VZV. A biopsy specimen of a bulla on the thigh demonstrated intraepidermal blister with ballooning degeneration and acantholysis (Fig. 1d). Perivascular dense neutrophilic infiltration with extravasation and fibrin deposition on blood vessel walls were observed in the mid-dermis (Fig. 1f). The diagnosis of disseminated HZ was made. Acyclovir 500 mg/day was administrated i.v. for 5 days, followed by 750 mg/day for an additional 4 days. As the spread of lesion stopped, acyclovir was terminated. One week after, most lesions remained unchanged and blood test detected atypical lymphocytes (2205/lL) and VZV DNA (290 copies/105 peripheral blood mononuclear cells by real-time polymerase chain reaction), indicating viremia. Cytomegalovirus antigenemia tests were negative and no sign of Epstein–Barr virus reactivation was detected during the course. Additional administration of vidarabine (300 mg/day) reduced atypical lymphocytes but failed to recover her general condition. Eventually, she died on day 38. Decline of VZV-specific memory T cells has been reported in relation to age, RA and immunosuppression.2,3 In our case, anti-VZV antibody titer was not elevated despite recurrent HZ episodes, suggesting impaired immunity against VZV secondary to long-term RA and its treatment. Virological investigation denied possible contribution of acyclovir-resistant VZV clone. A previous study elucidated that VZV could trigger leukocytoclastic vasculitis.4 However, a case of HZ with similar manifestations was not found in the published work, implying that
impaired immunity against VZV alone is insufficient to explain the condition of our case. Indeed, immunohistochemical study failed to detect VZV antigen in vessel walls (data not shown). An additional mechanism causing damage to vasculature, such as rheumatoid vasculitis, might have contributed to the pathophysiology. The Advisory Committee on Immunization Practices recommended the administration of VZV vaccination to autoinflammatory disease patients receiving low-dose steroids and immunosuppressives.5 Preemptive vaccination sufficient to elicit immunity may be encouraged, especially to RA patients before immunosuppressive therapy is started.
CONFLICT OF INTEREST:
None.
Risa KAKUTA,1 Utako OKATA,1 Takeru FUNAKOSHI,1 Yumi FUJIO,1 Naoki INOUE,2 Shinichi TAKAHASHI,3 Masayuki AMAGAI,1 Manabu OHYAMA1 1 Departments of Dermatology, Keio University School of Medicine, Department of Virology I, National Institute of Infectious Disease, Tokyo, and 3Department of Dermatology, Ichikawa General Hospital, Tokyo Dental College, Ichikawa, Japan 2
doi: 10.1111/1346-8138.12377
REFERENCES 1 Arvin AM. Varicella-zoster virus. Clin Microbiol Rev 1996; 9: 361– 381. 2 Yamaguchi Y, Kohei N, Yoshifumi T et al. Herpes zoster in connective tissue diseases: rherumatoid arthritis and mixed connective tissue disease in comparison with systemic lupus erythematosus. Kansenshogaku Zasshi 1991; 65: 1389–1393. 3 Arvin AM. Humoral and cellular immunity to varicella-zoster virus: an overview. J Infect Dis 2008; 197: S58–S60. 4 Ryoichi M, Toru B, Takuya I et al. Immunohistochemical study of skin lesions in herpes zoster. Virchows Arch A Pathol Anat Histopathol 1992; 420: 71–76. 5 Herpaz R, Ortega-Sanchez IR, Seward JF et al. Recommendation of the advisory committee on immunization practice (ACIP). MMWR Recomm Rep 2008; 57: 1–30.
Hapten-induced lymphadenosis benigna cutis secondary to squaric acid dibutylester sensitization for alopecia areata Dear Editor, Lymphadenosis benigna cutis (LABC) represents induced ectopic lymphoid tissues caused by external stimuli, such as insect bites or infection.1 However, exact triggers often remain un-
identifiable. Here, we present a rare and instructive case of LABC triggered by squaric acid dibutylester (SADBE) sensitization for the treatment of alopecia areata (AA), which required surgical resection.
Correspondence: Manabu Ohyama, M.D., Ph.D., Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku Tokyo 160-8582, Japan. Email: [email protected]
182
© 2014 Japanese Dermatological Association
3 Sviggum HP, Davis MD, Rajkumar SV et al. Dermatologic adverse effects of lenalidomide therapy for amyloidosis and multiple myeloma. Arch Dermatol 2006; 142: 1298–1302. 4 Phillips J, Kujawa J, Davis-Lorton M, Hindenburg A. Successful desensitization in a patient with lenalidomide hypersensitivity. Am J Hematol 2007; 82: 1030.
5 Seki JT, Banglawala S, Lentz EM, Reece DE. Desensitization to lenalidomide in a patient with relapsed multiple myeloma. Clin Lymphoma Myeloma Leuk 2013; 13: 162–165.
Unusually extensive disseminated herpes zoster with multiple ulcer formation in a methotrexate-treated rheumatoid arthritis patient Dear Editor, The risk for viremia and visceral dissemination of herpes zoster (HZ) in patients taking immunosuppressive therapy has been reported to be high, however, the incidence of fatal recurrent varicella zoster virus (VZV) infection is low.1 Here, we reported an unusually extensive case of disseminated HZ
(a)
with multiple severe ulcers, who had been treated with immunosuppressives, including methotrexate (MTX), and had multiple episodes of HZ. Despite intensive antiviral treatment, the patient developed VZV viremia and eventually died, emphasizing the necessity of preemptive management of VZV.
(b)
(d)
(c)
(e)
Figure 1. Clinical manifestations and histopathological findings. (a) Multiple, hemorrhagic and bullous lesions with ulcers of her bilateral lower extremities. (b) Hemorrhagic lesion becoming necrotic from the center on the right knee. (c) Gangrenous ulcer covered with thick crusts of the left leg. (d) Ballooning degeneration and acantholysis in an intraepidermal vesicle (hematoxylin–eosin, original magnification 9100). (e) Dense neutrophilic infiltration with extravasation and fibrin deposition on the blood vessel wall of the mid-dermis (hematoxylin–eosin, original magnification 9200).
Correspondence: Manabu Ohyama, M.D., Ph.D., Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjukuku, Tokyo 160-8582, Japan. Email: [email protected]
© 2014 Japanese Dermatological Association
181
Letters to the Editor
An 84-year-old Japanese woman with vesicles/blisters and severely painful ulcers, which started to spread from the left leg 1.5 month prior to her visit, was referred to our clinic. Her medical history included rheumatoid arthritis (RA) treated with MTX 5 mg/week, mizoribine 100 mg/day and prednisolone 5 mg/day for 20 years and four episodes of HZ. On physical examination, multiple, hemorrhagic and vesicular/bullous lesions with gangrenous ulcers were observed on her bilateral lower extremities (Fig. 1a–c). Similar lesions were noticed on the left arm, left buttock and face. Laboratory tests detected moderately decreased white cell count (3300/lL), including lymphocytes (211/lL) and mild anemia (hemoglobin 11.0 g/dL). Serum Immunoglobulin G level was normal, however, anti-VZV antibody titer was not increased. The swabs obtained from vesicles detected VZV. A biopsy specimen of a bulla on the thigh demonstrated intraepidermal blister with ballooning degeneration and acantholysis (Fig. 1d). Perivascular dense neutrophilic infiltration with extravasation and fibrin deposition on blood vessel walls were observed in the mid-dermis (Fig. 1f). The diagnosis of disseminated HZ was made. Acyclovir 500 mg/day was administrated i.v. for 5 days, followed by 750 mg/day for an additional 4 days. As the spread of lesion stopped, acyclovir was terminated. One week after, most lesions remained unchanged and blood test detected atypical lymphocytes (2205/lL) and VZV DNA (290 copies/105 peripheral blood mononuclear cells by real-time polymerase chain reaction), indicating viremia. Cytomegalovirus antigenemia tests were negative and no sign of Epstein–Barr virus reactivation was detected during the course. Additional administration of vidarabine (300 mg/day) reduced atypical lymphocytes but failed to recover her general condition. Eventually, she died on day 38. Decline of VZV-specific memory T cells has been reported in relation to age, RA and immunosuppression.2,3 In our case, anti-VZV antibody titer was not elevated despite recurrent HZ episodes, suggesting impaired immunity against VZV secondary to long-term RA and its treatment. Virological investigation denied possible contribution of acyclovir-resistant VZV clone. A previous study elucidated that VZV could trigger leukocytoclastic vasculitis.4 However, a case of HZ with similar manifestations was not found in the published work, implying that
impaired immunity against VZV alone is insufficient to explain the condition of our case. Indeed, immunohistochemical study failed to detect VZV antigen in vessel walls (data not shown). An additional mechanism causing damage to vasculature, such as rheumatoid vasculitis, might have contributed to the pathophysiology. The Advisory Committee on Immunization Practices recommended the administration of VZV vaccination to autoinflammatory disease patients receiving low-dose steroids and immunosuppressives.5 Preemptive vaccination sufficient to elicit immunity may be encouraged, especially to RA patients before immunosuppressive therapy is started.
CONFLICT OF INTEREST:
None.
Risa KAKUTA,1 Utako OKATA,1 Takeru FUNAKOSHI,1 Yumi FUJIO,1 Naoki INOUE,2 Shinichi TAKAHASHI,3 Masayuki AMAGAI,1 Manabu OHYAMA1 1 Departments of Dermatology, Keio University School of Medicine, Department of Virology I, National Institute of Infectious Disease, Tokyo, and 3Department of Dermatology, Ichikawa General Hospital, Tokyo Dental College, Ichikawa, Japan 2
doi: 10.1111/1346-8138.12377
REFERENCES 1 Arvin AM. Varicella-zoster virus. Clin Microbiol Rev 1996; 9: 361– 381. 2 Yamaguchi Y, Kohei N, Yoshifumi T et al. Herpes zoster in connective tissue diseases: rherumatoid arthritis and mixed connective tissue disease in comparison with systemic lupus erythematosus. Kansenshogaku Zasshi 1991; 65: 1389–1393. 3 Arvin AM. Humoral and cellular immunity to varicella-zoster virus: an overview. J Infect Dis 2008; 197: S58–S60. 4 Ryoichi M, Toru B, Takuya I et al. Immunohistochemical study of skin lesions in herpes zoster. Virchows Arch A Pathol Anat Histopathol 1992; 420: 71–76. 5 Herpaz R, Ortega-Sanchez IR, Seward JF et al. Recommendation of the advisory committee on immunization practice (ACIP). MMWR Recomm Rep 2008; 57: 1–30.
Hapten-induced lymphadenosis benigna cutis secondary to squaric acid dibutylester sensitization for alopecia areata Dear Editor, Lymphadenosis benigna cutis (LABC) represents induced ectopic lymphoid tissues caused by external stimuli, such as insect bites or infection.1 However, exact triggers often remain un-
identifiable. Here, we present a rare and instructive case of LABC triggered by squaric acid dibutylester (SADBE) sensitization for the treatment of alopecia areata (AA), which required surgical resection.
Correspondence: Manabu Ohyama, M.D., Ph.D., Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku Tokyo 160-8582, Japan. Email: [email protected]
182
© 2014 Japanese Dermatological Association
