- Email: [email protected]
Treatment of nephrogenic systemic fibrosis with Re-PUVA
Letters S39
J AM ACAD DERMATOL VOLUME 59, NUMBER 2
Fig 2. A, Section of skin biopsy specimen showing chronic granulomatous inflammation. (Hematoxylin-eosin stain; original magnification: 3200.) B, There are fungal spores in granuloma. (Gomori methenamine silver stain; original magnification: 3400.) REFERENCES 1. Paphitou NI, Ostrosky-Zeichner L, Paetznick VL, Rodriguez JR, Chen E, Rex JH. In vitro antifungal susceptibilities of Trichosporon species. Antimicrob Agents Chemother 2002;46:1144-6. 2. Yang R, Ao J, Wang W, Song K, Li R, Wang D. Disseminated trichosporonosis in China. Mycoses 2003;46:519-23. 3. Ebright JR, Fairfax MR, Vazquez JA. Trichosporon asahii, a nonCandida yeast that caused fatal septic shock in a patient without cancer or neutropenia. Clin Infect Dis 2001;33:e28-30. 4. Pulvirenti N, Dall’Oglio F, Greco AM, Oliveri S, Schwartz RA, Micali G. Superficial cutaneous Trichosporon asahii infection in an immunocompetent host. Int J Dermatol 2006;45: 1428-31. 5. Yun SJ, Lee JB, Shin MG, Kim SJ, Won YH, Lee SC. Cutaneous abscess by Trichosporon asahii developing on a steroid injection site in a healthy adult. Clin Dermatol 2005;31:545-7. doi:10.1016/j.jaad.2007.08.017
Treatment of nephrogenic systemic fibrosis with Re-PUVA To the Editor: Nephrogenic systemic fibrosis (NSF) is a rare fibrosing systemic disease, first recognized in 20001 that affects patients with renal insufficiency or renal failure. No single therapeutic regimen has been universally successful in treating this progressive fibrotic disease. We report significant clinical
Fig 1. Case 1. Patient with maximal flexion of digits before therapy (A) and 11 months after initiating therapy (B).
improvement in two cases of NSF with psoralens plus ultraviolet A (PUVA) plus retinoid treatment. Case 1. A 49-year-old male patient with NSF and receiving hemodialysis in whom conservative treatment had failed was started on a PUVA and retinoid (Re-PUVA) regimen. After 15 PUVA treatments (16.0 J/6:40 min/133 total J) and 11 weeks of acitretin (12.5 mg), the patient began noticing softening of the involved skin, a greater ability to clench his fist, and increased joint mobility with an approximate 60% improvement over baseline (Fig 1). He improved considerably after receiving a new kidney; however, after subsequent graft rejection, his disease returned. Within 2 months PUVA and acitretin therapy was restarted, and the patient again experienced softening of plaques. He has received a total of 123 PUVA treatments, receiving a total of 1756 J, and has maintained benefit and functionality.
S40 Letters
J AM ACAD DERMATOL AUGUST 2008
We recognize there has been a previous unsuccessful report of a patient who started retinoid-PUVA therapy, but treatments were stopped after 1 month because of muscle pain and lack of dermatologic improvement.5 Our first patient did not improve until week 5 of combined Re-PUVA treatment and our second patient did not have significant improvement until at least 4 weeks of combined therapy. With the dismal prognosis of this progressive disease and the dramatic clinical response of our two patients, we believe Re-PUVA therapy might be a viable, relatively safe, treatment option to improve functionality and quality of life in these patients. Keith L. Duffy, MD, Layne Green, MD, Ronald Harris, MD, MBA, and Douglas Powell, MD Department of Dermatology, University of Utah, Salt Lake City Funding sources: None. Conflicts of interest: None declared. Fig 2. Case 2. Medial aspect of left thigh before treatment (A) and after 6 months of combined therapy (B).
Reprint request: Douglas Powell, MD, University of Utah, Department of Dermatology, 30 N 1900 E, School of Medicine 4B454, Salt Lake City, UT 84132
Case 2. A 54-year-old female hemodialysis patient with NSF/nephrogenic fibrosing dermopathy had progressive disease after 2 months of physical therapy and was started on a regimen of acitretin (10 mg every other day) and PUVA. Initial improvement was noted after 10 PUVA treatments (9.0 J/3:45 min/38.5 total J); over the following 2 months the mobility in her left knee improved substantially with impressive softening of the plaques maximized after approximately 6 months (Fig 2). After 12 months of combined therapy consisting of 70 PUVA treatments, totaling 1202 J, she continues to have small but clinically significant alleviation of her disease. Comment. Recent reports suggest that gadolinium may be the etiologic agent that triggers the fibrotic cascade in NSF.2,3 Retrospectively we were able to confirm gadolinium exposure, specifically to gadodiamide (Omniscan, GE Healthcare, Princeton, NJ), in both patients. Exposure to clinical disease was approximately 4 months in our first patient and 2 weeks in our second patient. Brenner et al,4 in a review of PUVA in fibrosing skin disease, showed clearly there is proven benefit in morphea and scleroderma and questionable benefit in scleromyxedema. The mechanism of how exactly PUVA therapy is successful in treating sclerotic skin diseases has not been fully elucidated, but it is thought that PUVA acts either by inhibiting procollagen synthesis or by reducing the amount of transforming growth factor b-1.
E-mail: [email protected] REFERENCES 1. Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE. Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 2000;365:1000-1. 2. Grobner T. Gadolinium—a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 2006;21:1104-8. 3. USFDA Healthcare professional sheet — Gadolinium-containing contrast agents for Magnetic Resonance Imaging (MRI) FDA alert 06/2006. Development of serious and sometimes fatal nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy. Available at: www.fda.gov/cder/drugInfoSheets/HCP/gccaHCP.htm. 4. Brenner M, Herzinger T, Berking C, Plewig G, Degitz K. Phototherapy and photochemotherapy of sclerosing skin diseases. Photodermatol Photoimmunol Photomed 2005;21:157-65. 5. Lauchli S, Zortea-Caflisch C, Nestle FO, Burg G, Kempf W. Nephrogenic fibrosing dermopathy treated with extracorporeal photopheresis. Dermatology 2004;208:278-80. doi:10.1016/j.jaad.2007.08.035
Common variable immunodeficiency presenting as chronic urticaria To the Editor: A 15-year-old white boy presented with a 4-month history of daily pruritic hives, affecting his hands, feet, and legs. Medical history was significant for occasional repeated ear and sinus infections since age 8. Combined antihistamines provided minimal clinical response. A skin biopsy specimen demonstrated mild papillary dermal
J AM ACAD DERMATOL VOLUME 59, NUMBER 2
Fig 2. A, Section of skin biopsy specimen showing chronic granulomatous inflammation. (Hematoxylin-eosin stain; original magnification: 3200.) B, There are fungal spores in granuloma. (Gomori methenamine silver stain; original magnification: 3400.) REFERENCES 1. Paphitou NI, Ostrosky-Zeichner L, Paetznick VL, Rodriguez JR, Chen E, Rex JH. In vitro antifungal susceptibilities of Trichosporon species. Antimicrob Agents Chemother 2002;46:1144-6. 2. Yang R, Ao J, Wang W, Song K, Li R, Wang D. Disseminated trichosporonosis in China. Mycoses 2003;46:519-23. 3. Ebright JR, Fairfax MR, Vazquez JA. Trichosporon asahii, a nonCandida yeast that caused fatal septic shock in a patient without cancer or neutropenia. Clin Infect Dis 2001;33:e28-30. 4. Pulvirenti N, Dall’Oglio F, Greco AM, Oliveri S, Schwartz RA, Micali G. Superficial cutaneous Trichosporon asahii infection in an immunocompetent host. Int J Dermatol 2006;45: 1428-31. 5. Yun SJ, Lee JB, Shin MG, Kim SJ, Won YH, Lee SC. Cutaneous abscess by Trichosporon asahii developing on a steroid injection site in a healthy adult. Clin Dermatol 2005;31:545-7. doi:10.1016/j.jaad.2007.08.017
Treatment of nephrogenic systemic fibrosis with Re-PUVA To the Editor: Nephrogenic systemic fibrosis (NSF) is a rare fibrosing systemic disease, first recognized in 20001 that affects patients with renal insufficiency or renal failure. No single therapeutic regimen has been universally successful in treating this progressive fibrotic disease. We report significant clinical
Fig 1. Case 1. Patient with maximal flexion of digits before therapy (A) and 11 months after initiating therapy (B).
improvement in two cases of NSF with psoralens plus ultraviolet A (PUVA) plus retinoid treatment. Case 1. A 49-year-old male patient with NSF and receiving hemodialysis in whom conservative treatment had failed was started on a PUVA and retinoid (Re-PUVA) regimen. After 15 PUVA treatments (16.0 J/6:40 min/133 total J) and 11 weeks of acitretin (12.5 mg), the patient began noticing softening of the involved skin, a greater ability to clench his fist, and increased joint mobility with an approximate 60% improvement over baseline (Fig 1). He improved considerably after receiving a new kidney; however, after subsequent graft rejection, his disease returned. Within 2 months PUVA and acitretin therapy was restarted, and the patient again experienced softening of plaques. He has received a total of 123 PUVA treatments, receiving a total of 1756 J, and has maintained benefit and functionality.
S40 Letters
J AM ACAD DERMATOL AUGUST 2008
We recognize there has been a previous unsuccessful report of a patient who started retinoid-PUVA therapy, but treatments were stopped after 1 month because of muscle pain and lack of dermatologic improvement.5 Our first patient did not improve until week 5 of combined Re-PUVA treatment and our second patient did not have significant improvement until at least 4 weeks of combined therapy. With the dismal prognosis of this progressive disease and the dramatic clinical response of our two patients, we believe Re-PUVA therapy might be a viable, relatively safe, treatment option to improve functionality and quality of life in these patients. Keith L. Duffy, MD, Layne Green, MD, Ronald Harris, MD, MBA, and Douglas Powell, MD Department of Dermatology, University of Utah, Salt Lake City Funding sources: None. Conflicts of interest: None declared. Fig 2. Case 2. Medial aspect of left thigh before treatment (A) and after 6 months of combined therapy (B).
Reprint request: Douglas Powell, MD, University of Utah, Department of Dermatology, 30 N 1900 E, School of Medicine 4B454, Salt Lake City, UT 84132
Case 2. A 54-year-old female hemodialysis patient with NSF/nephrogenic fibrosing dermopathy had progressive disease after 2 months of physical therapy and was started on a regimen of acitretin (10 mg every other day) and PUVA. Initial improvement was noted after 10 PUVA treatments (9.0 J/3:45 min/38.5 total J); over the following 2 months the mobility in her left knee improved substantially with impressive softening of the plaques maximized after approximately 6 months (Fig 2). After 12 months of combined therapy consisting of 70 PUVA treatments, totaling 1202 J, she continues to have small but clinically significant alleviation of her disease. Comment. Recent reports suggest that gadolinium may be the etiologic agent that triggers the fibrotic cascade in NSF.2,3 Retrospectively we were able to confirm gadolinium exposure, specifically to gadodiamide (Omniscan, GE Healthcare, Princeton, NJ), in both patients. Exposure to clinical disease was approximately 4 months in our first patient and 2 weeks in our second patient. Brenner et al,4 in a review of PUVA in fibrosing skin disease, showed clearly there is proven benefit in morphea and scleroderma and questionable benefit in scleromyxedema. The mechanism of how exactly PUVA therapy is successful in treating sclerotic skin diseases has not been fully elucidated, but it is thought that PUVA acts either by inhibiting procollagen synthesis or by reducing the amount of transforming growth factor b-1.
E-mail: [email protected] REFERENCES 1. Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE. Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 2000;365:1000-1. 2. Grobner T. Gadolinium—a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 2006;21:1104-8. 3. USFDA Healthcare professional sheet — Gadolinium-containing contrast agents for Magnetic Resonance Imaging (MRI) FDA alert 06/2006. Development of serious and sometimes fatal nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy. Available at: www.fda.gov/cder/drugInfoSheets/HCP/gccaHCP.htm. 4. Brenner M, Herzinger T, Berking C, Plewig G, Degitz K. Phototherapy and photochemotherapy of sclerosing skin diseases. Photodermatol Photoimmunol Photomed 2005;21:157-65. 5. Lauchli S, Zortea-Caflisch C, Nestle FO, Burg G, Kempf W. Nephrogenic fibrosing dermopathy treated with extracorporeal photopheresis. Dermatology 2004;208:278-80. doi:10.1016/j.jaad.2007.08.035
Common variable immunodeficiency presenting as chronic urticaria To the Editor: A 15-year-old white boy presented with a 4-month history of daily pruritic hives, affecting his hands, feet, and legs. Medical history was significant for occasional repeated ear and sinus infections since age 8. Combined antihistamines provided minimal clinical response. A skin biopsy specimen demonstrated mild papillary dermal