Original Article Submitted: 29.8.2014 Accepted: 4.9.2014 Conflict of interest None.
DOI: 10.1111/ddg.12520
Early treatment with rutoside and ascorbic acid is highly effective for progressive pigmented purpuric dermatosis
Sarah M. Schober 1, Wiebke K. Peitsch1, Gisela Bonsmann2, Dieter Metze2, Kai Thomas2, Tobias Goerge2, Thomas A. Luger2, Stefan W. Schneider 1 (1) Department of Dermatology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany (2) Department of Dermatology, University of Münster, Münster, Germany
Summary Background and Objectives: Progressive pigmented purpuric dermatosis (PPPD, Schamberg disease) is a rare benign, but chronic dermatosis frequently misdiagnosed as vasculitis or bleeding disorder. Although affected patients experience significant impairment in quality of life no effective treatment has been established. The aim of our two center case series was to evaluate efficacy and tolerability of the antioxidants rutoside and ascorbic acid as combination treatment for PPPD. Patients and Methods: A retrospective review was performed on 35 patients with PPPD treated with 2 × 50 mg rutoside and 1 000 mg ascorbic acid daily between 2004 until 2011. The mean treatment duration was 8.2 months. Results: 71.4 % of the participants experienced complete clearance and 20.0 % an improvement of more than 50 %, accompanied by increased quality of life. Nine participants (25.1 %) relapsed after discontinuation. In seven, rutoside and ascorbic acid was re-initiated, and all responded again. Only three participants reported mild adverse effects. Participants with shorter disease duration showed better therapeutic success, shorter time to response and lower risk of recurrence. Conclusion: Oral rutoside and ascorbic acid may be an efficient and well tolerated treatment for PPPD. Early treatment is recommended to achieve best clinical outcome.
Introduction Pigmented purpuric eruptions are chronic and relapsing dermatoses characterized by petechiae, pigmentary macules and red-brown pigmentation typically distributed symmetrically on the lower limbs [1–3]. The most common type is progressive pigmented purpuric dermatosis (PPPD), first described in 1901 by Jay Frank Schamberg [3]. PPPD is mostly asymptomatic except for mild pruritus [1], but patients are often disturbed by its appearance. Physicians who are unaware of the diagnosis worry about an underlying disease and initiate extensive diagnostics to exclude vasculitis, coagulopathy or
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associated hematologic malignancy. A simple clinical test, the Rumpel-Leede test (RLT) demonstrating capillary fragility which is usually positive in patients with PPPD, may be helpful for differential diagnosis [4]. The pathogenesis of PPPD has not yet been fully clarified, but according to three different hypotheses, capillary fragility, humoral immunity and cellular immunity may play an essential role [5]. Many potential triggers and amplification factors have been suggested, including venous hypertension, exercise, focal infections, drugs, contact allergy to clothing dyes, and chemicals [1, 6]. Nevertheless, in most cases the etiology is unknown.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1212
Original Article Rutoside and ascorbic acid for PPPD
Although many different attempts have been made to treat PPPD, no established treatment exists that has been proven effective in the majority of patients. Since the disease is thought to be due to or aggravated by increased capillary fragility, treatment has been attempted with antioxidants, including the combination of rutoside and ascorbic acid, and there are anecdotic case reports about their efficiency in PPPD [7, 8]. However, there is no formal proof of these findings so far. Therefore, we conducted a retrospective two center study evaluating the efficiency and tolerability of rutoside and ascorbic acid in 35 patients with PPPD treated with this combination between 2004 and 2011.
new potential treatment of PPPD all patients were evaluated by two dermatologists and extensive hematologic testing was performed to exclude other purpura-associated diseases, most importantly platelet function disorders. To identify congenital or acquired bleeding disorders patients were asked about mucocutaneous bleeding, recurrent nosebleeds, menorrhagia or metrorrhagia (women), postsurgical bleeding and easy bruising and bleeding. In addition an initial laboratory screening test was performed, including quantification of platelets, prothrombin time, activated partial thromboplastin time, and a complete blood count.
Study design
Material and methods Participants All patients with PPPD who were treated with rutoside and ascorbic acid at the Departments of Dermatology of the University Medical Center Mannheim, Heidelberg University, and of the University of Münster, Germany, between 01 August 2004 and 27 February 2011 were included in this retrospective analysis (n = 35, 30 from Münster and 5 from Mannheim). Inclusion criteria were diagnosis of PPPD, either based on clinical findings together with positive RLT on unaffected skin, or based on clinical findings and confirmed by histopathology. When the diagnosis of PPPD was unambiguously established by two independent, experienced dermatologists (SWS, WL, GB, TG) based on typical clinical findings and lack of abnormal laboratory parameters, we occasionally abstained from histological proof. Other inclusion criteria were treatment with rutoside and ascorbic acid for at least four weeks, and a minimum follow-up of three months. Exclusion criteria were liver, kidney or myeloproliferative disease, vasculitis, active malignancy (except basal cell carcinoma), hemophilia, coagulopathies, drug-induced thrombocytopenia, disorders of platelet function or severe infections as possible causes for purpura. At the Department of Dermatology of the University of Münster, patients with PPPD had been screened systematically since August 2004. Out of 59 patients treated with rutoside and ascorbic acid, 30 fulfilled all study criteria and were included in our analysis. In Mannheim, patients with PPPD had been systematically recorded since January 2008. Out of 17 patients treated with rutoside and ascorbic acid, 5 fulfilled all study criteria and were included. So the total number of 76 patients had to be reduced to 35 due to refusal to participate, insufficient compliance and invalid diagnosis. This study was conducted as an initial study to evaluate parameters for a planned prospective study. In view of a
All patients were examined at least two times by one of the authors upon treatment with rutoside and ascorbic acid. Data was collected by retrospective review of patient records, microfilms and photographs and by interviews with the participants. The following Information was extracted from medical records: sex, age, possible triggers and amplification factors of the PPPD, duration and efficiency of previous treatments, comorbidities, comedication, results of RLT and histological examination, laboratory findings, localization, duration and course of the PPPD, dosage of rutoside and ascorbic acid (standard dose: 50 mg rutoside BID and 1 000 mg ascorbic acid QD), duration, time to response, efficiency and adverse events, concomitant treatments and relapses after discontinuation. Interviews were conducted between March and July 2011 with 33 participants by one of the investigators (SMS). The standardized questionnaire used for the interviews included 33 questions focusing on disease burden before and after treatment with rutoside and ascorbic acid, course after discontinuation, and satisfaction with treatment. Treatment satisfaction was assessed on a five-point scale, comprising the categories “very satisfied”, “rather satisfied”, “undecided”, “rather dissatisfied” and “very dissatisfied”. Standard treatment consisted of 2 × 50 mg rutoside and 1 000 mg ascorbic acid per day. Four patients (including 3 children) received only 50 mg rutoside per day, two participants only 500 mg ascorbic acid daily. In six participants (17.1 %) the dosage of rutoside was increased to 150 mg daily, in one participant to a mean dosage of 163 mg rutoside per day. Treatment outcome was classified into four levels. L evel 1 was defined as complete clearance of the skin lesions, indicating restitutio ad integrum. Level 2 reflected improvement of more than 50 %, i.e., clearance of more than 50 % of the lesions documented before initiation of treatment. L evel 3 corresponded to improvement of less than 50 % (defined as clearance of less than 50 % of the initial lesions) and level 4 indicated lack of response. In addition professional skin images of affected skin areas were analyzed by two
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1212
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Original Article Rutoside and ascorbic acid for PPPD
independent dermatologists (pre- and post-treatment). To avoid overestimation of the therapeutic efficacy, only level 1 and level 2 responses were used to calculate the response rate. Reduction of itch, improvement of cosmetic appearance, adverse effects and treatment costs were assumed to be the main determinants of the reported patient satisfaction. Study procedures were approved by the Ethic Committee of the Medical Faculty Mannheim, University of Heidelberg and performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from each adult patient and from both parents (and legal guardians) of children 90 %), our study opens a promising perspective for a novel first-line treatment of a so far extremely refractory condition.
Financial support This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB/TR23 subprojects A9 to S.W. Schneider) and DFG “SHENC” (SCHN 474/5-1 to S.W. Schneider) and GO 1360/4-1 to Tobias Goerge.
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Correspondence to Prof. Dr. med. Stefan W. Schneider Department of Dermatology University Medical Center Mannheim Heidelberg University Theodor-Kutzer-Ufer 1-3 68167 Mannheim, Germany E-mail: [email protected]
References 1
Sardana K, Sarkar R, Sehgal VN. Pigmented purpuric dermatoses: an overview. Int J Dermatol 2004; 43: 482–8. 2 Schamberg J. A peculiar progressive pigmentary disease of the skin. Br J Dermatol 1901; 13. 3 Schamberg J. Report of three cases of progressive pigmentary dermatoses with particular reference to the blood cholesterol. Br J Dermatol 1927; 39: 389–93. 4 Sherertz EF. Pigmented purpuric eruptions. Semin Thromb Hemost 1984; 10: 190–5. 5 Schroeder-Devere T. Pigmented Purpuric Dermatoses. In: Fitzpatrick TB: Fitzpatrick’s Dermatoloy in General Medicine. 7 ed. New York: McGraw-Hill, 2008: 1633–36. 6 Tristani-Firouzi P, Meadows KP, Vanderhooft S. Pigmented purpuric eruptions of childhood: a series of cases and review of literature. Pediatr Dermatol 2001; 18: 299–304. 7 Laufer F. The treatment of progressive pigmented purpura with ascorbic acid and a bioflavonoid rutoside. J Drugs Dermatol 2006; 5: 290–3. 8 Reinhold U, Seiter S, Ugurel S, Tilgen W. Treatment of progressive pigmented purpura with oral bioflavonoids and ascorbic acid: an open pilot study in 3 patients. J Am Acad Dermatol 1999; 41: 207–8. 9 Champion RH, Down PM. Purpura. In: Rook A, Wilkinson DS, Ebling FG: Textbook of Dermatology. 6 ed. Oxford, London, Edinburgh, Malden, Carlton, Delavigne, Paris: Blackwell Science, 1998: 2141–54. 10 Draelos ZK, Hansen RC. Schamberg’s purpura in children: case study and literature review. Clin Pediatr (Phila) 1987; 26: 659–61. 11 Newton RC, Raimer SS. Pigmented purpuric eruptions. Dermatol Clin 1985; 3: 165–9. 12 Gandhi V, Singal A, Sachdeva B, Bhattacharya SN. Treatment of Schamberg’s disease with pentoxifylline-therapeutic trial. Indian J Dermatol Venereol Leprol 2003; 69: 25–6. 13 Panda S, Malakar S, Lahiri K. Oral pentoxifylline vs topical betamethasone in Schamberg disease: a comparative randomized investigator-blinded parallel-group trial. Arch Dermatol 2004; 140: 491–3. 14 Kumrah L, George R, George S. An open trial of pentoxifylline in schamberg’s disease. Indian J Dermatol Venereol Leprol 2000; 66: 73–5. 15 Fathy H, Abdelgaber S. Treatment of pigmented purpuric dermatoses with narrow-band UVB: a report of six cases. J Eur Acad Dermatol Venereol 2011; 25: 603–6. 16 Milea M, Dimov HA, Cribier B. Generalized Schamberg’s disease treated with PUVA in a child. Ann Dermatol Venereol 2007; 134: 378–80.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1212
Original Article Rutoside and ascorbic acid for PPPD
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Wong WK, Ratnam KV. A report of two cases of pigmented purpuric dermatoses treated with PUVA therapy. Acta Derm Venereol 1991; 71: 68–70. Seckin D, Yazici Z, Senol A, Demircay Z. A case of Schamberg’s disease responding dramatically to PUVA treatment. Photodermatol Photoimmunol Photomed 2008; 24: 95–6. Bohm M, Bonsmann G, Luger TA. Resolution of lichen aureus in a 10-year-old child after topical pimecrolimus. Br J Dermatol 2004; 151: 519–20. Agrawal SK, Gandhi V, Bhattacharya SN. Calcium dobesilate (Cd) in pigmented purpuric dermatosis (PPD): a pilot evaluation. J Dermatol 2004; 31: 98–103. deGodoy JM, Batigalia F. Aminaphtone in the control of Schamberg’s disease. Thromb J 2009; 7: 8. Tamaki K, Yasaka N, Osada A et al. Successful treatment of pigmented purpuric dermatosis with griseofulvin. Br J Dermatol 1995; 132: 159–60. Geller M. Benefit of colchicine in the treatment of Schamberg’s disease. Ann Allergy Asthma Immunol 2000; 85: 246. Kim SK, Kim EH, Kim YC. Treatment of pigmented purpuric dermatosis with topical photodynamic therapy. Dermatology 2009; 219: 184–6. D’Ambrosia RA, Rajpara VS, Glogau RG. The successful treatment of Schamberg’s disease with the 595 nm vascular laser. Dermatol Surg 2011; 37: 100–1. Okada K, Ishikawa O, Miyachi Y. Purpura pigmentosa chronica successfully treated with oral cyclosporin A. Br J Dermatol 1996; 134: 180–1. Hoesly FJ, Huerter CJ, Shehan JM. Purpura annularis telangiectodes of Majocchi: case report and review of the literature. Int J Dermatol 2009; 48: 1129–33.
28 Frei B. Reactive oxygen species and antioxidant vitamins: mechanisms of action. Am J Med 1994; 97: 5–13; discussion 22-8. 29 Utoguchi N, Ikeda K, Saeki K et al. Ascorbic acid stimulates barrier function of cultured endothelial cell monolayer. J Cell Physiol 1995; 163: 393–9. 30 Halliwell B. The role of oxygen radicals in human disease, with particular reference to the vascular system. Haemostasis 1993; 23(Suppl 1): 118–26. 31 Havsteen B. Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol 1983; 32: 1141–8. 32 Chen YT, Zheng RL, Jia ZJ, Ju Y. Flavonoids as superoxide scavengers and antioxidants. Free Radic Biol Med 1990; 9: 19–21. 33 Wiejak J, Dunlop J, Mackay SP, Yarwood SJ. Flavanoids induce expression of the suppressor of cytokine signalling 3 (SOCS3) gene and suppress IL-6-activated signal transducer and activator of transcription 3 (STAT3) activation in vascular endothelial cells. Biochem J 2013; 454: 283–93. 34 Wadworth AN, Faulds D. Hydroxyethylrutosides. A review of its pharmacology, and therapeutic efficacy in venous insufficiency and related disorders. Drugs 1992; 44: 1013–32. 35 Mandl J, Szarka A, Banhegyi G. Vitamin C: update on physiology and pharmacology. Br J Pharmacol 2009; 157: 1097–110. 36 Peterkofsky B. Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. Am J Clin Nutr 1991; 54: 1135–40. 37 Nachman RL, Rafii S. Platelets, petechiae, and preservation of the vascular wall. N Engl J Med 2008; 359: 1261–70. 38 Ratnam KV, Su WP, Peters MS. Purpura simplex (inflammatory purpura without vasculitis): a clinicopathologic study of 174 cases. J Am Acad Dermatol 1991; 25: 642–7.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1212
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DOI: 10.1111/ddg.12520
Early treatment with rutoside and ascorbic acid is highly effective for progressive pigmented purpuric dermatosis
Sarah M. Schober 1, Wiebke K. Peitsch1, Gisela Bonsmann2, Dieter Metze2, Kai Thomas2, Tobias Goerge2, Thomas A. Luger2, Stefan W. Schneider 1 (1) Department of Dermatology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany (2) Department of Dermatology, University of Münster, Münster, Germany
Summary Background and Objectives: Progressive pigmented purpuric dermatosis (PPPD, Schamberg disease) is a rare benign, but chronic dermatosis frequently misdiagnosed as vasculitis or bleeding disorder. Although affected patients experience significant impairment in quality of life no effective treatment has been established. The aim of our two center case series was to evaluate efficacy and tolerability of the antioxidants rutoside and ascorbic acid as combination treatment for PPPD. Patients and Methods: A retrospective review was performed on 35 patients with PPPD treated with 2 × 50 mg rutoside and 1 000 mg ascorbic acid daily between 2004 until 2011. The mean treatment duration was 8.2 months. Results: 71.4 % of the participants experienced complete clearance and 20.0 % an improvement of more than 50 %, accompanied by increased quality of life. Nine participants (25.1 %) relapsed after discontinuation. In seven, rutoside and ascorbic acid was re-initiated, and all responded again. Only three participants reported mild adverse effects. Participants with shorter disease duration showed better therapeutic success, shorter time to response and lower risk of recurrence. Conclusion: Oral rutoside and ascorbic acid may be an efficient and well tolerated treatment for PPPD. Early treatment is recommended to achieve best clinical outcome.
Introduction Pigmented purpuric eruptions are chronic and relapsing dermatoses characterized by petechiae, pigmentary macules and red-brown pigmentation typically distributed symmetrically on the lower limbs [1–3]. The most common type is progressive pigmented purpuric dermatosis (PPPD), first described in 1901 by Jay Frank Schamberg [3]. PPPD is mostly asymptomatic except for mild pruritus [1], but patients are often disturbed by its appearance. Physicians who are unaware of the diagnosis worry about an underlying disease and initiate extensive diagnostics to exclude vasculitis, coagulopathy or
1112
associated hematologic malignancy. A simple clinical test, the Rumpel-Leede test (RLT) demonstrating capillary fragility which is usually positive in patients with PPPD, may be helpful for differential diagnosis [4]. The pathogenesis of PPPD has not yet been fully clarified, but according to three different hypotheses, capillary fragility, humoral immunity and cellular immunity may play an essential role [5]. Many potential triggers and amplification factors have been suggested, including venous hypertension, exercise, focal infections, drugs, contact allergy to clothing dyes, and chemicals [1, 6]. Nevertheless, in most cases the etiology is unknown.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1212
Original Article Rutoside and ascorbic acid for PPPD
Although many different attempts have been made to treat PPPD, no established treatment exists that has been proven effective in the majority of patients. Since the disease is thought to be due to or aggravated by increased capillary fragility, treatment has been attempted with antioxidants, including the combination of rutoside and ascorbic acid, and there are anecdotic case reports about their efficiency in PPPD [7, 8]. However, there is no formal proof of these findings so far. Therefore, we conducted a retrospective two center study evaluating the efficiency and tolerability of rutoside and ascorbic acid in 35 patients with PPPD treated with this combination between 2004 and 2011.
new potential treatment of PPPD all patients were evaluated by two dermatologists and extensive hematologic testing was performed to exclude other purpura-associated diseases, most importantly platelet function disorders. To identify congenital or acquired bleeding disorders patients were asked about mucocutaneous bleeding, recurrent nosebleeds, menorrhagia or metrorrhagia (women), postsurgical bleeding and easy bruising and bleeding. In addition an initial laboratory screening test was performed, including quantification of platelets, prothrombin time, activated partial thromboplastin time, and a complete blood count.
Study design
Material and methods Participants All patients with PPPD who were treated with rutoside and ascorbic acid at the Departments of Dermatology of the University Medical Center Mannheim, Heidelberg University, and of the University of Münster, Germany, between 01 August 2004 and 27 February 2011 were included in this retrospective analysis (n = 35, 30 from Münster and 5 from Mannheim). Inclusion criteria were diagnosis of PPPD, either based on clinical findings together with positive RLT on unaffected skin, or based on clinical findings and confirmed by histopathology. When the diagnosis of PPPD was unambiguously established by two independent, experienced dermatologists (SWS, WL, GB, TG) based on typical clinical findings and lack of abnormal laboratory parameters, we occasionally abstained from histological proof. Other inclusion criteria were treatment with rutoside and ascorbic acid for at least four weeks, and a minimum follow-up of three months. Exclusion criteria were liver, kidney or myeloproliferative disease, vasculitis, active malignancy (except basal cell carcinoma), hemophilia, coagulopathies, drug-induced thrombocytopenia, disorders of platelet function or severe infections as possible causes for purpura. At the Department of Dermatology of the University of Münster, patients with PPPD had been screened systematically since August 2004. Out of 59 patients treated with rutoside and ascorbic acid, 30 fulfilled all study criteria and were included in our analysis. In Mannheim, patients with PPPD had been systematically recorded since January 2008. Out of 17 patients treated with rutoside and ascorbic acid, 5 fulfilled all study criteria and were included. So the total number of 76 patients had to be reduced to 35 due to refusal to participate, insufficient compliance and invalid diagnosis. This study was conducted as an initial study to evaluate parameters for a planned prospective study. In view of a
All patients were examined at least two times by one of the authors upon treatment with rutoside and ascorbic acid. Data was collected by retrospective review of patient records, microfilms and photographs and by interviews with the participants. The following Information was extracted from medical records: sex, age, possible triggers and amplification factors of the PPPD, duration and efficiency of previous treatments, comorbidities, comedication, results of RLT and histological examination, laboratory findings, localization, duration and course of the PPPD, dosage of rutoside and ascorbic acid (standard dose: 50 mg rutoside BID and 1 000 mg ascorbic acid QD), duration, time to response, efficiency and adverse events, concomitant treatments and relapses after discontinuation. Interviews were conducted between March and July 2011 with 33 participants by one of the investigators (SMS). The standardized questionnaire used for the interviews included 33 questions focusing on disease burden before and after treatment with rutoside and ascorbic acid, course after discontinuation, and satisfaction with treatment. Treatment satisfaction was assessed on a five-point scale, comprising the categories “very satisfied”, “rather satisfied”, “undecided”, “rather dissatisfied” and “very dissatisfied”. Standard treatment consisted of 2 × 50 mg rutoside and 1 000 mg ascorbic acid per day. Four patients (including 3 children) received only 50 mg rutoside per day, two participants only 500 mg ascorbic acid daily. In six participants (17.1 %) the dosage of rutoside was increased to 150 mg daily, in one participant to a mean dosage of 163 mg rutoside per day. Treatment outcome was classified into four levels. L evel 1 was defined as complete clearance of the skin lesions, indicating restitutio ad integrum. Level 2 reflected improvement of more than 50 %, i.e., clearance of more than 50 % of the lesions documented before initiation of treatment. L evel 3 corresponded to improvement of less than 50 % (defined as clearance of less than 50 % of the initial lesions) and level 4 indicated lack of response. In addition professional skin images of affected skin areas were analyzed by two
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1212
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Original Article Rutoside and ascorbic acid for PPPD
independent dermatologists (pre- and post-treatment). To avoid overestimation of the therapeutic efficacy, only level 1 and level 2 responses were used to calculate the response rate. Reduction of itch, improvement of cosmetic appearance, adverse effects and treatment costs were assumed to be the main determinants of the reported patient satisfaction. Study procedures were approved by the Ethic Committee of the Medical Faculty Mannheim, University of Heidelberg and performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from each adult patient and from both parents (and legal guardians) of children 90 %), our study opens a promising perspective for a novel first-line treatment of a so far extremely refractory condition.
Financial support This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB/TR23 subprojects A9 to S.W. Schneider) and DFG “SHENC” (SCHN 474/5-1 to S.W. Schneider) and GO 1360/4-1 to Tobias Goerge.
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Correspondence to Prof. Dr. med. Stefan W. Schneider Department of Dermatology University Medical Center Mannheim Heidelberg University Theodor-Kutzer-Ufer 1-3 68167 Mannheim, Germany E-mail: [email protected]
References 1
Sardana K, Sarkar R, Sehgal VN. Pigmented purpuric dermatoses: an overview. Int J Dermatol 2004; 43: 482–8. 2 Schamberg J. A peculiar progressive pigmentary disease of the skin. Br J Dermatol 1901; 13. 3 Schamberg J. Report of three cases of progressive pigmentary dermatoses with particular reference to the blood cholesterol. Br J Dermatol 1927; 39: 389–93. 4 Sherertz EF. Pigmented purpuric eruptions. Semin Thromb Hemost 1984; 10: 190–5. 5 Schroeder-Devere T. Pigmented Purpuric Dermatoses. In: Fitzpatrick TB: Fitzpatrick’s Dermatoloy in General Medicine. 7 ed. New York: McGraw-Hill, 2008: 1633–36. 6 Tristani-Firouzi P, Meadows KP, Vanderhooft S. Pigmented purpuric eruptions of childhood: a series of cases and review of literature. Pediatr Dermatol 2001; 18: 299–304. 7 Laufer F. The treatment of progressive pigmented purpura with ascorbic acid and a bioflavonoid rutoside. J Drugs Dermatol 2006; 5: 290–3. 8 Reinhold U, Seiter S, Ugurel S, Tilgen W. Treatment of progressive pigmented purpura with oral bioflavonoids and ascorbic acid: an open pilot study in 3 patients. J Am Acad Dermatol 1999; 41: 207–8. 9 Champion RH, Down PM. Purpura. In: Rook A, Wilkinson DS, Ebling FG: Textbook of Dermatology. 6 ed. Oxford, London, Edinburgh, Malden, Carlton, Delavigne, Paris: Blackwell Science, 1998: 2141–54. 10 Draelos ZK, Hansen RC. Schamberg’s purpura in children: case study and literature review. Clin Pediatr (Phila) 1987; 26: 659–61. 11 Newton RC, Raimer SS. Pigmented purpuric eruptions. Dermatol Clin 1985; 3: 165–9. 12 Gandhi V, Singal A, Sachdeva B, Bhattacharya SN. Treatment of Schamberg’s disease with pentoxifylline-therapeutic trial. Indian J Dermatol Venereol Leprol 2003; 69: 25–6. 13 Panda S, Malakar S, Lahiri K. Oral pentoxifylline vs topical betamethasone in Schamberg disease: a comparative randomized investigator-blinded parallel-group trial. Arch Dermatol 2004; 140: 491–3. 14 Kumrah L, George R, George S. An open trial of pentoxifylline in schamberg’s disease. Indian J Dermatol Venereol Leprol 2000; 66: 73–5. 15 Fathy H, Abdelgaber S. Treatment of pigmented purpuric dermatoses with narrow-band UVB: a report of six cases. J Eur Acad Dermatol Venereol 2011; 25: 603–6. 16 Milea M, Dimov HA, Cribier B. Generalized Schamberg’s disease treated with PUVA in a child. Ann Dermatol Venereol 2007; 134: 378–80.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1212
Original Article Rutoside and ascorbic acid for PPPD
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Wong WK, Ratnam KV. A report of two cases of pigmented purpuric dermatoses treated with PUVA therapy. Acta Derm Venereol 1991; 71: 68–70. Seckin D, Yazici Z, Senol A, Demircay Z. A case of Schamberg’s disease responding dramatically to PUVA treatment. Photodermatol Photoimmunol Photomed 2008; 24: 95–6. Bohm M, Bonsmann G, Luger TA. Resolution of lichen aureus in a 10-year-old child after topical pimecrolimus. Br J Dermatol 2004; 151: 519–20. Agrawal SK, Gandhi V, Bhattacharya SN. Calcium dobesilate (Cd) in pigmented purpuric dermatosis (PPD): a pilot evaluation. J Dermatol 2004; 31: 98–103. deGodoy JM, Batigalia F. Aminaphtone in the control of Schamberg’s disease. Thromb J 2009; 7: 8. Tamaki K, Yasaka N, Osada A et al. Successful treatment of pigmented purpuric dermatosis with griseofulvin. Br J Dermatol 1995; 132: 159–60. Geller M. Benefit of colchicine in the treatment of Schamberg’s disease. Ann Allergy Asthma Immunol 2000; 85: 246. Kim SK, Kim EH, Kim YC. Treatment of pigmented purpuric dermatosis with topical photodynamic therapy. Dermatology 2009; 219: 184–6. D’Ambrosia RA, Rajpara VS, Glogau RG. The successful treatment of Schamberg’s disease with the 595 nm vascular laser. Dermatol Surg 2011; 37: 100–1. Okada K, Ishikawa O, Miyachi Y. Purpura pigmentosa chronica successfully treated with oral cyclosporin A. Br J Dermatol 1996; 134: 180–1. Hoesly FJ, Huerter CJ, Shehan JM. Purpura annularis telangiectodes of Majocchi: case report and review of the literature. Int J Dermatol 2009; 48: 1129–33.
28 Frei B. Reactive oxygen species and antioxidant vitamins: mechanisms of action. Am J Med 1994; 97: 5–13; discussion 22-8. 29 Utoguchi N, Ikeda K, Saeki K et al. Ascorbic acid stimulates barrier function of cultured endothelial cell monolayer. J Cell Physiol 1995; 163: 393–9. 30 Halliwell B. The role of oxygen radicals in human disease, with particular reference to the vascular system. Haemostasis 1993; 23(Suppl 1): 118–26. 31 Havsteen B. Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol 1983; 32: 1141–8. 32 Chen YT, Zheng RL, Jia ZJ, Ju Y. Flavonoids as superoxide scavengers and antioxidants. Free Radic Biol Med 1990; 9: 19–21. 33 Wiejak J, Dunlop J, Mackay SP, Yarwood SJ. Flavanoids induce expression of the suppressor of cytokine signalling 3 (SOCS3) gene and suppress IL-6-activated signal transducer and activator of transcription 3 (STAT3) activation in vascular endothelial cells. Biochem J 2013; 454: 283–93. 34 Wadworth AN, Faulds D. Hydroxyethylrutosides. A review of its pharmacology, and therapeutic efficacy in venous insufficiency and related disorders. Drugs 1992; 44: 1013–32. 35 Mandl J, Szarka A, Banhegyi G. Vitamin C: update on physiology and pharmacology. Br J Pharmacol 2009; 157: 1097–110. 36 Peterkofsky B. Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. Am J Clin Nutr 1991; 54: 1135–40. 37 Nachman RL, Rafii S. Platelets, petechiae, and preservation of the vascular wall. N Engl J Med 2008; 359: 1261–70. 38 Ratnam KV, Su WP, Peters MS. Purpura simplex (inflammatory purpura without vasculitis): a clinicopathologic study of 174 cases. J Am Acad Dermatol 1991; 25: 642–7.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1212
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![[Progressive pigmented purpuric dermatosis in young children].](/assets/img/hold.png)
