OJBD  Vol.3 No.3 , September 2013
Cutaneous Manifestations of Sickle Cell Disease
Abstract: Sickle cell disease is an inherited erythrocyte disorder affecting multiple organ systems. As individuals are living well into middle age due to advances in diagnosis and treatment, further disease-related complications are being recognized. This article reviews the cutaneous manifestations of sickle cell disease including leg ulcers and acquired pseudoxanthoma elasticum.
Cite this paper: H. Jones, M. Blinder and M. Anadkat, "Cutaneous Manifestations of Sickle Cell Disease," Open Journal of Blood Diseases, Vol. 3 No. 3, 2013, pp. 94-99. doi: 10.4236/ojbd.2013.33019.

[1]   O. Brawley, L. Cornelius, L. Edwards, V. Gamble, B. Green, C. Inturrisi, et al., “NIH Conference Annals of Internal Medicine National Institutes of Health Consensus Development Conference Statement: Hydroxyurea Treatment for Sickle Cell Disease,” Annals of Internal Medicine, Vol. 148, No. 12, 2008, pp. 932-938. doi:10.7326/0003-4819-148-12-200806170-00220

[2]   M. Bender and W. Hobbs, “Gene Reveiws,” University of Washington, Seattle, 1993.

[3]   J. Herrick, “Peculiar Elongated and Sickle-shaped Red Blood Corpuscles in a Case of Severe Anemia. 1910,” Yale Journal of Biology and Medicine, Vol. 74, No. 3, 2001, pp. 179-184.

[4]   C. Cummer and C. LaRocco, “Ulcers of the Legs in Sickle Cell Anemia,” Archives of Dermatology, Vol. 42, No. 6, 1940, pp. 1015-1039. doi:10.1001/archderm.1940.01490180024002

[5]   V. Nolan, A. Adewoye, C. Baldwin, L. Wang, D. Wyszzynski, J. Farrell, et al., “Sickle Cell Leg Ulcers: Associations with Haemolysis and SNPs in Klotho, TEK and Genes of the TGF-B/BMP Pathway,” British Journal of Haematology, Vol. 133, No. 5, 2006, pp. 570-578. doi:10.1111/j.1365-2141.2006.06074.x

[6]   J. Trent and R. Kirsner, “Leg Ulcers in Sickle Cell Disease,” Advances in Skin & Wound Care, Vol. 17, No. 8, pp. 410-416. doi:10.1097/00129334-200410000-00010

[7]   F. Wolfort and T. Krizek, “Skin Ulceration in Sickle Cell Anemia,” Plastic and Reconstructive Surgery, Vol. 43, No. 1, 1969, pp. 71-77. doi:10.1097/00006534-196901000-00011

[8]   E. Chirico and V. Pialoux, “Role of Oxidative Stress in the Pathogenesis of Sickle Cell Disease,” IUBMB Life, Vol. 64, No. 1, 2012, pp. 72-80. doi:10.1002/iub.584

[9]   K. Wood, L. Hsu and M. Gladwin, “Sickle Cell Disease Vasculopathy: A State of Nitric Oxide Resistance,” Free Radical Biology & Medicine, Vol. 44, No. 8, 2008, pp. 1506-1528. doi:10.1016/j.freeradbiomed.2008.01.008

[10]   M. Koshy, R. Entsuah, A. Koranda, A. Kraus, R. Johnson, R. Bellvue, et al., “Leg Ulcers in Patients with Sickle Cell Disease,” Blood, Vol. 74, No. 4, 1989, pp. 1403-1408.

[11]   M. Halabi-Tawil, F. Lionnet, R. Girot, C. Bachmeyer, P. Lévy and S. Aractingi, “Sickle Cell Leg Ulcers: A Frequently Disabling Complication and a Marker of Severity,” British Journal of Dermatology, Vol. 158, No. 2, 2008, pp. 339-344. doi:10.1111/j.1365-2133.2007.08323.x

[12]   G. Serjeant, “Leg Ulceration in Sickle Cell Anemia,” Archives of Internal Medicine, Vol. 133, No. 4, 1974, pp. 690-694. doi:10.1001/archinte.1974.00320160184017

[13]   J. Eckman, “Leg Ulcers in Sickle Cell Disease,” Hematology/Oncology Clinics of North America, Vol. 10, No. 6, 1996, pp. 1333-1344. doi:10.1016/S0889-8588(05)70404-4

[14]   G. Serjeant, B. Serjeant, J. Mohan and A. Clare, “Leg Ulceration in Sickle Cell Disease: Medieval Medicine in a Modern World,” Hematology/Oncology Clinics of North America, Vol. 19, No. 5, 2005, pp. 943-956. doi:10.1016/j.hoc.2005.08.005

[15]   S. Robinson and S. Tasker, “Chronic Leg Ulcers of Sickle Cell Anemia; Report of Case; with Reference to Recognition,” California Western Journal of Medicine, Vol. 64, No. 4, 1946, pp. 250-2.

[16]   S. Sehgal and B. Arunkumar, “Microbial Flora and Its Significance in Pathology of Sickle Cell Disease Leg Ulcers,” Infection, Vol. 20, No. 2, 1992, pp. 86-88. doi:10.1007/BF01711070

[17]   L. McMahon, H. Tamary, M. Askin, P. Adams-Graves, R. Eberhardt, M. Sutton, et al., “A Randomized Phase II Trial of Arginine Butyrate with Standard Local Therapy in Refractory Sickle Cell Leg Ulcers,” British Journal of Haematology, Vol. 15, No. 5, 2010, pp. 516-524. doi:10.1111/j.1365-2141.2010.08395.x

[18]   G. Serjeant, R. Galloway and M. Gueri, “Oral Zinc Sulphate in Sickle-Cell Ulcers,” Lancet, Vol. 31, No. 2, 1970, pp. 891-892. doi:10.1016/S0140-6736(70)92067-2

[19]   R. Ware and B. Aygun. Advances in the Use of Hydroxyurea,” Hematology ASH Education Program, Vol. 2009, No. 1, 2009, pp. 62-69. doi:10.1182/asheducation-2009.1.62

[20]   O. Platt, “Hydroxyurea for the Treatment of Sickle Cell Anemia,” The New England Journal of Medicine, Vol. 358, No. 13, 2008, pp. 1362-1369. doi:10.1056/NEJMct0708272

[21]   M. Gladwin, J. Shelhamer, F. Ognibene, M. Pease-Fye, J. Nichols, B. Link, et al., “Nitric Oxide Donor Properties of Hydroxyurea in Patients with Sickle Cell Disease,” British Journal of Haematology, Vol. 116, No. 2, 2002, pp. 436-444. doi:10.1046/j.1365-2141.2002.03274.x

[22]   R. Khouri and J. Upton, “Bilateral Lower Limb Salvage with Free Flaps in a Patient with Sickle Cell Ulcers,” Annals of Plastic Surgery, Vol. 27, No. 6, 1991, pp. 574-576. doi:10.1097/00000637-199112000-00011

[23]   R. Richards, C. Bowen and M. Glynn. Microsurgical Free Flap Transfer in Sickle Cell Disease,” Annals of Plastic Surgery, Vol. 29, No. 3, 1992, pp. 278-281. doi:10.1097/00000637-199112000-00011

[24]   M. Gueri and G. Serjeant, “Leg Ulcers in Sickle-Cell Anaemia,” Tropical and Geographical Medicine, Vol. 22, No. 2, 1970, pp. 155-160.

[25]   J. Uitto, L. Bervcovitch, S. Terry and P. Terry, “Pseudoxanthoma Elasticum: Progress in Diagnostics and Research towards Treatment: Summary of the 2010 PXE International Research Meeting,” American Journal of Medical Genetics Part A, Vol. 155A, No. 7, 2011, pp. 1517-1526. doi:10.1002/ajmg.a.34067

[26]   W. Geeraets and D. Guerry, “Angioid Streaks and Sickle Cell Disease,” American Journal of Ophthalmology, Vol. 49, 1960, pp. 450-470.

[27]   K. Suerig and F. Siefert, “Pseudoxanthoma Elasticum and Sickle Cell Anemia,” Archives of Internal Medicine, Vol. 113, No. 1, 1964, pp. 135-141. doi:10.1001/archinte.1964.00280070137022

[28]   E. Fabbri, G. Forni, G. Guerrini and C. Borgna-Pignatti, “Pseudoxanthoma-Elasticum-Like Syndrome and Thalassemia: An Update,” Dermatology Online Journal, Vol. 15, No. 7, 2009, p. 7.

[29]   A. Aessopos, P. Savvides, G. Stamatelos, I. Rombos, T. Tassiopoulos, M. Karagiorga, et al., “Pseudoxanthoma Elasticum-Like Skin Lesions and Angioid Streaks in Beta Thalassemia,” American Journal of Hematology, Vol. 41, No. 3, 1992, pp. 159-164. doi:10.1002/ajh.2830410304

[30]   Q. Jiang, M. Endo, F. Dibra, K. Wang and J. Uitto, “Pseudoxanthoma Elasticum Is a Metabolic Disease,” Journal of Investigative Dermatology, Vol. 129, No. 2, 2009, pp. 348-354. doi:10.1038/jid.2008.212

[31]   A. Aessopos, D. Farmakis and D. Loukopoulos, “Elastic Tissue Abnormalities Resembling Pseudoxanthoma Elas- ticum in Beta Thalassemia and the Sickling Syndromes,” Blood, Vol. 99, No. 1, 2002, pp. 30-35. doi:10.1182/blood.V99.1.30

[32]   T. van Meurs, J. van Hagen, M. van de Scheur, H. Vermaat, M. Ruijs, H. van den Hoogenband, et al., “Classic Pseudoxanthoma Elasticum in a Patient with Sickle Cell Disease,” Journal of the American Academy of Dermatology, Vol. 56, No. 1, 2007, pp. 170-171. doi:10.1016/j.jaad.2006.10.023

[33]   A. Adam and M. Maritim, “Pseudoxanthoma Elasticum in a Patient with Sickle Cell Disease: Case Report,” East African Medical Journal, Vol. 85, No. 2, 2008, pp. 98-101. doi:10.4314/eamj.v85i2.9613

[34]   Q. Li, Q. Jiang, E. Pfendner, A. Váradi and J. Uitto, “Pseudoxanthoma Elasticum: Clinical Phenotypes, Molecular Genetics and Putative Pathomechanisms,” Experimental Dermatology, Vol. 18, No. 1, 2009, pp. 1-11. doi:10.1111/j.1600-0625.2008.00795.x

[35]   I. Georgalas, I. Tservakis, D. Papaconstaninou, M. Kardara, C. Koutsandrea and I. Ladas, “Pseudoxanthoma Elasticum, Ocular Manifestations, Complications and Treatment,” Clinical and Experimental Optometry, Vol. 94, No. 2, 2011, pp. 169-80. doi:10.1111/j.1444-0938.2010.00559.x

[36]   E. Cacciola, R. Musso, R. Giustolisi, E. Cacciola and M. Alessi, “Blood Hypercoagulability as a Risk Factor for Leg Ulcers in Sickle Cell Disease,” Blood, Vol. 75, No. 12, 1990, pp. 2467-2478.