Cutaneous Manifestation of Β‑Thalassemic Patients Mohamed A

[Downloaded free from http://www.mmj.eg.net on Thursday, January 14, 2021, IP: 156.204.184.20]

Original article 267

Cutaneous manifestation of β‑thalassemic patients Mohamed A. Gaber, Marwa Galal

Departement of Dermatology and Venereology, Objective Menoufia University, Menoufia, Egypt The aim was to study the prevalence of common dermatological problems in patients with Correspondence to Marwa Galal, MBBCh, β‑thalassemia major to help rapid treatment and prevent complications. Shiben Elkom, Menoufia, Background Egypt β‑Thalassemia major affects multiple organs and is associated with considerable morbidity Tel: +20 100 276 8385; Postal code: 32511; and mortality. In β‑thalassemia, a wide spectrum of skin diseases was identified, which were e‑mail: [email protected] caused by both the hemoglobin disorder and the complications of treatment. Patients and methods Received 07 August 2018 Revised 10 September 2018 This cross‑sectional study included 105 Egyptian patients (50 female individuals and 55 male Accepted 23 September 2018 individuals) with transfusion‑dependent β‑thalassemia major in the period spanning from June Published 25 March 2020 2017 to February 2018. The study was performed on child and adult patients of β‑thalassemia Menoufia Medical Journal 2020, 33:267–271 who presented to the hematology clinic, Menoufia University hospital. Skin examination of each patient was carried out, and any skin disease present was recorded. Results The main skin disorders that were noticed in decreasing order of frequency were pruritus (34.4%), xerosis (24.8%), urticaria (21.1%), freckles (17.1%), tinea infections (11.6%), pitriasis alba reported in 10.5%, scars (10.5%), hypersensitivity to deferoxamine pump (9.5%), herpes simplex (9.5%), acne vulgaris (8.6%), miliaria (6.7%), contact dermatitis (4.8%). Conclusion Skin diseases were frequent among patients with β‑thalassemia major. The most common skin lesions in our patients were pruritus, xerosis, and hyperpigmentation. Careful skin examination of thalassemia patients is required to provide early diagnosis of dermatological diseases and a better quality of life.

Keywords: β‑Thalassemia, cutaneous manifestations, iron overload, pruritus, xerosis

β Introduction condition [3,4]. ‑Thalassemia major affects multiple organs and is associated with considerable morbidity β‑Thalassemia is a blood disorder that reduces the and mortality. In β‑thalassemia, a wide spectrum of production of hemoglobin. Hemoglobin is the skin diseases was identified, which were caused by iron‑containing protein in red blood cells that carries both the hemoglobin disorder and the complications oxygen to cells throughout the body. In people with of treatment [5]. A lot of literature has been written on β‑thalassemia, low levels of hemoglobin lead to a lack of various aspects of β‑thalassemia, but little information oxygen in many parts of the body. Affected individuals about the cutaneous manifestation of this disease. The also have a shortage of red blood cells (anemia), which aim of this study was to document the frequency of can cause pale skin, weakness, fatigue, and more serious β β skin diseases among patients with ‑thalassemia major complications [1]. ‑Thalassemia is a fairly common to help rapid treatment and prevent complications. blood disorder worldwide. Thousands of infants with β‑thalassemia are born each year. β‑Thalassemia occurs most frequently in people from Mediterranean countries, North Africa, the Middle East, India, Patients and methods Central Asia, and Southeast Asia [2]. Thalassemia This cross‑sectional study was carried out on patients of is caused by faulty genes that affect the production β‑thalassemia who presented to Menoufia University of hemoglobin. A child can only be born with the hospital during the period spanning from June 2017 condition if they inherit these faulty genes from both to February 2018. The study was conducted on 105 parents. For example, if both parents have the faulty gene that causes β‑thalassemia major, there’s a 25% This is an open access journal, and articles are distributed under the terms chance of each child they have being born with the of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 condition. The parents of a child with the condition License, which allows others to remix, tweak, and build upon the work are usually carriers of thalassemia. This means they non‑commercially, as long as appropriate credit is given and the new only have one of the faulty genes that causes the creations are licensed under the identical terms. 1110-2098 © 2020 Faculty of Medicine, Menoufia University DOI: 10.4103/mmj.mmj_247_18 [Downloaded free from http://www.mmj.eg.net on Thursday, January 14, 2021, IP: 156.204.184.20]

268 Menoufia Medical Journal, Volume 33 | Number 1 | January-March 2020

Table 1 Demographic characteristics of the studied groups transfused β‑thalassemia major patients. The study was β Sociodemographic data n (%) performed on child and adult patients of ‑thalassemia Sex who attended to Menoufia University hospital. All Male 55 (52.4) patients underwent detailed history evaluation, Female 50 (47.6) including age, sex, and duration of illness. All patients Age (years) were examined to record any dermatological disorders. Mean±SD 18.4±13.3 The patients did not complain about having any Range 2-50 skin problems, but skin lesions were discovered on examination. Table 2 Duration of thalassemic disease in the patients of the study The work was started after obtaining approval from Duration of the disease the department of dermatology and andrology and Mean±SD 16.5±4.6 Range 1-59 years the research ethics committee of Menoufia Faculty of Medicine. A self‑report questionnaire was given to participants after obtaining their consent. The xerosis (24.8%), urticaria (21.1%) freckles (17.1%), questionnaire was designed by the investigator. tinea infections (11.6%), pitriasis alba reported Each patient was examined and asked to fill the in 10.5%, scars (10.5%), hypersensitivity to questionnaire to ensure that all gathered information deferoxamine pump (9.5%), herpes simplex (9.5%), was kept confidential and the participant would be kept acne vulgaris (8.6%), miliaria (6.7%), and contact anonymous; each questionnaire was handed over in an dermatitis (4.8%), as shown in Table 3. envelope, and, after filling it, the participant sealed the envelope and put it in a basket containing other sealed envelopes. Discussion All patients in the study had thalassemia for more than Thalassemia is one of the most common single‑gene 1 year. This study included 105 patients aged from 2 disorders worldwide, in which hemoglobin beta chain to 60 years, as thalassemia major, which is the severe production is decreased. Today, the life expectancy of form of thalassemia, becomes apparent before 2 years thalassemia patients is increased because of a variety of age, but thalassemia intemedia and thalassemia of treatment methods; however, treatment‑related minor are less severe and will appear later in life. We complications have also increased. Profound anemia excluded patients who were more than 60 years of age, and severe hemosiderosis cause functional and immune‑compromised patients due to other causes such physiological abnormalities in various organ systems. as diabetes mellitus, hepatitis C virus and AIDS, and This study was conducted to assess the frequency of patients with other associated blood or immunological cutaneous and mucosal manifestations in patients with β disease, to avoid other manifestations caused by aging, ‑thalassemia [6]. lowered immunity and other blood diseases. Iron overload causes significant morbidity and The results were collected and entered into the computer mortality in patients with transfusion‑dependent β using SPSS (statistical package for the social sciences) ‑thalassemia [7]. The higher standards of care in β program for statistical analysis (version 20; Inc., ‑thalassemia have led to a significant increase in Chicago, Illinois, USA). the life expectancy in severely affected patients. Enhanced years of survival have led to the unmasking Descriptive statistics in the form of mean, SD, number of management‑related complications, which were and % were applied. infrequently encountered [8].

Pruritus, which occurred in 34.3% of our patients, was the most common cutaneous abnormality. Our finding Results is close to a Turkish study [9], which found that 37.2% The study was performed on 105 patients of of thalassemia patients had pruritus. β‑thalassemia; female individuals comprised 52.4% while male individuals comprised 47.6% of patients The pathogenesis of pruritus is unknown. It might be Table 1. The duration of thalassemic disease ranged due to the release of histamine from tissue mast cells from 1 to 59 years (Table 2). secondary to stimulation by iron deposits in the skin [10].

The main skin disorders that were noticed in Dry skin is known as xerosis. The condition is decreasing order of frequency were pruritus (34.4%), characterized by pruritic, dry, cracked, and fissured [Downloaded free from http://www.mmj.eg.net on Thursday, January 14, 2021, IP: 156.204.184.20]

Larynx in rheumatoid arthritis Gaber and Galal 269

Table 3 Distribution of skin diseases among enrolled patients (n=105) 34 and 53% of the evaluated patients [12], whereas Skin manifestation n (%) 24.8% of our patients reported this symptom. This Pruritus difference may be related to the prevailing climatic No 69 (65.7) conditions. Yes 36 (34.3) Xerosis In our study, 23.9% of the patients showed No 79 (75.2) pigmentary disorders. Hyperpigmentation is Yes 26 (24.8) generalized and particularly pronounced in the Scar sun‑exposed areas of the face and hands. Most of the No 94 (89.5) affected patients had dark brown hyperpigmentation. Yes 11 (10.5 Fekri et al. have documented a prevalence rate of Pigmentary disorders No 80 (76.2) 28% for skin pigmentation in their patients with Bronze color 1 (1.0) thalassemia [13]. Freckle 18 (17.1) PIH 6 (5.8) Postinflammatory hypopigmentation was observed in Hypersensitivity to deferoxamine pump our patients; it was 5.8%. It is close to the study by No 95 (90.5) Jiquan et al., which was 6.4%. Its etiology is unknown; Yes 10 (9.5) however, solar exposure and genetic predisposition Verruca vulgaris have been hypothesized as causative factors. It is No 96 (91,4) usually associated with guttate hyperkeratosis, xerosis, Yes 9 (8,6 ) and lentiginosis [14]. Tinea infections No 93 (88,6) Several immunological defects have been found in T. circinate 4 (3.9) TVS 8 (7.7) thalassemia patients [15]. Repetition of transfusions Herpes simplex for the treatment of thalassemia major provokes the No 95 (90.5) patient’s immune system and results in the production Yes 10 (9.5) of antierythrocyte antibodies (alloantibodies and/or Urticaria autoantibodies) [16]. No 83 (79.0) Yes 22 (21.0) Urticaria and contact dermatitis, which were seen in our Pitriasis alba patients (21 and 4.8%, respectively), could be explained No 94 (89.5) in this way, whereas urticaria and contact dermatitis Yes 11 (10.5) were 16.7 and 13%, respectively [17]. Contact dermatitis No 100 (95.2) Our study ranked ephelides as the fifth most frequently Yes 5 (4.8) observed disorder (17.1%), whereas Taher and sheikh- Acne No 101 (96.2) Taha reported it as the most common disorder seen in Yes 4 (3.8) their patients (70.7%) [18]. Ephelides in thalassemia Other manifestation patients might be explained by iron deposition in the Chilblains 1 (1.0) skin [19]. Hair fall 1 (1.0) Impetigo 2 (1.9) Tinea infections are typically acquired directly from Miliaria 7 (6.7) contact with infected humans or animals, or indirectly Purpura 1 (1.0) from exposure to contaminated soil or fomites. In Scabies 1 (1.0) our study, 11.6% of our patients complained of PIH, post-inflammatory hyperpigmentation; TVS, Tenia versicolour. tenia infections, whereas 5.1% was reported by the Turkish study [20]. skin with scaling. The appearance of xerotic skin is like cracked porcelain. These cracks or fissures are present Eleven of our patients (10.5%) had pityriasis alba. Low because of epidermal water loss. The skin splits, and levels of serum copper may account for the occurrence cracks are deep enough to disrupt dermal capillaries, of pityriasis alba. Copper is indispensable to activate and bleeding fissures may occur. Itching or pruritus the tyrosinase in melanocytes, which is critical to occurs, leading to secondary lesions [11]. melanin production [21].

In our study xerosis was the second most frequently Several studies reported reduced serum copper in observed skin disorder (24.8%). The reported frequency thalassemia patients [22]. Pityriasis alba was reported of xerosis among thalassemia patients ranges between as 6–4% by the Turkish study [23]. [Downloaded free from http://www.mmj.eg.net on Thursday, January 14, 2021, IP: 156.204.184.20]

270 Menoufia Medical Journal, Volume 33 | Number 1 | January-March 2020

In this study, scars were observed in 10.5%. Scars Freckles were also more common; therefore, the patient were hypopigmented, and the abdomen was the most should use sun screen to prevent it. Symptomatic frequently affected area, followed by the lower limbs. treatment and dermatological consultation are very Six patients had scars caused by the deferoxamine important. pump. A previous study in Iran reported that scars occurred in 28% of thalassemia patients [24]. Financial support and sponsorship In our study, hypersensitivity to deferoxamine pump was Nil. noted in 95% of the participants. Turkish study incidence of hypersensitivity to deferoxamine pump Conflicts of interest was 12.8% [25]. There are no conflicts of interest. Reduction in serum zinc levels, as a result of deferoxamine therapy, has been described by previous studies. This might be the cause of skin disorders found References in thalassemia patients receiving deferoxamine [26]. 1 Wonke B. Clinical management of beta‑thalassemia major. Semin Hematol 2001; 38:350–359. 2 Akhavan‑Niaki H, Derakhshandeh‑Peykar P, Banihashemi A, In our study, verruca vulgaris was observed in 8.6% Mostafazadeh A, Asghari B, Ahmadifard MR, et al. A comprehensive of our patients, but, in the study by Dogram and molecular characterization of beta thalassemia in a highly heterogeneous population. Blood Cells Mol Dis 2011; 47:29–32. collegaues, it was observed in 1.8% of patients. In this 3 Thein SL. The molecular basis of β‑thalassemia. Cold Spring Harb study, herpes simplex and miliaria were noticed in 9.5 Perspect Med. 2013; 3:a011700. and 6.7%, respectively, but Dogram and collegaues did 4 Galanello R, Origa R. Beta‑thalassemia. Orphanet J Rare Dis 2010; 5:11. not observe any cases. 5 Galanello R. Deferiprone in the treatment of transfusion‑dependent thalassemia: a review and perspective. Ther Clin Risk Manag 2007; 3:795–805. In this study, acne was observed in 3.8% of our patients; 6 Naderi M, Shamshiri H, Alizadeh S. Cutaneous and mucosal manifestations we believed that this was a result of the age of the study in patients with beta major thalassemia. Dermatol Cosmet 2013;4:27–33. participants, rather than being caused by thalassemia 7 Rund D, Rachmilewitz E. Beta‑thalassemia. N Engl J Med 2005; 353:1135–1146. itself. Our finding is close to the Turkish study, which 8 Panigrahi I, Agarwal S. Thromboembolic complications in beta‑thalassemia: was 2.6% of the study group [27]. beyond the horizon. Thromb Res 2007; 120:783–789. 9 Dogramaci AC, Savas N, Ozer B. Skin diseases in patients with Some studies, for example, those conducted by beta‑thalassemia major. Int J Dermatol 2009; 48:1057–1061. 10 Brigant F, Hautefeuille V, Dadban A. Generalized pruritus in dysmetabolic Baccarani and collegaues and Aessopos et al. [28], hyperferritinemia treated by phlebotomy. Dermatol Online J 2015; 21:pii. have revealed that pseudoxansoma elasticum‑like skin 11 Norman RA. Xerosis and pruritus in the elderly: recognition and lesions are common in patients with β‑thalassemia management. Dermatol Ther 2003; 16:254–259. major. However, we did not observe any patient with 12 Momeni A, Adabi M, Amin Javaheri M. Skin and mucosal manifestations in patients with thalassemia major. JBUMS 2001; 3:38–46. pseudoxansoma elasticum‑like skin lesions in our 13 Fekri A, Shamsaddini S, Maghsoodloonejad A. Skin and mucous study. The difference may be attributed to the ethical membrane lesions in major B‑thalassemia. Iran J Dermatol 2000;12:7–17. and regional differences between the two study 14 Jiquan S, Khalaf AT, Jinquan T. Necrobiosis lipoidica: a case with histopathological findings revealed asteroid bodies and was successfully populations [28]. treated with dipyridamole plus intralesional triamcinolone. J Dermatol Treat 2008; 19:54–57. 15 Lombardi G, Matera R, Minervini MM. Serum levels of cytokines and soluble antigens in polytransfused patients with beta‑thalassemia major: Conclusion relationship to immune status. Haematologica 1994; 79:406–412. 16 Sadeghian MH, Keramati MR, Badiei Z. Alloimmunization among Dermatological findings are frequent in Egyptian transfusion‑dependent thalassemia patients. Asian J Transfus Sci 2009; patients with thalassemia major. The most common 3:95–98. 17 Sherief LM, Abd El‑Salam SM, Kamal NM. Nutritional biomarkers in skin lesions in our patients were pruritus, xerosis, children and adolescents with beta‑thalassemia‑major: an Egyptian center and hyperpigmentation. Careful skin examination experience. Biomed Res Int 2014; 2014:261761. 18 Taher A, Sheikh‑Taha M, Koussa S. Comparison between deferoxamine of thalassemia patients is required to provide early and deferiprone (L1) in iron‑loaded thalassemia patients. Eur J Haematol diagnosis of dermatological diseases and a better 2001; 67:30–34. 19 Rivella S. β‑Thalassemias: paradigmatic diseases for scientific discoveries quality of life. and development of innovative therapies. Haematologica 2015; 100:418– 430. Iron overload is the cause of most skin problems; hence, 20 Ratnavel RC, Squire RA, Boorman GC, Faergemann J, Gupta AK, iron chelators are very important. The most common Al Mofadi A, et al. Dynamics of dermatophytosis frequency in Mexico: an analysis of 2084 cases. Med Mycol 2009; 48:476–479. manifestation is pruritus; therefore, antihistamines and 21 Miazek N, Michalek I, Pawlowska‑Kisiel M. Pityriasis alba – common soothing lotions may be useful. Xerosis was the second disease, enigmatic entity: up‑to‑date review of the literature. Pediatr manifestation; thus, emollient will be good treatment. Dermatol 2015; 32:786–791. [Downloaded free from http://www.mmj.eg.net on Thursday, January 14, 2021, IP: 156.204.184.20]

Larynx in rheumatoid arthritis Gaber and Galal 271

22 Shamshirsaz AA, Bekheirnia MR, Kamgar M. Metabolic and endocrinologic 25 Dubey AP, Parakh A, Dublish S. Current trends in the management of complications in beta thalassemia major: a multicenter study in Tehran. beta thalassemia. Indian J Pediatr 2008; 75:739–743. BMC Endocr Disord 2003; 3:4 26 Galanello R, Campus S. Deferiprone chelation therapy for thalassemia 23 Gupta MA, Gupta AK. Stressful major life events are associated with a major. Acta Haematol 2009; 122:155–164. higher frequency of cutaneous sensory symptoms: an empirical study of 27 Baccarani‑Contri M, Bacchelli B, Boraldi F. Characterization of non‑clinical subjects. J Eur Acad Dermatol Venereol 2004; 18:560–565. pseudoxanthoma elasticum‑like lesions in the skin of patient with 24 Nolte F, Ho¨chsmann B, Giagounidis A. Results from a 1‑year, open‑label, beta‑thalassemia. J Am Acad Dermatol 2001; 44:33–39. single arm, multi‑center trial evaluating the efficacy and safety of oral deferasirox in patients diagnosed with low and int‑1 risk myelodysplastic 28 Aessopos A, Savvides P, Stamatelos G. Pseudoxanthoma elasticum‑like syndrome (MDS) and transfusion‑dependent iron overload. Ann Hematol skin lesions and angioid streaks in beta‑thalassemia. Am J Hematol 1992; 2013; 92:191–198. 41:159–164.