Systemic sclerosis presents its cutaneous manifestations with innovative triple therapeutic regime


  • Thamir Kubaisi University of Anbar
  • Khalifa Sharquie Department of Dermatology, College of Medicine, University of Baghdad, Center of Dermatology, Medical City Teaching Hospital, Baghdad, Iraq.
  • Inas Sharquie Department of Microbiology & Immunology, College of Medicine, University of Baghdad, Baghdad, Iraq


Systemic sclerosis, Zinc sulfate, Shiny skin, Calcinosis cutis, Triple therapy


Objective To record and evaluate the different cutaneous manifestations of all patients with an established diagnosis of systemic sclerosis and to have a new therapeutic trial.   Methods This is a cross-sectional descriptive clinical study with a therapeutic trial that was conducted during the period from 2014 to 2023. All patients with a well-established diagnosis of systemic sclerosis were evaluated for various skin manifestations. A triple therapeutic trial was carried out using oral zinc sulfate, sildenafil, and prednisolone.   Results The main early presenting symptoms were the sensation of coldness usually cold hands and feet seen in 25 (100%) cases, followed by dusky blue red hands and feet observed in 23(92%) cases, followed by difficult hands movement and stiffness together with loss of facial expression in 21 (84%) of patients. Later on, patients mentioned hardening of the face and hands skin with the enhanced shininess of the face. Also pitting scarring of pulps and tips of fingers and sometimes toes could be considered as early symptoms of the disease, seen in 25 (100%) of patients. While the most striking findings on examination were shiny hardening of skin which was most prominent on the face and hands. Difficulty in opening the mouth and protruding the tongue was also a common finding that was detected in 19 (76%) cases. Angiomatous macules and papules of the face were rarely seen as observed only in 3 (12%) female patients. Pitting the pulps and tips of fingers were very early striking findings and very helpful diagnostic signs for diagnosis. Calcinosis cutis commonly affecting elbows were observed as late findings that commonly associated with necrosis of tissue and infections and only observed in 2 (8%) cases.   Conclusion Systemic sclerosis usually manifests in cold weather and patients complain of coldness especially on hands and feet with hardening of the skin. Pitting and scarring of the tips of fingers are significant diagnostic findings that are often followed by ischemic changes. While facial angiomatous macules and papules, calcinosis cutis, and rippling pigmentation with leukoderma were detected lately. Triple therapy showed its effectiveness in improving the complaints of patients.  


Gintrac M. Note sur la sclerodermie. Rev Med Chir Paris. 1847;2(1847):2

van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. Classification criteria for systemic sclerosis: an ACR-EULAR collaborative initiative. Arthritis and rheumatism. 2013;65(11):2737

Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. New England Journal of Medicine. 2009;360(19):1989-2003

Varga J, Abraham D. Systemic sclerosis: a prototypic multisystem fibrotic disorder. The Journal of clinical investigation. 2007;117(3):557-67

Wollheim F. Classification of systemic sclerosis. Visions and reality. Rheumatology. 2005;44(10):1212-6

Sobolewski P, Maślińska M, Wieczorek M, Łagun Z, Malewska A, Roszkiewicz M, et al. Systemic sclerosis–multidisciplinary disease: clinical features and treatment. Reumatologia/Rheumatology. 2019;57(4):221-33

Krieg T, Takehara K. Skin disease: a cardinal feature of systemic sclerosis. Rheumatology. 2006;48(suppl_3):iii14-iii8

Sampaio AL, Bressan AL, Vasconcelos BN, Gripp AC. Skin manifestations associated with systemic diseases–Part I. Anais Brasileiros de Dermatologia. 2022;96:655-71

von Kobyletzki G, Uhle A, Pieck C, Hoffmann K, Altmeyer P. Acrosclerosis in patients with systemic sclerosis responds to low-dose UV-A1 phototherapy. Archives of dermatology. 2000;136(2):275-6

Pattanaik D, Brown M, Postlethwaite BC, Postlethwaite AE. Pathogenesis of systemic sclerosis. Frontiers in immunology. 2015;6:272

Brown M, O’Reilly S. The immunopathogenesis of fibrosis in systemic sclerosis. Clinical & Experimental Immunology. 2019;195(3):310-21

Rosendahl AH, Schönborn K, Krieg T. Pathophysiology of systemic sclerosis (scleroderma). The Kaohsiung Journal of Medical Sciences. 2022;38(3):187-95

Truchetet ME, Brembilla NC, Chizzolini C. Current concepts on the pathogenesis of systemic sclerosis. Clinical reviews in allergy & immunology. 2021:1-22

Viswanath V, Phiske MM, Gopalani VV. Systemic sclerosis: current concepts in pathogenesis and therapeutic aspects of dermatological manifestations. Indian journal of dermatology. 2013;58(4):255

Asano Y. The pathogenesis of systemic sclerosis: an understanding based on a common pathologic cascade across multiple organs and additional organ-specific pathologies. Journal of clinical medicine. 2020;9(9):2687

Bournia VKK, Vlachoyiannopoulos PG, Selmi C, Moutsopoulos HM, Gershwin ME. Recent advances in the treatment of systemic sclerosis. Clinical reviews in allergy & immunology. 2009;36:176-200

Al-Adhadh RN, Al-Sayed TA. Clinical features of systemic sclerosis. Saudi medical journal. 2001;22(4):333-6

Vitiello M, Abuchar A, Santana N, Dehesa L, Kerdel FA. An update on the treatment of the cutaneous manifestations of systemic sclerosis: The dermatologist's point of view. The Journal of clinical and aesthetic dermatology. 2012;5(7):33

Bibi Nitzan Y, Cohen AD. Zinc in skin pathology and care. Journal of dermatological treatment. 2006;17(4):205-10

Sharquie IK, Sharquie KE, Al-bassam WW. Zinc as an essential element for normal immune reactions and as a therapeutic agent for autoimmune diseases. Journal of Pakistan Association of Dermatologists. 2022;32(4):719-25

Sharquie KE, Al-Jaralla FA, Sharquie IK. Intralesional Injection of Hyaluronic Acid as a Long Lasting Therapy of Morphea Sclerosis. American Journal of Dermatology and Venereology. 2019;8(3):45-8

Sharquie KE, Najim RA, AL‐DORI WS, AL‐HAYANI RK. Oral zinc sulfate in the treatment of Behcet's disease: A double blind cross‐over study. The Journal of dermatology. 2006;33(8):541-6

Sharquie K, Najim R, Farjou I, Al‐Timimi D. Oral zinc sulphate in the treatment of acute cutaneous leishmaniasis. Clinical and experimental dermatology. 2001;26(1):21-6

Al‐Gurairi F, Al‐Waiz M, Sharquie K. Oral zinc sulphate in the treatment of recalcitrant viral warts: randomized placebo‐controlled clinical trial. British Journal of Dermatology. 2002;146(3):423-31

Sharquie KE, Najim RA, Al-Hayani RK, Al-Nuaimy AA, Maroof DM. The therapeutic and prophylactic role of oral zinc sulfate in management of recurrent aphthous stomatitis (ras) in comparison with dapsone. Saudi medical journal. 2008;29(5):734-8

Sharquie KE, Noaimi A, Shwail E. Oral zinc sulphate in treatment of alopecia areata (double blind; crossover study). J Clin Exp Dermatol Res. 2012;3(150):1000150

Sharquie KE, Noaimi AA, Kadir NO. Topical therapy of xeroderma pigmentosa with 20% zinc sulfate solution. The Iraqi Postgraduate Medical Journal. 2008;7:231-6

Sharquie KE, Najim RA, Al‐Salman HN. Oral zinc sulfate in the treatment of rosacea: a double‐blind, placebo‐controlled study. International journal of dermatology. 2006;45(7):857-61

Gorial FI, Swady RN. Prevalence of Depression in Iraqi Patients with Systemic Sclerosis and Its Relationship with Disease Severity. International Journal of Medical Research & Health Sciences. 2018;7(4):69-74

Chung L, Fiorentino D. Digital ulcers in patients with systemic sclerosis. Autoimmunity reviews. 2006;5(2):125-8

Fox P, Chung L, Chang J. Management of the hand in systemic sclerosis. Journal of Hand Surgery. 2013;38(5):1012-6

Zhu JL, Black SM, Chen HW, Jacobe HT. Emerging treatments for scleroderma/systemic sclerosis. Faculty Reviews. 2021;10

Starnoni M, Pappalardo M, Spinella A, Testoni S, Lattanzi M, Femino R, et al. Systemic sclerosis cutaneous expression: Management of skin fibrosis and digital ulcers. Annals of Medicine and Surgery. 2021;71:102984

Distler JH, Allanore Y, Avouac J, Giacomelli R, Guiducci S, Moritz F, et al. EULAR Scleroderma Trials and Research group statement and recommendations on endothelial precursor cells. Annals of the rheumatic diseases. 2009;68(2):163-8

Koenig M, Joyal F, Fritzler MJ, Roussin A, Abrahamowicz M, Boire G, et al. Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud's phenomenon to systemic sclerosis: a twenty‐year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology. 2008;58(12):3902-12

Ferri C, Valentini G, Cozzi F, Sebastiani M, Michelassi C, La Montagna G, et al. Systemic sclerosis: demographic, clinical, and serologic features and survival in 1,012 Italian patients. Medicine. 2002;81(2):139-53

Robertson L, Marshall R, Hickling P. Treatment of cutaneous calcinosis in limited systemic sclerosis with minocycline. Annals of the rheumatic diseases. 2003;62(3):267-9

Fries R, Shariat K, von Wilmowsky H, Böhm M. Sildenafil in the treatment of Raynaud’s phenomenon resistant to vasodilatory therapy. Circulation. 2005;112(19):2980-5

Shenoy PD, Kumar S, Jha LK, Choudhary SK, Singh U, Misra R, et al. Efficacy of tadalafil in secondary Raynaud’s phenomenon resistant to vasodilator therapy: a double-blind randomized cross-over trial. Rheumatology. 2010;49(12):2420-8




How to Cite

Kubaisi T, Sharquie K, Sharquie I. Systemic sclerosis presents its cutaneous manifestations with innovative triple therapeutic regime. J Pak Assoc Dermatol [Internet]. 2023Oct.12 [cited 2023Nov.28];33(4):1385-93. Available from:



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