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 Table of Contents  
LETTER TO EDITOR
Year : 2021  |  Volume : 7  |  Issue : 1  |  Page : 44-45

Bosentan: A newer option to treat digital ulcers in patients of systemic sclerosis


Department of Skin and VD, Patna Medical College, Patna, Bihar, India

Date of Submission03-May-2020
Date of Decision20-Nov-2020
Date of Acceptance15-Jan-2021
Date of Web Publication25-Jun-2021

Correspondence Address:
Pankaj Kumar Tiwary
Department of Skin and VD, Patna Medical College, Patna, Bihar
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdd.ijdd_27_20

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How to cite this article:
Deb S, Tiwary PK, Singh A. Bosentan: A newer option to treat digital ulcers in patients of systemic sclerosis. Indian J Drugs Dermatol 2021;7:44-5

How to cite this URL:
Deb S, Tiwary PK, Singh A. Bosentan: A newer option to treat digital ulcers in patients of systemic sclerosis. Indian J Drugs Dermatol [serial online] 2021 [cited 2021 Dec 2];7:44-5. Available from: https://www.ijdd.in/text.asp?2021/7/1/44/319353



Sir,

Systemic sclerosis is a complex autoimmune disease characterized by cutaneous and visceral fibrosis with multisystem vascular pathology that may be complicated by ischemic digital ulcers (DUs).[1],[2] Although the etiopathogenesis of the disease is not fully understood, increased endothelin-1 activity has been considered to have a role in the pathogenesis of the vascular component. Potential therapeutic agents for the management of DU include calcium channel blockers; α adrenergic blockers, angiotensin-converting enzyme inhibitor, and others. Bosentan is a dual endothelin receptor antagonist which binds both ETA and ETB receptors, thereby inhibiting endothelin-1. It also has favorable effect on micro- and macrovascular hemodynamic and severity of digital fibrosis, therefore can be used as a treatment modality.

A 45-year-old female presented with complaints of bluish discoloration associated with burning sensation of fingers on exposure to cold since 15 years. It was followed by tightness of skin which started from fingers and extend patent ductus arteriosus ed to involve the hands, progressing till mid-arm length, both legs extending proximally to involve thighs, and also involves the face. Chest and back were relatively spared. Morning stiffness affecting both small and large joints was present. There was a history of digital ulceration on fingers and toes, followed by self-mutilation of few digits 7 years back. She presented to us with complaint of new ulceration for the past 3 months over the left hand and right foot, not associated with any systemic complaints pertaining to gastrointestinal or respiratory system. Cutaneous examination revealed face to have a tight, taut skin, pinched nose, and reduced mouth opening giving mask-like appearance. Hands showed mutilation of index finger of the right hand, middle finger of the left hand associated with destruction of terminal phalanx of the fourth toe of left foot. Other fingers were also pale, swollen, and stiff at tips of them. Flexion deformity in both 5th digits of hand was present. New ulcers were seen over index finger left hand on distal phalanx [Figure 1]a, 2nd and 5th toe of right foot [Figure 1]b tests.
Figure 1: (a) Digital tip ulcers over fingers. (b) Digital ulcers over toes

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EULAR score was calculated 28 and MODIFIED RODNAN SCORE: 28. Systemic examination of the patient revealed bilateral basal crepts. Routine investigations performed (complete blood count, serum electrolyte, liver function test (LFT), renal function test, and routine examination of urine) were all within normal limits. ANA showed positive results. Specific Antibody tests reported, a positive anti centromeric antibody, but negative anti-Scl-70 Antibody. Both electrocardiogram(ECG) and Echocardiogram(ECHO) evaluations were within normal limit reflecting a normal functioning of heart. But on evaluation of pulmonary capacity, Spirometry showed obstruction features. High resolution computed tomography(HRCT) chest or esophageal manometry could not be done for the patient. chest and esophageal manometry could not be performed. The patient was initially prescribed with several oral vasodilators including nifedipine, losartan, and cilastazole along with fluoxetine in variable doses, but suboptimal response was achieved and she continued to complain of intractable pain and crippling morning stiffness. She was previously treated with three cycles of dexamethasone cyclophosphamide pulse 3 years back, and since then she was on tapering doses of steroids along with pentoxyphylline 400 mg TDS and nifedepin 10 mg BD for the past 2 years. She also had a 3-month course of sildenafil citrate a year back because of development of new ulcers but experienced only partial control of symptoms. Even when she was on multiple vasodilators, she started developing new DUs along with recurrent episodes of Reynolds phenomenon. Hence, continuing the previous medications, Bosentan 62.5 mg BD was introduced after performing LFTs. After continuing the treatment for 3 months, marked improvement was noted in the gangrenous ulcers of both hand and foot [Figure 2]a and [Figure 2]b. Most of the ulcers healed with notable improvement in pain and paresthesia over fingers. There was no change in EULAR score as ulcers were replaced by digital scars. The patient complained of no side effects, and LFT was unaltered after 3 months of therapy.
Figure 2: (a) Healing of fingertip ulcers after treatment. (b) Healing of ulcers over toes after treatment

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DUs are a very disabling complication of systemic sclerosis. Cause of ulcer in systemic sclerosis is multifaceted including microangiopathy, microtrauma, fibrosis, and calcinosis. Endothelin 1, a highly potent vasoconstrictor secreted from the endothelial cells, is known to play a major role in vasculopathy of the disease. Bosentan, an endothelin antagonist, has been claimed as an emerging agent that is supposed to arrest progression of ulcers and help to prevent the development of new ones.[3],[4],[5],[6] The studies RAPIDS-1 and RAPIDS-2(Randomized Placebo Controlled Investigation of Digital ulcers in Scleroderma) also gives similar evidential support on the use of Bosentan for treatment of digital ulcers in scleroderma which are not responding to conventional protocols.[7],[8] Bosentan is generally prescribed for short course of 4–6 months. In our patient of diffuse cutaneous systemic sclerosis, Bosentan showed spectacular results with healing of existing ulcers. We kept the follow-up period of 4 months, during which no new ulcers were reported. Remarkable improvement in our patient supports the previous few observations of accelerating wound healing in DUs in case of systemic sclerosis patients with Bosentan treatment, and Bosentan can be safely used to aid into treatment of such nonhealing ulcers in patients of systemic sclerosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Hamaguchi Y. Autoantibody profiles in systemic sclerosis: Predictive value for clinical evaluation and prognosis. J Dermatol 2010;37:42-53.  Back to cited text no. 1
    
2.
Steen V, Denton CP, Pope JE, Matucci-Cerinic M. Digital ulcers: Overt vascular disease in systemic sclerosis. Rheumatology (Oxford) 2009;48 Suppl 3:19-24.  Back to cited text no. 2
    
3.
Sapadin AN, Fleischmajer R. Treatment of scleroderma. Arch Dermatol 2002;138:99-105.  Back to cited text no. 3
    
4.
Denton CP. Therapeutic targets in systemic sclerosis. Arthritis Res Ther 2007;9:S6.  Back to cited text no. 4
    
5.
Rubin LJ, Black CM, Denton CP, Seibold JR. New therapeutic strategies for systemic sclerosis: A critical analysis of the literature. Clin Dev Immunol 2005;12:165-73.  Back to cited text no. 5
    
6.
Charles C, Clements P, Furst DE. Systemic sclerosis: Hypothesis-driven treatment strategies. Lancet 2006;367:1683-91.  Back to cited text no. 6
    
7.
Korn JH, Mayes M, Matucci Cerinic M, Rainisio M, Pope J, Hachulla E, et al. Digital ulcers in systemic sclerosis: Prevention by treatment with Bosentan, an oral endothelin receptor antagonist. Arthritis Rheum 2004;50:3985-93.  Back to cited text no. 7
    
8.
Matucci-Cerinic M, Denton CP, Furst DE, Mayes MD, Hsu VM, Carpentier P, et al. Bosentan treatment of digital ulcers related to systemic sclerosis: Results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial. Ann Rheum Dis 2011;70:32-8.  Back to cited text no. 8
    


    Figures

  [Figure 1], [Figure 2]



 

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