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THERAPEUTIC ROUND
Year : 2010  |  Volume : 55  |  Issue : 4  |  Page : 355-358
Dexamethasone pulse therapy in patients of systemic sclerosis: Is it a viable proposition? A study from kashmir


1 Department of Dermatology, STD and Leprosy, Government Medical College, Srinagar, Jammu and Kashmir, India
2 Department of Internal Medicine, Government Medical College, Srinagar, Jammu and Kashmir, India

Date of Web Publication4-Jan-2011

Correspondence Address:
Iffat Hassan
Department of Dermatology, STD and Leprosy, Government Medical College, Karan Nagar, Srinagar - 190 010, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.74543

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   Abstract 

Background: Systemic sclerosis is a multisystemic autoimmune disorder. Intravenous dexamethasone pulse therapy has been used since 1998. Aim: The aim was to report the beneficial effects of dexamethasone pulse in patients of systemic sclerosis vis--vis the side effects. Materials and Methods: Forty-seven patients of systemic sclerosis were included. After looking at the history and physical examination, the patients were submitted to various relevant investigations. Clinical scoring of the patient was done at baseline and 6-month interval according to Furst's organ indices score. Results: A total of 47 patients of systemic sclerosis were included (45 females, 2 males). In majority, acrosclerosis was seen. Severe sclerosis and contractures were seen in two patients. Moderate proteinuria, restrictive lung disease, dysphagia, and valvular heart involvement were seen. A total of 13 patients on dexamethasone pulse therapy developed tuberculosis. Improvement in skin scoring and decreased severity of Raynaud's phenomenon was seen. No improvement in dysphagia, severe vascular symptoms, or restrictive lung disease was seen. Conclusion: Thus, beneficial effects of dexamethasone pulse therapy seem to be merely cosmetic.


Keywords: Dexamethasone pulse, Raynaud′s phenomenon, systemic sclerosis


How to cite this article:
Sameem F, Hassan I, Ahmad QM, Khan D, Majeed I, Kamili M A, Shah PA. Dexamethasone pulse therapy in patients of systemic sclerosis: Is it a viable proposition? A study from kashmir. Indian J Dermatol 2010;55:355-8

How to cite this URL:
Sameem F, Hassan I, Ahmad QM, Khan D, Majeed I, Kamili M A, Shah PA. Dexamethasone pulse therapy in patients of systemic sclerosis: Is it a viable proposition? A study from kashmir. Indian J Dermatol [serial online] 2010 [cited 2019 Sep 24];55:355-8. Available from: http://www.e-ijd.org/text.asp?2010/55/4/355/74543



   Introduction Top


Systemic sclerosis is a multisystemic autoimmune disorder affecting predominantly the skin, lungs, gut, and kidneys. The criteria to be fulfilled for labeling a patient as a case of systemic sclerosis (established by the Subcommittee for Scleroderma Criteria of the American Rheumatology Association) include one major criterion, i.e., sclerosis of skin proximal to the digits including the face, limbs, neck, or trunk and/or two or more minor criteria which are (1) sclerodactyly, (2) digital pitted scarring, and (3) bilateral lower zone (basal) pulmonary fibrosis. [1]

Treatment options include vasodilators, immunosuppressants and antifibrotics. [2] Steroids in the form of intravenous dexamethasone pulse (DP) therapy were recommended and have been used in the Department of Dermatology, STD and Leprosy, SMHS (associated teaching hospital of Government Medical College, Srinagar) since 1999. [3],[4] The aim of our study was to report our experience regarding the beneficial effects of dexamethasone pulse therapy in patients of systemic sclerosis vis-ΰ-vis the side effects of the therapy.


   Materials and Methods Top


Forty-seven patients of systemic sclerosis admitted in the in-patient wing of the Department of Dermatology, STD and Leprosy, SMHS Hospital, Srinagar, during 1998-2005 were included in the study. The diagnosis of systemic sclerosis was made on the basis of the ARA criteria. A complete history especially regarding the presence of Raynaud's phenomenon, dysphagia, and dyspnea was taken into account. A detailed physical examination including recording the weight, pulse, and blood pressure, and examination of chest (measuring the chest expansion and auscultation for basal crepitations), cardiovascular system, and abdomen were done. This was followed by a meticulous cutaneous examination with particular attention toward scoring the sclerosis of skin on the basis of Furst's score, examining digital pitted ulcers, cutaneous calcinosis, gangrene of fingers and toes, contractures, and auto-amputations. Next the patients were submitted to a battery of investigations including complete hemogram with erythrocyte sedimentation rate [ESR (fasting)], renal function tests (KFT), blood sugar (fasting), estimation of serum electrolytes, liver function test (LFT) with enzymes, chest X-ray [CXR (PA view)], electrocardiogram (ECG) all leads, X-ray hands and feet bilaterally, and urine analysis. Before starting therapy, a representative skin biopsy from fingers was sent for histopathological examination. Opthalmological checkup for ocular tension and visual acuity was done along with upper GI endoscopy or barium swallow, high-resolution CT scan (HRCT) (if afforded), 24-h urinary protein, creatinine clearance, electromyography, echocardiography, pulmonary function tests, stool for occult blood, serum iron, and total iron binding capacity (TIBC). A complete collagen vascular profile was done: VDRL, LE cells, ANA, RA factor, anti-ds DNA, anti-RNP, anti-topoisomerase, anti-centromere, and creatinine phosphokinase (CPK) levels. All these investigations were done at baseline. CBC with ESR, KFT, urine exam, and BP recording was done monthly; 24-h urinary protein and CXR were repeated in 6 months. Skin scoring by Furst's scoring was also repeated in 6 months. The clinical scoring of the patient was done at baseline and at 6 months according to Furst's organ indices score. [5],[6],[7],[8] Carbon monoxide diffusion capacity could not be measured due to the nonavailability of facilities for the same.

After the pretreatment assessment, patients were put on intravenous infusions of 100 mg dexamethasone in 500 ml of Dextrose 5% on three consecutive days per month.


   Results Top


A total of 47 patients of systemic sclerosis were included in the study. They included 45 females and 2 males (F:M ratio of 23:1). The age range of patients was 18-60 years (average age of presentation was 40 years). Of the females, 41 were married with a noncontributory obstetric history. Of the males, 1 was a tailor (he was advised to change his occupation) and the other a farmer. The duration of disease prior to presentation ranged from 1 month to 25 years. Fifteen patients were grossly underweight for height. Among the associated medical conditions were diabetes (1), hypertension (2), Hashimoto's thyroiditis (1), and Graves' disease (1). Two patients gave a previous history of pulmonary tuberculosis with anti-tubercular therapy intake (>3 years before).

The skin scores ranged from 5/30 to 20/30. In majority of the patients, localized cutaneous systemic sclerosis with acrosclerosis alone was seen [Figure 1] and [Figure 2]. Diffuse cutaneous systemic sclerosis with severe sclerosis and contractures was seen in two patients only. In one female patient, hyperpigmentation and hypertrichosis of skin were seen (Addison's disease and porphyria were ruled out by investigations).
Figure 1 :Sclerosis of face with radial furrowing

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Figure 2 :Digital pitted scarring in the same patient

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Four patients had evidence of proximal myopathy - clinical, biochemical (raised CPK, and LDH levels), and electromyographic. These four patients were given a revised diagnosis of mixed connective tissue disease (MCTD). Moderate proteinuria was seen in four patients. Severe restrictive lung disease was seen in three patients. Dysphagia was seen in four patients, of whom three showed endoscopic evidence of antral gastritis or duodenitis.

Significantly, echocardiographic evidence of valvular heart involvement was seen in five patients which included mitral regurgitation (2), mitral stenosis (2), atrial regurgitation (2), and patent ductus arteriosus (1). Arrythmias including ventricular premature contractions, bradycardia, and heart blocks on ECG was seen in five patients. Evidence of pulmonary arterial hypertension (PAH) - loud pulmonic sound and P wave pulmonale (P pulmonale) on ECG - was seen in five patients. [9] Three patients had severe anemia (two with severe iron deficiency, serum iron being 7-32 mg/ml only, stool for occult blood negative).

The patients were put on dexamethasone pulse therapy (only 43 patients as those with MCTD were excluded from the study). One patient developed steroid psychosis after receiving first DP (48-year-old postmenopausal female with no past history of psychiatric problem). One patient developed ischemic necrosis of the head of femur (32-year-old married female). In these patients, further DP was withheld.

Seven patients on DP therapy on monthly follow-up had persistent asymptomatic pyuria. Their urine was sent for routine bacterial culture. This was negative. AFB culture of urine sample, ESR and polymerase chain reaction (PCR) of the urinary sediment for mycobacteruim tuberculosis was then sent to exclude genitourinary tuberculosis. Of these, five patients had PCR positive for M. tuberculosis. Most of these patients had taken 8-12 DPs. Four patients had chest symptoms in the form of dry cough/cough with expectoration. Chest auscultation revealed crepitations. Sputum was sent for AFB on three consecutive days. CXR (PA view) was repeated. Bronchoalveolar lavage (BAL) with AFB staining and PCR of the lavage fluid was done. All four had BAL positive pulmonary tuberculosis. These patients had taken longer therapy (24 pulses). One patient developed FNAC proven tubercular lymphadenitis (cervical) after three DPs. One patient succumbed to miliary tuberculosis after three DPs. [10]

Two patients developed chronic renal failure in spite of DP therapy. One patient developed malignant hypertension after 7 DPs with a grave outcome. There were three deaths: one of CRF, one of miliary TB, and one of unexplained causes (she was 27-year-old married female with severe vascular symptoms and a very poor response to DP therapy).

Improvement in skin scoring, decreased severity of Raynaud's phenomenon, and healing of digital ulcers was definitely seen. However, two patients with severe vascular symptoms continued to develop gangrene of toes requiring amputations even after 12 and 17 DPs, respectively. No improvement in dysphagia was seen in the four patients at the end of 12 and 24 DPs. Four patients with a severe restrictive lung disease showed no improvement in dyspnea or pulmonary function tests even after 14-18 DPs.


   Discussion Top


The ideal therapy for systemic sclerosis is at present conjectural and there is no universal agreement over the choice of therapy, the stage at which it is to be started, and the goals to be achieved by the therapy. Steroid pulse therapy has been used in many immune-mediated disorders like pemphigus, bullous pemphigoid, systemic lupus erythmatosus, rheumatoid arthritis, and pyoderma gangrenosum.

Pai et al.[3] used DP therapy in systemic sclerosis but unfortunately only in too few number of patients. They reported some beneficial effects of steroid pulse therapy in systemic sclerosis. Masood et al. have reported the preliminary results of DP therapy in systemic sclerosis. [4] At the time of the previous communication from our department, only 25 patients of systemic sclerosis had been included in the study. The dose of dexamethasone used was 50 mg in Dextrose 5% intravenously over 3 days/month for 12-18 pulses only. In their study of 10 patients completing therapy, there was reported to be an improvement in Raynaud's phenomenon (marked in 6/10, moderate in 3/10, mild in 1/10). Digital ulcers responded markedly in 8/9 patients. Sclerosis improved markedly in 3/10, moderately in 6/10, and mildly in 1/10 patients and this was assessed visually, on palpation and on pre- and post-treatment biopsies of skin. Improvement in breathlessness and dysphagia was seen in previously symptomatic patients. Among adverse effects, tubercular cervical lymphadenopathy in one, abnormal weight gain in one, and acid peptic disease in one patient were seen. This study was taken further since then with a few modifications:

  1. Dose of dexamethasone was increased to 100 mg.
  2. Duration of therapy was extended till the time of maximal improvement (i.e., till no further improvement was seen even after six more pulses).
  3. Furst's organ indices scoring method for pretreatment assessment and for monitoring the response to treatment was used. [5],[6]


In our study, majority of our patients had localized cutaneous systemic sclerosis (CREST) with predominantly vascular symptoms. These vascular symptoms could be managed by symptomatic therapy and were not potentially life threatening. Moreover, two patients with severe vascular symptoms continued to develop gangrene requiring amputation after 12 and 17 pulses. Also patients with a severe variant of systemic sclerosis (as indicated by renal, pulmonary, or cardiac involvement or anemia) showed no improvement over baseline even after 12-24 DPs. Of the10 patients on follow-up of the previous study, [4] 6 developed disease activity again after 1-2 years. Two patients developed CRF and one malignant HT even after 12 DPs. Four patients developed pulmonary tuberculosis and five patients developed genitor urinary tuberculosis after therapy. [10] Hence, the beneficial effects of DP therapy in systemic sclerosis seem to be merely cosmetic and need to be weighed against the limitations and side effects therein.

Hence, DP therapy has been discarded in our center and a revised organ-specific treatment schedule has been adopted. This includes calcium channel blockers, low-dose aspirin, pentoxyphylline, losartan or fluoxetine for Raynaud's phenomenon, ACE inhibitors for PAH, hypertension or renal crisis, methotrexate for severe skin induration, cyclophosphamide for interstitial lung disease, and antifibrotics (d-penicillamine or colchicines for skin induration). [5],[6],[7],[8]

 
   References Top

1.Rowell NR, Good Field MJ. In: Champion RH, Burton JL, Burns DA, Breathnach SM, editors. The connective tissue disease in Rook/Wilkinson/Ebling Text book of Dermatology. 6 th ed, Vol. 3. Oxford: Blackwell Science publications; 1998. p. 2520-45.  Back to cited text no. 1
    
2.Muller LU, Benning K, Lang B. Current therapy of systemic sclerosis (scleroderma). Clin Investig 1993;71:257-63.  Back to cited text no. 2
    
3.Pai BS, Srinivas CR, Sabitha L, Shenoi SD, Balachandran CN, Acharya S. Efficacy of dexamethasone pulse therapy in systemic sclerosis. Int J Dermatol 1995;34:726-8.  Back to cited text no. 3
[PUBMED]    
4.Ahmad QM, Hassan I, Majid I. Evaluation of dexamethasone pulse therapy in systemic sclerosis. Indian J Dermatol Venereol Leprol 2003;69:76-8.  Back to cited text no. 4
[PUBMED]  Medknow Journal  
5.Clements PJ, Lachenbruch PA, Ng SC, Simmons M, Sterz M, Furst DE. Skin score. A semi quantitative measure of cutaneous involvement that improves prediction of prognosis in systemic sclerosis. Arthritis Rheum 1990;33:1256-63.  Back to cited text no. 5
[PUBMED]    
6.Furst DE, Clements PJ, Harris R, Ross M, Levy J, Paulus HE. Measurement of clinical changes in progressive systemic sclerosis: A one year double blind placebo controlled trial of N-acetylcysteine. Ann Rheum Dis 1979;38:356-61.  Back to cited text no. 6
[PUBMED]  [FULLTEXT]  
7.Furst DE, Clements PJ, Hillis S, Lachenbruch PA, Miller BL, Sterz MG, et al. Immunosuppresion with chlorambucil versus placebo for scleroderma.Arthritis Rheum 1989;32:584-93.  Back to cited text no. 7
[PUBMED]    
8.Furst DE, Clements PJ, Saab M, Sterz MG, Paulus HE. Clinical and serological comparison of seventeen chronic progressive systemic sclerosis and seventeen CREST syndrome patients matched for sex, age and disease duration. Ann Rheum Dis 1984;43:794-801.  Back to cited text no. 8
[PUBMED]  [FULLTEXT]  
9.Ahmad QM, Shah IH, Nauman Q, Sameem F, Kamili MA. Cardiac involvement in patients of systemic sclerosis. Indian J Dermatol 2008;53:215-6.  Back to cited text no. 9
[PUBMED]  Medknow Journal  
10.Ahmad QM, Shah IH, Nauman Q, Farah S, Javaid S. Increased incidence of tuberculosis in patients of systemic sclerosis on dexamethasone pulse therapy: A short communication from Kashmir. Indian J Dermatol 2008;53:24-5.  Back to cited text no. 10
[PUBMED]  Medknow Journal  


    Figures

  [Figure 1], [Figure 2]

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