Evaluation of dexamethasone pulse therapy in systemic sclerosis

QM Ahmad, I Hassan, I Majid

 Dept. of Dermatology, STD & Leprosy, Govt. Medical College and Associated SMSH Hospital, Srinagar, Kashmir (J&K), India

Correspondence Address:
Q M Ahmad
House No. 214, Karan Nagar, Srinagar, Kashmir (J&K)
India

Introduction

The treatment of systemic sclerosis is still far from being satisfactory and no single drug has shown a consistent benefit in this disease.[1] Steroid pulses have been tried in different diseases of autoimmune cause including systemic sclerosis perse.[2] We have been treating our patients of systemic sclerosis with monthly pulses of dexamethasone over the last two years. Many of these patients have completed 12 or 18 monthly pulses and majority of these patients have shown a remarkable improvement in their symptom profile as well as in their objective signs including skin sclerosis.

Materials and Methods

25 patients of systemic sclerosis have been enrolled in the present open study till this date. All of these patients are females with age ranging from 19 years to 60 years. Out of these 25 patients, 10 have been put off the pulse therapy after receiving twelve to eighteen monthly pulses. Rest of the fifteen patients are presently continuing with their pulse therapy, being at different stages of the same.

All these patients were admitted to the hospital at the initiation of the pulse therapy. Pretreatment assessment included a thorough clinical examination for extent and severity of skin sclerosis, and for any evidence of systemic involvement including the lungs, oesophagus and renal systems.

The patients were clinically assessed for the extent and severity of skin sclerosis, for any evidence of involvement of lungs, the G.I.T and the renal systems by way of the presence of breathlessness, dysphagia, edema, oliguria or hematuria. Any clinical evidence of an overlap syndrome was also noted down. Pretreatment investigations included a complete hemogram including ESR, urinalysis, kindney function tests , blood sugar estimation, a complete collagen vascular profile including ANA and LE cell phenomenon, an electrocardiogram, X-rays of the chest, hands and feet and pulmonary function tests. The weight of each individual patient was also recorded at the initiation of pulse therapy and a photograph of the face, hand and feet was also taken.

Before starting the therapy, a representative skin biopsy was taken from the fingers for histopathological examination.

After the pretreatment assessment, the patients were put on an intravascular infusion of 50mg of dexamethasone in 500ml of 5% dextrose on three consecutive days in the hospital. The same treatment was then repeated after every month after admitting the patients in the hospital.

In between the pulses, the patients were given vasodilator therapy in the form of nifedipine with or without other vasodilators in a dosage depending upon the severity of symptoms in each individual patient.

The parameters that were recorded at each monthly pulse treatment were any symptomatic improvement in Raynaud′s phenomenon, breathlessness, dysphagia, and also any improvement in skin sclerosis. A note was also made of emergence of any side effects including weight gain, acid peptic symptoms, precipitation or aggravation of infections etc.

Each patient was given twelve to eighteen month pulse depending upon the improvement shown by every individual patient.

After completing twelve to eighteen pulses the patients were assessed once again with regard to their presence and severity of breathlessness, Raynauds′s phenomenon, dysphagia, digital ulcers, gangrenous changes (if any) and also skin sclerosis. The weight of every individual patient was also noted down and pulmonary function tests, hemogram, ESR, X-rays of hands, feet and also a representative skin biopsy from the finger was also repeated in each individual case.

The improvement in each of these individual was noted down.

Results

Out of the 25 patients who have been enrolled for the present study, 10 have completed the pulse therapy while 15 others are still in the treatment receiving stage. All of these patients have shown an improvement in their symptomatology as well as in their objective signs. In this paper however, we will discuss only the results obtained in patients who have completed their pulse treatment and are on follow up presently. The results attained in these 10 patients are discussed as under:

1) Raynaud′s phenomenon:

Out of 10 patients who have complete the pulse therapy, 6 have shown a marked improvement in Raynaud′s phenomenon, 3 other have shown a moderate improvement and the remaining 1 a mild improvement in the same.

2) Breathlessness:

A marked improvement was seen in moderate in another 1 and mild improvement in 3 patients as far as breathlessness is concerned. One patient (aged 21 years) didn′t complain c breathlessness even at the start of therapy.

3) Digital ulcerations:

Digital ulcers responded markedly in out of 9 patients (one patient was free from digital ulceration even after completion of pulse therapy and in this patient both the hands were deformed from severe skin sclerosis.

4) Extent and severity of sclerosis

This was another marker, which showed a very satisfactory response to pulse therapy. There was a marked response in 3 patients, moderate improvement in 6 patients and a mild improvement was seen in one patient in the severity and extent of skin sclerosis. The response was also quantified objectively by means of pre and post treatment skin biopsies. On comparing the histopathology; marked decrease in dermal fibrosis and significant growth of skin appendages was seen the post treatment biopsies in all but one of the! patients.

5) Gastrointestinal symptoms

Gastrointestinal symptoms, evidenced by the presence of dysphagia and other related symptoms was present in 3 patients only. All the patients showed a mild to moderate improvement in these symptoms following pulse treatment.

6) Laboratory findings:

A complete hemogram including ESR, well as pulmonary function tests were repeated after the completion of pulse therapy and these parameters also showed a favourable response. While pulmonary function tests showed a mild to moderate improvement in 7 patients (70% of total) the ESR showed a consistent decrease in all of these patients.

7) Adverse effects

Adverse effects in the form of weight gain, osteoporosis, acid peptic symptoms, glucose intolerance, reactivation of infections etc were also monitored during the pulse treatment. One patient developed tubercular cervical lymphadenopathy during the therapy (there was no history of tuberculosis in the past), one patient showed an abnormal weight gain and another developed prominent acid peptic symptoms during the therapy.

Discussion

The ideal therapy for systemic sclerosis is, at present, only 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.[1],[3] No therapy has shown to reverse the pathological changes seen in systemic sclerosis.[2] Steroid pulse therapy has been used in many immune mediated disorders like pemphigus, bullous pemphigoid, systemic lupus erythematosus, rheumatoid arthritis, pyoderma gangrenosum etc.[5],[6] There have also been some preliminary reports of a beneficial effect of steroid pulse therapy in systemic sclerosis but unfortunately these only too few a number of patients.[2]

We have been treating our patients of systemic sclerosis with the same therapy since the last one and a half years and our experience has been that of a positive response in the majority of the patients. In our experience we have observed that patients start showing symptomatic improvement within the first 3-6 months only with resolution of digital ulcers and scarring, a reduction in breathlessness and an overall improvement in subjective well being. The overall response shown varies from patient to patient but we have found a definite correlation of the overall response with the stage of the disease at initiation of therapy. Patients in whom the therapy was started early in the disease at initiation of therapy. Patients in whom the therapy was started early in the disease process had shown a much better overall response than those with an advanced disease at the time of onset of therapy. In addition to the symptomatic improvement in our patients we have documented objective evidence of an improvement in the form of disappearance of pitted scarring, an improvement in skin sclerosis, pulmonary function tests, ESR and histopathological examination of the skin.

Another factor that was heartening to observe is that these patients after completing their pulse treatments, continued to show the initial improvement on follow up. The ten patients who have been put off the pulse are on continuous follow up and none of them has shown a relapse or reversal of the improvement achieved during the pulse therapy.

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