Dr Ramji Gupta

Dexamethasone Cyclophosphamide Pulse Therapy in Rheumatoid Arthritis

 

The effects of various treatment modalities available for treatment of rheumatoid arthritis are transient, short lived and are not able to produce prolonged or permanent remission.

Five patients of rheumatoid arthritis were given intravenous Dexamethasone Cyclophosphamide Pulse (DCP) therapy which consists of dexamethasone 100 mg dissolved in 5%, 500 ml glucose and transfused over 1-1.5 hours for 3 consecutive days every month and cyclophosphamide 500 mg on day one and 50 mg daily orally in between the pulses. All the 5 patients are in clinical cure without any treatment for the last 2-6 years.  

 

Salient features of all 5 cases are as follow. 

Case-1

A-60- year old female had sero-positive rheumatoid arthritis with pain in both elbows, wrists, both interphalyngial and metacarpophalyngial joints, knees, ankles and metatarso-phalyngial joints of 2 months duration. She also had morning stiffness of 15 minutes duration. There were no joint deformities. There was no improvement with nimesulide 100 mg and paracetamol 500 mg twice daily taken for 1 month. Rheumatoid factor was positive (220 iu/ml) with positive CRP. ANF was negative. ESR was 47 mm. At this juncture DCP was started along with diclofenac sodium 200 mg daily. After 3rd pulse, there was about 40% improvement in joints pain without any effect in morning stiffness. Chlorzoxazone 1.5 gm daily was added. After 6 DCP pain improve further by 60% and morning stiffness disappeared completely. During next 2 months (after 8 DCP) there were no pain in hands, wrists, elbows, knees, ankles and feet when diclofenac, paracetamol and chlorzoxazone was all stopped. DCP was continued for another 9 months without any pain when it was stopped. Cyclophosphamide 50mg daily was also stopped after 9 months. There was no recurrence of pain in joints during half yearly follow- up for the next 6 years. ESR and CRP were repeated every 6th months which were within normal limit. Rheumatoid factor at the end of the treatment was found negative. 

 

Case-2

A-45- year old male presented with pain in hands, feet, shoulders with swelling and tenderness of left wrist, both metacarpophalyngial joints and left foot of 6 months duration. CRP and rheumatoid factor were positive (240 IU/ml). ESR was 32 mm. ANF was negative, X-ray chest, hands and ultrasound of abdomen was normal. Naproxen 500-750 mg daily for 5-6 weeks showed no effect on pain and swelling. At this juncture DCP therapy was started. After 2nd DCP pain and swelling reduced by about 50% which further improved with subsequent pulses. After 4th DCP there was no swelling and pain in any joints. ESR was 7 mm when naproxen was also stopped. DCP was continued for another 9 months without any recurrence of pain in joints, when it was stopped. Cyclophosphamide 50 mg was also stopped after 9 months. There was no recurrence of swelling or pain in any joints followed- up half yearly by the author for 6 years. Rheumatoid factor was negative with normal ESR and CRP at the end of the study.

 

Case-3

A 60- year-old female with sero-positive rheumatoid arthritis presented with pain in her shoulders, wrists, interphalyngial, metatarsophalyngial and hip joints of 4 year duration which use to improve with ibuprofen, paracetamol taken off and on. There was a sudden increase in pain in all the above joints with morning stiffness of 1-hour duration since 3 months. ESR was 37 mm with positive CRP and negative ANF and ASO titer. Rheumatoid factor was positive (240IU/ml). X-ray both hands showed rarified bone with degenerative changes. There was slight improvement during the next 15 days in pain with chlorzoxazone 1.5 gm, paracetamol 900 mg and hydroxychloroquine hydrochloride 200 mg daily. DCP therapy was started at this point along with diclofenace sodium 100 mg daily. After 2nd DCP, pain in joints disappeared. Morning stiffness also disappeared which reappeared after 3 weeks. Pain and morning stiffness of all joints disappeared after 4th DCP when declofenac sodium was stopped. There was no pain or stiffness during the next 9 months with ESR 10 mm and negative CRP, when DCP was stopped. Cyclophosphamide 50 mg daily was continued for another 9 months without any relapse of pain in joints when it was also stopped. Rheumatoid factor repeated after 6, 12 and 18 months  was found negative with normal ESR 10mm. X-ray both hands still showed decreased mineralization with normal joints space. There was no pain or stiffness in any joints during next 5 year without any treatment.

 

Case-4

A 30-year- old female started  pain and swelling of her right index finger, wrist and knee which progress to involve left shoulder, ankle, wrist, elbow, knee ,metatarsophalyngial  joints of both feet and interphalyngial joint of her both hand in 2 years duration with morning stiffness of 2 hours duration. X-ray of all joints showed no erosion of any bone. Rheumatoid factor (41.8 I U/ml) and AntiCCP (13.50unit/ml) was positive with ESR 69mm 1st hour. CRP was negative (4.2mg/l). She was started methotrexate 20mg and methylprednisolone 12mg weekly, hydroxychloroquine 400mg  and paracetamol 650mg daily. Pain in all joints disappeared  in 15 days and stiffness in 1 month. During the next 6 months methylprednisolone was reduce and stopped. However she developed pain in ankle and wrist joints during next 7 days. Methotrexate was increased to 30 mg per week orally along with other above mentioned treatment with mild improvement during next 2-3 weeks. There was relapse in pain in most of the joints during next 5-6 months. At this juncture she switched to homoeopathy and took treatment for 1 year and subsequently to ayurvedic treatment for next 7 months without any relief. At this juncture she was seen by author, she had pain at her right pelvic region, knee, left ankle, wrist, matatarsophalyngial joints of both feet and interphalyngial joint of both hands with morning stiffness of 4-5 hours since 1 year’s duration. ESR was 36 mm with positive Rheumatoid factor (60 1U/ml) and Anti CCP (24.1 unit/ml) with negative CRP. At this juncture pulse therapy with azathioprine was started. There was no morning stiffness after 2nd pulse therapy. Pain in all joints started improving immediately after 1st pulse and cleared completely after 4th pulse therapy.  She was given another 9 pulses without any pain when pulse was stopped. However she continues azathioprine 100 mg daily for another 9 months without any pain in any joints when it was also stopped. There was no recurrence of pain during next 2 year follow-up.

 

Case-5

A 28-years old unmarried female presented with pain in ankles, right knee and left shoulder of 2years duration. X-ray ankle, knee, shoulder and pelvis show no erosion with normal bone.  ESR was 39mm with positive CRP (11.3mg/ml) and Rheumatoid factor (85.14/ml), ASP, ANA and Anti CCP (0.5 unit/ml) was negative. HLA B-27 was negative. There was no improvement with daily paracetamol 650 mg, methylprednisolone 24 mg, chlorzoxazone 1.5gm, hydroxychoroquine 400mg and methotrexate 15-30mg given weekly in different combination during 2 years duration. When seen by the author she was on methotrexate 15 mg orally weekly etoricoxib 60 mg daily, injection methylprednisolone 80 mg intramuscular weekly. Her ESR was 81mm with positive CRP (34.2) and Rheumatoid factor (171.5IU/ml) and negative Anti CCP (0.05v/ml). At this juncture Pulse therapy with azathioprine was started with improvement of pain in all joints and reduction in swelling  after 1st pulse. With subsequent pulses pain in all joints improve slowly and there was no pain in any joints after 12th pulse. Slowly all the drugs was withdrawn phase wise one by one and after 15th pulse she was not having any pain and any drugs except pulse. She continued another 9 pulse without any pain when pulse was stopped. She continued azathioprine 100mg for further 9 months without any pain when azathioprine was also stopped. There was no pain during 2 year follow- up. Laboratory test done at the end showed rheumatoid factor 97.00/ml ,ESR-1 mm/1st hour,  CRP (1.50) , anti CCP(0.50 unit/ml).