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   Material and Methods
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STUDIES
Year : 1993  |  Volume : 59  |  Issue : 4  |  Page : 168-171

Oral colchicine in chronic plaque psoriasis




Correspondence Address:
Prasanta Bassak


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Source of Support: None, Conflict of Interest: None


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  Abstract 

Colchicine is well known for its antimitotic and anti-inflammatory effects. This study was designed to evaluate the role of oral colchicine in chronic plaque psoriasis. Fifty adults with chronic plaque psoriasis were randomly allocated into 2 groups of 25 patients each. Group A received oral colchicine 2 mg/day in 2 divided doses, while Group B patients were given placebo tablets. Patients were evaluated every week and the final result compiled after 8 weeks. 90% patients in Group A had gastrointestinal intolerance necessitating a reduction in dose of colchicine to 1 mg/day. After 8 weeks the lesions improved significantly in Group - A patients, compared to Group B (t=2.815, p<0.01). Apart from gastrointestinal intolerance and nephrotic syndrome, no other significant side effects were encountered. It may be worthwhile trying this drug in chronic plaque psoriasis recalcitrant to conventional topical treatment.


Keywords: Psoriasis, Colchicine


How to cite this article:
Bassak P, Chatterjee A. Oral colchicine in chronic plaque psoriasis. Indian J Dermatol Venereol Leprol 1993;59:168-71

How to cite this URL:
Bassak P, Chatterjee A. Oral colchicine in chronic plaque psoriasis. Indian J Dermatol Venereol Leprol [serial online] 1993 [cited 2020 May 26];59:168-71. Available from: http://www.ijdvl.com/text.asp?1993/59/4/168/3921



  Introduction Top


Colchicum was first utilized by Baron von Storck of Vienna in 1763 for the treatment of acute gout. [1] Later the alkaloid colchicine was isolated from the plant autumn crocus (colchicum autumnale) in 1820. [2] Since then, Colchicine has been tried in a variety of dermatologic disorders.' Psoriasis was one of the first dermatosis treated with oral colchicine. [3]

There are remarkably few studies advocating the therapeutic efficacy of oral colchicine in chronic plaque psoriasis. [3],[4] We report here a prospective single-blind, randomized clinical trial designed to evaluate the efficacy of the drug in the Indian context.


  Material and Methods Top


Fifty adults diagnosed clinically as chronic plaque psoriasis were selected and randomly allocated into 2 groups (A and B), of 25 patients each. Baseline investigations included a routine haemogram and urine analysis. Excluded from the study were pregnant females, persons working under direct sunlight and those with a history of remission during autumn/winter- which was the period of trial. None were on any form of oral or topical medication for at least 4 weeks prior to the study.

Group A included 20 males and females in the age group 20-45 years. They received oral colchicine 2 mg/day in 2 divided doses after food. Group B patients included 17 males and 8 females in the age range 25-40 years, who were given multivitamin tablets twice daily as a placebo. Patients in both groups were instructed to liberally apply coconut oil twice daily on the lesions as an emollient. Patients were evaluated every week and the parameters erythema, scaling, induration and pruritus recorded on a 0 to 3 scale.

The total duration of the study was 8 weeks and the baseline investigations were repeated at the end of each month.


  Results Top


In Group A, 1 patient defaulted after the 1st week of therapy and was dropped [Table - 1]. Another patient developed colchicine induced nephrotic syndrome after 2 weeks of therapy. Colchicine was withdrawn and the patient recovered with systemic steroids. This patient was also not included in the subsequent analysis. Of the remaining 23 patients, 20 (86.9%) developed gastrointestinal (GI) intolerance during the 1st week of therapy in the form of abdominal fullness, flatulence and diarrhea and the dose of colchicine had to be reduced from the second week onwards to 1 mg/day. This dose was well tolerated and apart from occasional mild crampy abdominal pain and nausea, there were no significant GI upsets.

Clinical improvement of the psoriatic plaques was discernable in Group A only after the second week [Figure - 1]. Scaling became appreciably less from the 3rd week and there was considerable reduction of induration at the end of the 4th week. At 8 weeks, lesions were barely palpable though there was no complete remission in any of the patients. Reduction in erythema score was observed over 8 weeks though mild to moderate erythema of the lesions persisted even at the end of the trial. The grading of pruritus was difficult owing to the purely subjective nature of this parameter. While the majority of patients (69.6%) reported an increase in pruritus during the 1st 4 weeks, subsequently it decreased in intensity but nevertheless persisted throughout the trial. However the grading of pruritus was left out of the statistical analysis to avoid subjective bias. There was no difference in the ultimate clinical outcome between those who received colchicine in the dose of 1 mg/ day and the 3 patients who were able to continue colchicine at 2 mg/day.

The results in group B was less than satisfactory. Though a reduction in scaling over the first 2 weeks was seen,, there was no appreciable change in the erythema, induration or pruritus during the study period.

The erythema, sealing, induration (ESI) scores in group A and B were compared by student 't' test and a significant improvement in group A was shown, p<0.01 [Table - 1].


  Comments Top


One of the characteristic histologic features of psoriatic lesions is the infiltration of the epidermis by numerous neutrophils. [5] Furthermore, it has been shown that the migration of neutrophils into the upper dermis is the earliest histological change, preceding the usual signs of epidermal hyperproliferation. [6] Psoriatic scale contains leukotactic substances that appear to be products of compliment activation. [7] Psoriatic plaque epidermis contains a greater amount of proteinase which induces the accumulation of neutrophils by activating compliment in contrast to uninvolved epidermis. [8] Thus the migration of activated neutrophils into the skin could play an important role in the pathogenesis of psoriatic lesions. [9]

Colchicine, a microtubule disruptive agent, is effective in inhibiting the chemotactic migration of neutrophils both in vivo [10]sub and in vitro. [11] The potent antimitotic activity of the drug is due to failure of spindle formation and arrest of cell division in metaphase. [12] This drug has been extensively used in the prophylactic treatment of gouty arthritis [13] and familial  Mediterranean fever More Details. [14] At the low dosage in which it is used in the above mentioned condition, colchicine therapy is considered to be safe even when administered over long periods of time.

Colchicine is extremely toxic: the most common toxic effects of this drug are nausea, vomiting, abdominal pain and diarrhoea. Gastrointestinal disturbances occur in about 80% of patients. [1] The incidence of such toxicity in our series was 86.9%. Malkinson and Lynfield [3] recommends 2-3 mg/day of oral colchicine in psoriasis and we initially chose the lower figure for our patients. But even with the lower dose advocated, the drug was poorly tolerated by our patients. Wahba and Cohen, [4] however, were more specific in titrating the dose. They recommended 0.02 mg/kg/day. Thus an average 50 kg adult would require 1 mg/day which was the modified dose we used and was well tolerated. Other reported toxicities of oral colchicine include bone marrow depression, alopecia, hepatic failure, mental depression, seizures, ascending paralysis, respiratory depression and death. [14] Apart from nephrotic syndrome, we did not encounter any of the above problems. We do not share the observations by Malkinson and Lynfield [3] that oral colchicine results in a remarkable improvement of psoriasis but are in agreement with Wahba and Cohen, [4] who noted that thin plaques responded better than chronic, stable, thick plaque lesions although decreased scaliness, erythema and infiltration and marked diminition of pruritus was observed in all cases. At best, we would venture to comment that oral colchicine is better than a placebo, though no complete remission is to be expected. Perhaps it may be worth a try with oral colchicine, in recalcitrant chronic plaque psoriasis prior to considering other potentially harmful antimitotic drugs.

 
  References Top

1.Aram H. Colchicine in dermatologic therapy. Int J Dermatol 1983; 22 : 566-9.  Back to cited text no. 1  [PUBMED]  
2.Flower RJ, Moncada S, Vane JR. Analgesic - antipyretic and anti inflammatory agents, drugs employed in the treatment of gout. In : The Pahrmacologic basis of Therapeutics (Goodman GA, Goodman L, Rail TW, eds), 6th edn. New York : MacMillan Publishing Company, 1980, 718.  Back to cited text no. 2    
3.Malkison FD, Lynfield YL.. Colchicine alopecia. J Invest Dermatol 1959; 33 371.  Back to cited text no. 3    
4.Wahba A, Cohen H. Therapeutic trials with oral colchicine in psoriasis. Acta Derm­Venereol (Stockh) 1980; 60 : 515-20.  Back to cited text no. 4  [PUBMED]  
5.Ackerman AB. Subtle clues to diagnosis by conventional microscopy. Am J Dermatol Pathol 1979; 1 : 69-75.  Back to cited text no. 5    
6.Chowaniec O, Jablonska S. Pre-pin-point papule changes preceding pin-point lesions of psoriasis. Acta Derm-Venereol (Stockh) 1979; 59:Suppl. 85 : 39-45.  Back to cited text no. 6    
7.Tagami H, Ofuji S. Demonstration of C3 cleavage products in leukotactic substances of scale extract from pustular psoriasis. Br J Dermatol 197,7; 96:94-5.  Back to cited text no. 7    
8.Lazarus GS, Yost FJ, Thomas DA. Polymorphonuclear leukocytes: possible mechanism of accumulation in psoriasis. 1/1 Science 1977; 198:1162-3.  Back to cited text no. 8    
9.Lazarus GS, Gilgor RS. Psoriasis, Polymorphonuclear leukocytes and lithium carbonate. Arch Dermatol 1979; 115:1183­4.  Back to cited text no. 9  [PUBMED]  
10.Caner JEZ. Cochicine inhibition of chemotaxis. Arthritis Rheum 1965; 8 : 757­60.  Back to cited text no. 10    
11.Malawista SE, Howell RR, Seegmiller JE. Factors modifying the inflammatory response to injected microcrystalline sodium urate. Arthritis Rheum 1962; 5:307.  Back to cited text no. 11    
12.Wilkinson JD, McKenzie AW, Wilkinson DS. Treatment. In: Recent Advances in Dermatology (Champion RH) No.7. Edinburgh Churchill Livingstone, 1986;194-5.  Back to cited text no. 12    
13.Yu TF, Gutman AB. Efficacy of Colchicine prophylaxis in gout. Ann Intern Med 1961, 55:179-92.  Back to cited text no. 13  [PUBMED]  
14.Zemer D, Revach M, Pras M, et al. A controlled trial of Colchicine in preventing attacks of familial Medeterranean fever. New Eng J Med 1974; 291:932-4.  Back to cited text no. 14  [PUBMED]  


    Figures

[Figure - 1]

    Tables

[Table - 1]

This article has been cited by
1 The Course of Chronic Plaque-Type Psoriasis in Placebo Groups of Randomized Controlled Studies
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Archives of Dermatology. 2004; 140(3): 338-344
[Pubmed]



 

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