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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 7  |  Issue : 1  |  Page : 39-43

“Pigmented irritant contact dermatitis” − an issue of concern due to dithranol misuse in Andaman and Nicobar: an observational study


1 Department of Dermatology, SMIMS, Gangtok
2 Department of Social Work, Hindusthan College of Arts & Science, Coimbatore

Date of Submission21-Mar-2019
Date of Decision12-May-2019
Date of Acceptance26-Sep-2019
Date of Web Publication10-Jul-2020

Correspondence Address:
Dr. Pradeep Balasubramanian
Department of Dermatology, ANIIMS and G.B. Pant Hospital, Port Blair, Andaman and Nicobar Islands

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/Pigmentinternational.Pigmentinternational_

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  Abstract 


Background: Dithranol (anthralin) ointment is a topical medication that is widely being misused by the people in Andaman and Nicobar (A&N) that results in a characteristic irritant reaction. Aim of the study: This study was performed to analyze the various aspects pertaining to the irritant dermatitis due to dithranol misuse such as epidemiological aspects, clinical features, and management. Methodology: The study was done in the Outpatient Department of Dermatology of G.B. Pant Hospital, Port Blair, A&N. This study includes all the patients who presented with irritant reaction due to dithranol ointment and its combination, the clinical features, the common dermatoses in which it is being misused, source of usage (suggested by), and its management and measures undertaken to arrest its misuse. The variables are mentioned as frequency and percentage. Results: The dithranol irritant reaction was commonly seen in the setting of cutaneous dermatophyte infection. Groin was the common site affected. It was commonly encountered among male (76%) and in the age group of 21 to 40 years (75.9%). The medication was commonly suggested by the pharmacists. The “brown stain” due to dithranol was the classical feature seen in all the patients. Conclusion: This study lays emphasis on identifying the irritant reaction due to dithranol ointment through the characteristic “brown stain,” the management of the condition, and the measures that had successfully reduced its misuse. Through the awareness imparted to the pharmacists and the general public, the misuse of the dithranol could be well curtailed in A&N.

Keywords: Andaman and Nicobar, dithranol misuse, pigmented irritant dermatitis


How to cite this article:
Balasubramanian P, Anil AJ. “Pigmented irritant contact dermatitis” − an issue of concern due to dithranol misuse in Andaman and Nicobar: an observational study. Pigment Int 2020;7:39-43

How to cite this URL:
Balasubramanian P, Anil AJ. “Pigmented irritant contact dermatitis” − an issue of concern due to dithranol misuse in Andaman and Nicobar: an observational study. Pigment Int [serial online] 2020 [cited 2020 Oct 24];7:39-43. Available from: https://www.pigmentinternational.com/text.asp?2020/7/1/39/289333




  Introduction Top


Andaman and Nicobar (A&N) group of islands lying in the midst of Bay of Bengal is characterized by high humidity making the prevalence of cutaneous dermatophyte infection higher. Several over-the-counter topical medications are being misused by the patients for dermatophyte infection and also for other indications that is a menace throughout India. Dithranol (anthralin) ointment is one such topical medication, which is being misused by the patients in A&N, that results in a characteristic irritant reaction. This study was performed to analyze the various aspects pertaining to the irritant dermatitis due to dithranol usage such as epidemiological aspects, clinical features, and management.


  Methodology Top


The study was done in the Outpatient Department of Dermatology of G.B. Pant hospital, Port Blair. The study period was from January 2017 to January 2019. This study includes all the patients who presented during the study period with irritant reaction due to dithranol ointment and its combination. Various aspects analyzed were epidemiological features, clinical features, common dermatoses in which dithranol containing preparation was being misused, duration of usage leading to irritant dermatitis, source of usage/suggested by, and its management of dermatitis. The epidemiological factors analyzed were age and gender. The clinical features recorded were duration, site, and morphology of irritant dermatitis. The dermatitis due to dithranol-containing ointment was graded as mentioned in [Table 1]. If there is pus discharge suggestive of secondary bacterial infection, pus was collected in a sterile swab for bacterial culture and sensitivity. The treatment modality of irritant dermatitis was determined by the severity of the dermatitis and the presence of secondary bacterial infection. The variables are mentioned as frequency and percentage.
Table 1 Grading of irritant dermatitis due to anthralin-containing topical medicaments

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  Results Top


Fifty-four patients presented with irritant dermatitis following the usage of dithranol ointment were included in this study. It was predominantly encountered among male (n = 41, 76%). Dithranol dermatitis was witnessed more among those in age group of 21 to 40 years (75.9%). The age distribution of the patients with dithranol irritant dermatitis is mentioned in [Table 2]. All the patients had used the ointment that contains the combination of dithranol 1.15%, salicylic acid 1.15%, and coal tar 5.3%. The duration of usage following which the irritant reaction resulted was 1 to 10 days. The common sites in which the irritant reaction resulted were groin followed by waist, axilla, genitalia, gluteal region, trunk, and face (mentioned in the order of decreasing frequency).
Table 2 Age distribution of patients with dithranol irritant dermatitis

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The dermatitis due to the dithranol ointment and its combination is characterized by the following changes namely “brown-colored stain” involving the affected area that was the most striking change noticed followed by erythema, blistering, superficial skin necrosis, erosions, scaling, oozing, and crusting [Figure 1],[Figure 2],[Figure 3]. Even if there is severe inflammation or erosion, the pigmentation could be well made out as a halo in the surrounding normal skin. Some of the patients had erosions who were secondarily infected leading to pus discharge.
Figure 1 Grade 2 irritant reaction due to dithranol over left cheek following its usage for melasma.

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Figure 2 Grade 3 irritant reaction to dithranol involving the groin and genitalia. The patient had used the ointment to get rid of tinea cruris.

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Figure 3 Resolving grade 3 irritant reaction. The “brown stain” could be made out as a large halo around the areas of resolving erosion.

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The following were the grades of irritant dermatitis due to dithranol: mild dermatitis (grade 1) was seen in 18 patients (33.3%), moderate dermatitis (grade 2) was seen in 24 patients (44.4%), and severe dermatitis (grade 3) was seen in 12 patients (22.2%). Secondary infection characterized by pus discharge from the erosions was seen in four patients (7.4%) with moderate-to-severe dermatitis. The bacterial culture of the pus had grown Staphylococcus aureus in all the four patients. The sensitivity pattern was methicillin sensitive staphylococcus aureus (MSSA) in three and methicillin resistant staphylococcus aureus (MRSA) in one patient.

The patients with mild asymptomatic irritant reaction without any symptoms were not given any treatment except for advice to avoid using the dithranol-containing ointment in the future. The patients with moderate-to-severe dermatitis and patients with symptomatic mild irritant reaction were given short course of topical or oral steroids depending on the severity of the irritant reaction. The patients in whom the erosions were secondarily infected were prescribed a course of oral antibiotics that was later modified as per the culture and sensitivity pattern of the bacterial growth. All the patients responded to the treatment well and got the irritant reaction cleared in less than 1 week. Following the resolution of the irritant reactions, the treatment for the preexistent primary dermatoses was provided.

All the patients were counseled to avoid the usage of topical dithranol-containing medication in the future. The combination of dithranol, salicylic acid, and coal tar was most commonly suggested by the pharmacists whereas the patients had gone to the pharmacists seeking for over-the-counter remedy (n = 46, 85.2%). The rest of the patients with irritant reaction (n = 8, 14.8%) were suggested about the dithranol-containing ointment by their friends and family members.

Cutaneous disorders in which the medicament was commonly being misused are mentioned in the [Table 3]. The dithranol preparation was commonly misused in cutaneous dermatophyte infection (88.9%). The irritant reaction was more markedly witnessed in the groin region and genitalia following the usage of the ointment for tinea cruris.
Table 3 Skin disorders in which the anthralin-containing medication is commonly being misused

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Since dithranol ointment was suggested to majority of the patients by the pharmacists, the name of the pharmacists form where they were dispensed the medicine were obtained from the patients. We had sent letters to those pharmacists to make them aware of the high irritancy potential of the medication (stating the adverse effects of dithranol ointment) and requesting them to avoid dispensing it without any authorized prescription. In addition to this, the author had spread the message to discourage its usage by means of television, radio programs, and newspaper articles. There was an active decline in the incidence of the irritant dermatitis due to dithranol witnessed by the fact that the number of cases of irritant dermatitis due to anthralin has diminished from 46 in the year 2017 to eight in the year 2018, which was gratifying to the author.


  Discussion Top


Dithranol, also called as anthralin, has been used over years as a topical medication for psoriasis. Anthralin was initially extracted from the araroba tree in Brazil over 100 years ago.[1] It was synthesized later on. Anthralin stops the proliferation of keratinocytes in vivo.[2] Anthralin on oxidation results in the synthesis of derivatives such as 9-anthron-10-yl radical, a key intermediate, as well as superoxide and hydroxyl radicals.[2] Further oxidation and polymerization lead to the synthesis of secondary anthralin brown radicals, which is inert. Anthralin-free radicals destroy the DNA of cells and inactivate enzymes associated with cell proliferation and inflammation.[3]

Anthralin is commonly compounded in ointment formulation to increase its stiffness (to prevent the spill over onto the surrounding normal skin).[4] Anthralin is usually combined with salicylic acid as the combination increases the shelf life of anthralin.[5] Anthralin is commonly used in psoriasis and alopecia areata. It is nowadays used as “short contact therapy” to reduce its adverse effects.[6],[7],[8],[9] In the popular Ingram regimen, coal tar bath and exposure to near erythema doses of ultraviolet (UV) light from a mercury vapor lamp was followed by treatment with dithranol in Lassar’s paste applied locally to psoriatic plaques. The modified Ingram method uses selective UVB and short-contact high-potency anthralin therapy in a psoriasis daycare center.[10],[11] Anthralin is also infrequently used in dermatoses such as warts and inflammatory linear verrucous epidermal nevus.[12],[13],[14]

Irritant dermatitis and staining of the skin are the common adverse effects due to anthralin. The irritancy due to anthralin could be reduced by certain measures namely “short-contact therapy,” strictly limiting its application to the affected area with petrolatum or zinc oxide cream applied around the lesional site, gradually increasing the contact duration, compounding it with tar and pretreatment with UVB.[15]

Staining of the skin and clothing are troublesome side effects of anthralin therapy. This is due to oxidation of anthralin to inactive colored compounds (anthraquinone dimer, anthralin dimer, and anthralin conjugates), which bind to keratin and natural and synthetic fibers. The effect is worsened by alkalis. Hence, affected clothes should be rinsed in plain water and not washed with soap.[15],[16] Interestingly, melanosis coli and perianal dermatitis due to ingestion of dithranone (metabolite of anthralin) as a cathartic corresponding to the brown staining of skin and irritant dermatitis with topical anthralin was reported.[15]

The “brown stain” seen in the area of irritant dermatitis is a classical feature that should alert the clinician regarding the possibility of usage of anthralin-containing preparation as witnessed in the patients in the present study. The irritant reaction is more common and marked in the flexural region, genitalia, and face. The high humidity in A&N increases the propensity of irritancy. Dabas et al.[17] has documented that the use of dithranol ointment should be suspected if a patient with dermatophyte infection presents with irritant dermatitis.In the present study, topical and oral steroids helped in bringing down the inflammation commendably and allayed the discomfort of the patients. Reports on the effect of topical corticosteroids on dithranol irritation are largely contradictory.[15] Some studies indicate that the addition of a topical corticosteroid reduces dithranol irritation, whereas others are contradictory.[18],[19],[20]

The usage of topical steroids has become a strong menace leading to the persistence and relapse of cutaneous dermatophyte infection. Anthralin ointment has become a trouble shooter in the recent past in A&N. The irrational dispensing of the ointment by the pharmacist is perturbing. The marked decline in the incidence following the efforts of the author is gratifying.


  Conclusion Top


This study reveals the abrupt increase in the misuse of topical dithranol ointment in A&N. The “brown stain” associated with irritant reaction is the characteristic feature that helps in identifying this problem. Educating the population and pharmacists plays an immense role in curtailing the misuse of such topical medicaments.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Barth J. Introduction of anthralin into dermatology. Int J Dermatol 1992;31:67.  Back to cited text no. 1
    
2.
McGill A, Frank A, Emmett N, Turnbull DM, Birch-Machin MA, Reynolds NJ. The anti-psoriatic drug anthralin accumulates in keratinocyte mitochondria, dissipates mitochondrial membrane potential, and induces apoptosis through a pathway dependent on respiratory competent mitochondria. FASEB J 2005;19:1012-4.  Back to cited text no. 2
    
3.
Schimidt KN, Podda M, Packer L, Baeuerle PA. Anti-psoriatic drug anthralin activates transcription factor NF-Kappa B in murine keratinocytes. J Immunol 1996;156:4514-9.  Back to cited text no. 3
    
4.
Bellis D, Seville RH, Smith JF. Dithranol with salicylic acid in a stiff paraffin base for the treatment of psoriasis. J Clin Pharm Ther 1978;3:7-11.  Back to cited text no. 4
    
5.
Hulsebosch HJ, Ponec-Waelsch M. The interaction of anthralin, salicylic acid and zinc oxide in pastes. Dermatologica 1972;144:287-93.  Back to cited text no. 5
    
6.
Lowe NJ, Ashton RE, Koudsi H, Verschoore M, Schaefer H. Anthralin for psoriasis: short-contact anthralin therapy compared with topical steroid and conventional anthralin. J Am Acad Dermatol 1984;10:69-72.  Back to cited text no. 6
    
7.
Schaefer H. Short-contact therapy. Arch Dermatol 1985;121:1505-9.  Back to cited text no. 7
    
8.
Schaefer H, Farber EM, Goldberg L, Schalla W. Limited application period for dithranol in psoriasis − preliminary report on penetration and clinical efficacy. Br J Dermatol 1980;102:571-3.  Back to cited text no. 8
    
9.
Hartman M, Prins M, Swinkels OQ, Severens JL, De Boo T, Van Der Wilt GJ et al. Cost effectiveness analysis of a psoriasis care instruction programme with dithranol compared with UVB phototherapy and inpatient dithranol treatment. Br J Dermatol 2002;147:538-44.  Back to cited text no. 9
    
10.
Swinehart JM, Lowe NJ. UVABA therapy for psoriasis. Efficacy with shortened treatment times with the combined use of coal tar, anthralin, and metal halide ultraviolet machines. J Am Acad Dermatol 1991;24:594-7.  Back to cited text no. 10
    
11.
Ashton RE, Andre P, Lowe NJ, Whitefield M. Anthralin: historical and current perspectives. J Am Acad Dermatol 1983;9:173-92.  Back to cited text no. 11
    
12.
Hjorth N, Madsen K, Nørgaard M. Anthralin stick (Anthraderm) in the treatment of mosaic warts. Acta Derm Venereol 1986;66:181-2.  Back to cited text no. 12
    
13.
Rulo HF, van de Kerkhof PC. Treatment of inflammatory linear verrucous epidermal nevus. Dermatologica 1991;182:112-24.  Back to cited text no. 13
    
14.
de Mare S, van de Kerkhof PC, Happle R. Dithranol in the treatment of inflammatory linear verrucous epidermal nevus. Acta Derm Venereol 1989;69:77-80.  Back to cited text no. 14
    
15.
Silverman A, Menter A, Hairston JL. Tars and anthralins. Dermatol Clin 1995;13:817-33.  Back to cited text no. 15
    
16.
Swinkels OQ, Prins M, Tosserams EF, Gerritsen MJ, Van Der Valk PG, Van De Kerkhof PC. The influence of a topical corticosteroid on short-contact high-dose dithranol therapy. Br J Dermatol 2001;145:63-9  Back to cited text no. 16
    
17.
Dabas R, Janney MS, Subramaniyan R, Arora S, Lal VS, Donaparthi N. Use of over-the-counter topical medications in dermatophytosis: a cross-sectional, single-center, pilot study from a tertiary care hospital. Indian J Drugs Dermatol 2018;4:13-7.  Back to cited text no. 17
  [Full text]  
18.
Seville RH. Relapse rate of psoriasis worsened by adding steroids to a dithranol regime. Br J Dermatol 1976;95:643-6.  Back to cited text no. 18
    
19.
Lawrence CM, Shuster S. Mechanism of anthralin inflammation. Dissociation of response to clobetasol and indomethacin. Br J Dermatol 1985;113:107-15.  Back to cited text no. 19
    
20.
Lawrence CM, Shuster S. Mechanism of anthralin inflammation. Effect of pretreatment with glucocorticoids, anthralin and removal of stratum corneum. Br J Dermatol 1985;113:117-22.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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