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ORIGINAL ARTICLE
Year : 2021  |  Volume : 12  |  Issue : 1  |  Page : 21-25

Comparative evaluation of steroid sensitivity in various dermatoses with control group through histopathological examination and patch testing


1 Department of Dermatology, Lokmanya Tilak Municipal General Hospital, Navi Mumbai, Maharashtra, India
2 Department of Dermatology, MGM Medical College and Hospital, Navi Mumbai, Maharashtra, India

Date of Submission18-May-2021
Date of Acceptance16-Jul-2021
Date of Web Publication03-Sep-2021

Correspondence Address:
Dr. Shylaja Someshwar
Department of Dermatology, MGM Medical College and Hospital, Kamothe, Navi Mumbai- 410209, Maharashtra
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mjmsr.mjmsr_18_21

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  Abstract 


Background: Topical corticosteroids are widely used for treating various dermatoses. People have been self-medicating them for fungal infections, pigmentary disorders, and for many other dermatoses. This overzealous and irrational use of corticosteroid makes individuals susceptible for its adverse effects. Aim: The aim of this study was to evaluate steroid sensitivity in various dermatoses. Materials and Methods: Patch testing with Indian standard series and corticosteroid series was performed in sixty subjects where thirty patients were cases and thirty were controls. Histopathological examination and As it is (ASIS) were done only for the case group. Patches were applied on the back for 48 h and reading was done on day 2, day 4, and day 7 according to the International Contact Dermatitis Research group grading. Results: The maximum cases were in the age group of 20–30 years (33.3%) while 31–40 years was the most common age range (50%) among controls. Among the case group, 60% were male and 40% were female. Maximum patients affected in the case group were homemakers (36.7%) followed by laborers (13.3%). The case group showed 16.7% positive patch test reactions while none were positive in the control group. Thiomersal was positive in 13.3% of cases and neomycin in 3.3% of cases. ASIS was negative in all cases. Thiomersal is commonly used as a preservative in topical medicaments, cosmetics, and vaccines. Conclusions: Steroid sensitivity is hard to diagnose clinically, thereby causing difficulty in managing such cases. Patch test is a noninvasive gold standard procedure without major adverse effects and helps in treating the dermatoses with appropriate class of corticosteroid by avoiding the suspected allergen.

Keywords: Corticosteroid series, patch testing, steroid sensitivity


How to cite this article:
Lodha A, Someshwar S. Comparative evaluation of steroid sensitivity in various dermatoses with control group through histopathological examination and patch testing. Muller J Med Sci Res 2021;12:21-5

How to cite this URL:
Lodha A, Someshwar S. Comparative evaluation of steroid sensitivity in various dermatoses with control group through histopathological examination and patch testing. Muller J Med Sci Res [serial online] 2021 [cited 2021 Nov 30];12:21-5. Available from: https://www.mjmsr.net/text.asp?2021/12/1/21/325477




  Introduction Top


Topical corticosteroids are the most commonly prescribed drugs in dermatology which are available over-the-counter (OTC) at a low price in India which has led to its misuse. People have been self-medicating them for fungal infections, pigmentary disorders, and for many other dermatoses. Topical corticosteroids are also used as a prescribed drug which patients may overuse or use them without any supervision; such individuals are susceptible for its adverse effects. The prevalence rate of allergic contact dermatitis by topical corticosteroid medicaments can be up to 5%.[1] Contact sensitization can be due to the corticosteroid itself or other ingredients such as vehicles or preservatives. The degradation products of corticosteroids interact with arginine causing sensitization and leading to allergic reaction.[2] Patch test has been used as a gold standard diagnostic tool for identification of allergens. The principle of patch test is that the primed antigen specific to T-lymphocytes is present in the sensitized individuals, and therefore, when standard concentration of the antigen is applied on normal skin, it would also produce a similar reaction.[3] Hence, determining the cause has helped people to improve their quality of life and reduce the recurrence by avoiding the contact to allergen. Contact allergy to topical corticosteroids is hard to diagnose clinically leading to therapeutic challenges. Hence, patch testing must be done to increase the detection of contact allergy. It should be routinely performed in patients with chronic dermatoses and in patients with long-term use of topical corticosteroids.[4] Contact allergy can be suspected in patients who have failed to show the response, or there is an unexplained flare-up of the condition. Standard allergens and corticosteroids may help in determining the causative allergen. However, patch testing with patients' own products (ASIS) is also important because many of the allergens are not available in the commercially available standard series and also consumers are exposed to new allergens daily due to constant change in environment.

Aim

The aim of this study was to evaluate steroid sensitivity in various dermatoses.


  Materials and Methods Top


A case–control prospective study was conducted in the outpatient department of dermatology in a tertiary care hospital in Navi Mumbai. A total of sixty subjects were enrolled in the study, with thirty patients in the case group and thirty in the control group. Patients with a history of topical use of steroids for more than 6 weeks or intermittent use for at least 6 months for any dermatoses were included in the case group. These patients underwent skin biopsy under aseptic precautions for histopathological examination. Patients on immunosuppressant drugs, pregnant or lactating women, and patients under 18 years of age were excluded from the study. The test was not performed in active dermatitis.

Method of patch test

Patch test was performed in both the case and control groups; herein, extended version of Indian standard series (ISS) of 56 allergens was obtained from the manufacturer Systopic laboratories Ltd. and corticosteroid series of 13 allergens imported from Chemotechnique Diagnostics, Sweden. ASIS patch testing was done in the case group with patients who owned and used steroid content creams/ointments. The allergens were applied in the readymade aluminum Finn chambers on Scanpor tape obtained directly from the manufacturer and were placed on the back. If the back was hairy, shaving was done prior. This was then restrengthened by applying Scanpor tape. The patients were instructed not to shower, get the back wet, or engage in sports while the patches were in place.

Patch was removed after 48 h that is on the 2nd day, and test readings were marked with highlighter pen after 1 h of removal. Patients were followed up on the 4th day and 7th day to look for delayed reaction. Readings were done according to scoring system that is International Contact Dermatitis Research Group guidelines [Table 1].
Table 1: International Contact Dermatitis Research Group grading

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Statistical analysis

All data collected were entered in Microsoft Excel spreadsheet and then transferred to SPSS software version 17 for analysis. Qualitative data were presented as frequency and percentages and analyzed using Chi-square test and Fisher's exact test wherever applicable. Quantitative data were presented as mean and SD and compared by t-test. P <0.05 was taken as a level of significance.


  Results Top


The maximum patients among the case group were aged between 20 and 30 years (33.3%) while in the control group were 31–40 years (50%). Among the 30 cases, 18 patients (60%) were male and 12 (40%) were female. The male-to-female ratio in the case group was 1.5:1. The most common occupation both in cases and controls was homemakers (36.7% in cases and 43.3% in controls) followed by laborers (13.3% each in cases and controls). The most commonly affected site was the feet (36.7%) followed by hands (20.0%) while the face (10%) was the least frequently affected. Maximum patients were affected by the disease for <20 months.

It was observed that maximum cases had applied clobetasol propionate (40%) followed by halobetasol propionate (20%), mometasone furoate, and beclometasone dipropionate (16.7% each). The least common application was fluocinolone acetonide and betamethasone valerate at 3.3% each. It was observed that 56.7% of the cases applied topical medicaments for over 7–12 months whereas a mere 3.3% applied for more than 24 months.

[Figure 1] shows that 36.7% of the cases were clinically diagnosed with psoriasis followed by 23.3% with eczema. Maximum cases 33.3% were diagnosed with psoriasis through histopathology while 26.7% of the cases were nonconclusive.
Figure 1: Distribution of cases according to clinical diagnosis

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Out of total cases, 20% were tested positive on day 2 and only 10% were positive on day 4 and 7 with average 16.7% of patients showing positive results. 16.7% of the cases were lost to follow-up and 66.7% were tested negative.

On performing extended version of ISS, out of thirty patients in the case group, five were positive for at least one allergen and twenty were negative. Five patients were lost to follow-up and did not complete assessment until 7 days. Four patients (13.3%) tested positive for thiomersal and one (3.3%) for neomycin [Table 2]. Among the controls, all patients who completed the follow-up were negative. Four (13.3%) were lost to follow-up. In the corticosteroid series, none of the patients tested positive in cases or control group.
Table 2: Positive results of patch test among cases

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[Table 3] shows histopathological correlation with Patch test results. Histopathology confirmed 10 psoriasis patients out of which 3 showed positive patch test reaction. Out these 3 patients, 2 of them had positive reaction on day 4 and day 7 as well.
Table 3: Distribution of cases and positive results of patch test according to histopathology

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Maximum patients who tested positive belong to 20–30 years and 41–50 years of age group. Out of five positively tested cases, four were female and one was male. The disease affected three cases for 21–40 months and two cases for <20 months among the positive cases.

Out of these positive cases, two were clinically diagnosed as psoriasis. Steroid-induced dermatitis, Lichen simplex chronicus and eczema were clinically diagnosed in one case each. According to histopathology, three of the positive cases were psoriasis, one was steroid-damaged skin, and one was eczema.

Fisher's exact test was used to compare the results of ISS in the case and control groups. A significant difference was seen between both the groups (Fisher's exact test statistic value 0.0226; P < 0.05). There was no significant difference in the results of corticosteroid series in both the groups.


  Discussion Top


Corticosteroid-containing double- or triple-combination medicaments are very common and easily available in India. They are widely used as an OTC drug and as a prescribed drug for treating various inflammatory dermatoses. This misuse has led to various adverse effects which drew our attention to conduct a study.

Allergic contact dermatitis caused by topical corticosteroid is troublesome and difficult to diagnose condition as it produces the very feature of the dermatoses that they are used to treat. It should be considered in all the patients who have used them for prolonged duration. Patients with long-standing or recurrent dermatitis-like hand and foot dermatitis, atopic dermatitis, and stasis dermatitis have maximum chances to develop steroid allergy.[5] Ghosh noted that steroid contact dermatitis can also occur in patients suffering from psoriasis, especially of palmoplantar variant. This is because there can be impaired epidermal barrier function and also use of various topical preparations.[6] To determine the exact cause of allergic contact dermatitis, patch testing can be done and is considered to be the conclusive test.

In 1989, Coopman et al. classified corticosteroids into four groups according to the structure as Groups A, B, C, and D.[7] Later, Goosens further divided Group D into Groups D1 and D2. These groups were determined according to substitutions done on the corticosteroid structure. Sensitization may vary among the groups. Group C and D1 corticosteroids seem to be less allergenic.[8] In corticosteroid patch testing, a specific compound is used to screen for class-specific reactions. When patch tests show allergy to a specific topical corticosteroid, it is likely that the patient will also be allergic to others in the same class. Therefore, the above classification can help to avoid the use of similar molecule and gives a better understanding of possible cross-reactions.

A total of sixty subjects who fulfilled the inclusion criteria were enrolled in this study, of which thirty were cases and the other thirty were controls. Patch test was done in all sixty subjects with extended version of ISS, corticosteroid series, while ASIS was used only in the case group.

Sahu et al.[1] noted that 47.4 years was the mean age of the studied population whereas 37.5 years was the mean age among our case group.

In our study, out of 30 cases, 18 patients (60%) were male and 12 patients (40%) were female. Male predominance was also seen in a study by Sahu et al.[1] where 71% of the study populations were male and 29% were female.

Sahu et al.[1] noted that the most commonly affected population were office workers (27%) followed by farmers (25%), whereas, in our study, homemakers (36.7%) were the most commonly affected followed by laborers (13.3%).

Baeck et al.[5] showed that homemaker (18%) was the most frequent occupation that tested positive to corticosteroid patch test which was followed by office work (17%). These findings were incomparable to our study as there was no positive reaction in corticosteroid series.

In a study conducted by Kot et al.,[9] they noted that 88.1% of the patients experienced cutaneous lesions on the hands followed by 41.3% on the lower legs and 31.7% on the face. These findings were nearly in accordance with our study where feet (36.7%) were most commonly affected followed by hands (20.0%) while the face (10%) was the least common site.

Kot et al.[9] observed that the duration of the disease ranged from 2 months to 42 years, with a mean duration of 82.8 months, while the disease duration in our study ranged from 7 months to 10 years with maximum <20 months of duration. Age and sex play a minor role in sensitization and elicitation in patch testing.

We observed that maximum cases had applied clobetasol propionate (40%) and halobetasol propionate (20%) whereas the least common applications were of fluocinolone acetonide (3.3%) and betamethasone valerate (3.3%). Clobetasol propionate and halobetasol propionate are superpotent drugs that comprised maximum steroidal application in this study. About 56.7% of the cases applied these topical medicaments for over 7–12-month duration.

A study conducted by Dooms-Goossens and Morren,[10] observed that 2.6% of the patients had positive corticosteroid patch test while another study by Keegel et al.[11] showed a rate of 0.52% positive corticosteroid allergic dermatitis. This was discordant with our study as there was no positive reaction in corticosteroid patch test. Lutz et al.[12] stated that false-negative results can occur due to inherent property of corticosteroid which creates a problem in reading corticosteroid patch test.

Kot et al.[13] performed patch test in 126 patients with the clinical diagnosis of contact eczema with 28 European baseline series allergens and 8 corticosteroid allergens. In total, 65 patients (51.6%) demonstrated an allergic reaction to at least one European baseline series allergen and 22 patients (17.4%) to at least one corticosteroid. The most common allergens giving positive results were nickel sulfate (26.2%), cobalt chloride (15.1%), budesonide (14.3%), potassium dichromate (13.5%), and Myroxylon pereirae resin (11.9%).

Kot et al.[14] conducted patch test on a total of 39 patients with clinical diagnosis of atopic dermatitis during remission. Nineteen (48%) patients had an allergic reaction to at least one European standard series allergen, and five (12.8%) patients had an allergic reaction to at least one corticosteroid. The most common allergens giving positive results were nickel sulfate (28.2%), potassium dichromate (20.5%), cobalt chloride (12.8%), and phenylenediamine, budesonide, betamethasone, clobetasol, and dexamethasone (7.7% each).

Sarwar et al.[15] conducted a similar study on 105 patients in which allergic reactions to European standard series allergens were seen in 51 (48.6%) patients and allergic reactions to corticosteroid series were seen in 12 (11.4%) patients. Common allergens detected with European standard series were potassium dichromate (21%), cobalt chloride (12%), and nickel sulfate (12%). Common allergens detected with corticosteroid series were tixocortol-21-pivalate (8.6%) and hydrocortisone-17-butyrate (4.76%). Similarly, we observed that extended version of ISS had a maximum positive reaction, thiomersal being positive in four cases and neomycin in one. No one tested positive in corticosteroid series. There was a low frequency of sensitivity to allergens. Thiomersal is used as a preservative in some cosmetics, ophthalmic and otolaryngology medication, vaccines, antitoxins, and topical steroid preparations.[16] Neomycin is a common ingredient present in triple-combination medicaments. Once an allergen is identified, it is the dermatologist's task to advise the patients and provide a list of the products that have to be avoided. In our study, we found that a significant number of patients using topical medicaments had an allergic reaction to other ingredients as compared to the control group.

Further research on standard series and corticosteroid series is required with large sample size.

Limitations of the study

The number of the cases enrolled was small and thereby further studies on a larger scale are necessary. There is a need for more studies which test standard series in addition to steroid series to understand the pattern of sensitivity.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sahu U, Handa S, De D. Contact sensitivity to topical corticosteroids in India. Indian J Dermatol Venereol Leprol 2016;82:184-6.  Back to cited text no. 1
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2.
Wilkinson SM, Jones MF. Corticosteroid usage and binding to arginine: Determinants of corticosteroid hypersensitivity. Br J Dermatol 1996;135:225-30.  Back to cited text no. 2
    
3.
Mowad CM, Marks JM. Allergic contact dermatitis. In: Bolognia J, Jorizzo J, Schaffer J, editors. Dermatology. 3rd ed. Philadelphia: Elsevier Saunders; 2012. p. 233-48.  Back to cited text no. 3
    
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Browne F, Wilkinson SM. Effective prescribing in steroid allergy: Controversies and cross-reactions. Clin Dermatol 2011;29:287-94.  Back to cited text no. 4
    
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Baeck M, Marot L, Nicolas JF, Pilette C, Tennstedt D, Goossens A. Allergic hypersensitivity to topical and systemic corticosteroids: A review. Allergy 2009;64:978-94.  Back to cited text no. 5
    
6.
Ghosh S. Patch testing: Broadened spectrum of indications. Indian J Dermatol 2006;51:283-5.  Back to cited text no. 6
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Coopman S, Degreef H, Dooms-Goossens A. Identification of cross-reaction patterns in allergic contact dermatitis from topical corticosteroids. Br J Dermatol 1989;121:27-34.  Back to cited text no. 7
    
8.
Pratt MD, Mufti A, Lipson J, Warshaw EM, Maibach HI, Taylor JS, et al. Patch test reactions to corticosteroids: Retrospective analysis from the north american contact dermatitis group 2007-2014. Dermatitis 2017;28:58-63.  Back to cited text no. 8
    
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Kot M, Bogaczewicz J, Kręcisz B, Woźniacka A. Contact allergy in the population of patients with chronic inflammatory dermatoses and contact hypersensitivity to corticosteroids. Postepy Dermatol Alergol 2017;34:253-9.  Back to cited text no. 9
    
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Dooms-Goossens A, Morren M. Results of routine patch testing with corticosteroid series in 2073 patients. Contact Dermatitis 1992;26:182-91.  Back to cited text no. 10
    
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Keegel T, Saunders H, Milne R, Sajjachareonpong P, Fletcher A, Nixon R. Topical corticosteroid allergy in an urban Australian centre. Contact Dermatitis 2004;50:6-14.  Back to cited text no. 11
    
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Lutz ME, el-Azhary RA. Allergic contact dermatitis due to topical application of corticosteroids: Review and clinical implications. Mayo Clin Proc 1997;72:1141-4.  Back to cited text no. 12
    
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Kot M, Bogaczewicz J, Kręcisz B, Woźniacka A. Contact hypersensitivity to european baseline series and corticosteroid series haptens in a population of adult patients with contact eczema. Acta Dermatovenerol Croat 2016;24:29-36.  Back to cited text no. 13
    
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Kot M, Bogaczewicz J, Krecisz B, Wozniacka A. Contact hypersensitivity to haptens of the European standard series and corticosteroid series in the population of adolescents and adults with atopic dermatitis. Dermatitis 2014;25:72-6.  Back to cited text no. 14
    
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Sarwar U, Asad F, Rani Z, Kurshid K, Pal SS. Frequency of allergic contact dermatitis in hand eczema patients with European standard and corticosteroid series. J Pak Assoc Dermatol 2013;23:289-94.  Back to cited text no. 15
    
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Wattanakrai P, Rajatanavin N. Thimerosal allergy and clinical relevance in Thailand. J Med Assoc Thai 2007;90:1775-9.  Back to cited text no. 16
    


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