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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 7  |  Issue : 2  |  Page : 60-66

Effective treatment option for lichen planus: Steroids or low molecular weight heparins?


1 Aesthetics Skin and Laser Clinic, Tirupathi, Andhra Pradesh, India
2 Department of Dermatology, Leprosy and Venerology, Apollo Institute of Medical Sciences and Research, Jubilee Hills, Hyderabad, Telangana, India

Date of Submission18-May-2020
Date of Decision20-Mar-2021
Date of Acceptance01-Sep-2021
Date of Web Publication14-Dec-2021

Correspondence Address:
Tina Priscilla
403, Supercorona Apartments, Near Shaikpet Dargah, OU Colony, Hyderabad 500008, Telangana.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdd.ijdd_31_20

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  Abstract 

Background: Data on safety and efficacy of low molecular weight heparin (LMWH) in lichen planus (LP) and comparison with oral corticosteroids (OCs) in Indian patients is limited. Aims: The aim of this article is to compare the clinical efficacy of LMWH and systemic corticosteroids in LP. Materials and Methods: This study was a single-center prospective comparative study. The patients received either LMWH subcutaneously (3 mg weekly for 6 weeks) or OC (20 mg/day for 6 weeks, tapered gradually). Results: Fifty patients were enrolled in the study, and 35 (70.0%) were females. Mean age of the study population was 35.46 years with age ranging between 21 and 40 years. Itching (92.0%) was a common symptom; generalized cutaneous lesions (90.0%) and involvement of mucous membrane were seen in 40%. Classical LP was common (56.0%). Early results were seen with OC (week 4) compared to LMWH (week 5); higher cure rate was seen with OC (89.47% vs. 76.0%) at week 6. There was no significant statistical difference (P > 0.05) in the therapeutic response between the study groups. No new lesions were noted in 23 and 13 patients treated with OC and LMWH, respectively. Relapse rate (33.33%) was higher in patients treated with LMWH (P < 0.05). Treatment with low-dose LMWH was associated with no side effects, whereas gastric irritation (42.1%) was the most common side effect followed by facial puffiness (31.57%) and acneiform eruptions (26.31%) with OC. The cost of treatment was more for LMWH compared with OC. Conclusion: Both treatment modalities were comparable in efficacy and tolerated well. LMWH had no adverse effect but had a high relapse rate. Therapy with OC is cost-effective.

Keywords: Cost-effective therapy, lichen planus, low molecular weight heparin, oral corticosteroids, relapse


How to cite this article:
Parlapalli N, Priscilla T. Effective treatment option for lichen planus: Steroids or low molecular weight heparins?. Indian J Drugs Dermatol 2021;7:60-6

How to cite this URL:
Parlapalli N, Priscilla T. Effective treatment option for lichen planus: Steroids or low molecular weight heparins?. Indian J Drugs Dermatol [serial online] 2021 [cited 2022 Jan 28];7:60-6. Available from: https://www.ijdd.in/text.asp?2021/7/2/60/332420




  Introduction Top


The treatment of lichen planus (LP) can be both challenging and discouraging for the patient and the physician. Variable course and self-limited duration of LP make adequate evaluation of therapy difficult.

Topical applications (corticosteroids, retinoids, tacrolimus, pimecrolimus, and cyclosporin) are the first option for simple LP and widely prescribed. Intra-lesion injection of corticosteroids is preferred in hypertrophic LP. Systemic use of various drugs effective in the management of LP includes corticosteroids, low molecular weight heparin (LMWH), dapsone, retinoids, antifungals (griseofulvin), and anti-malarial agents. Photochemotherapy, interferon α 2b, and biologics have also shown promising results. Surgical management, i.e., split thickness skin graft, cryosurgery, laser, surgical excision, and radiotherapy is reserved for those who are unresponsive to pharmacotherapy.

Currently, corticosteroids are the first line of drugs used in the treatment of LP. Depending on the extent of involvement and type of lesions, steroids can be used as topical, systemic, intra-lesional forms. Systemic corticosteroids are the mainstay of dermatologic therapy because of their potent immunosuppressive and anti-inflammatory properties.[1] But, their long-term usage is associated with adverse systemic effects.

LMWH at a dose of 3 mg/week subcutaneous injections may significantly improve the symptoms of pruritus and activity of LP.[2] Four to six injections of heparin induce complete remission of lesions.

LP is characterized by features of cell-mediated attack on the epidermis by activated T-lymphocytes. It has been suggested that an unknown antigen is being processed by Langerhans cells, which activate T-lymphocytes that subsequently destroy the basal layer. These lymphocytes produce an endoglycosidase (heparinase) which allows them to penetrate into the subendothelial basal lamina. Heparin inhibits T-lymphocyte heparinase, resulting in the prevention of T-cell hypersensitivity.[3]

There are limited reports on the clinical efficacy of LMWH in our population, comparison with that of corticosteroids. Moreover, safety is a concerning issue in addition to increasing cost of treatment. Corticosteroids are being preferred in developing and underdeveloped countries for the low cost and non-requirement of trained personnel. Hence, we studied the practical utility of LMWH and corticosteroids in the management of LP.


  Materials and Methods Top


This was a prospective, comparative study conducted by the Department of Dermatology of a referral tertiary care government hospital. This study was initiated after the approval by the Institutional Ethics Committee, and patients were screened only after obtaining the written informed consent. Comparing the clinical efficacy of low-dose LMWH and oral corticosteroids (OCs) on LP was the primary objective of the study. Comparison of safety profile, relapse rate, and cost of treatment were the secondary objectives. Patients with generalized cutaneous LP, mucosal LP, hypertrophic LP, follicular LP, and linear LP were included in this study.

Patient details including demography, symptoms and duration, treatment history, personal and family history were recorded on the preapproved proforma. A detailed clinical and dermatological examination was carried out. Clinical diagnosis of LP was confirmed by histopathological findings. Baseline investigations including hematological investigations, platelet count, bleeding time, clotting time, random blood glucose, liver function tests (serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin), test for syphilis (venereal disease research laboratory test), and urine examination (microscopy, albumin, sugar) were done by standard laboratory methods. Chest X-ray was done to rule out involvement of respiratory system.

Eligible patients were divided into two groups using the block randomization method. Group 1 received low-dose LMWH [ENOXAPARIN, subcutaneously (3 mg weekly for 6 weeks)] and group 2 received systemic corticosteroids (OC dose—20 mg/day for 6 weeks, tapered gradually over 6 weeks). Dosage of oral steroids was chosen based on the average body weight and to avoid systemic side effects of steroids. No other systemic or topical drugs were prescribed to the participants. Participants were followed up weekly for clinical evaluation of the lesions, grading the response of existing lesions, symptomatic relief, appearance of new lesions, and side effects if any during the study period.

Therapeutic response was graded on a scale of 5 [Table 1].[4]
Table 1: Disease response grading

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Statistical analysis

Data were captured on Microsoft Excel (2007) worksheets and analyzed using SAS software (version 9). Results were expressed as frequency, mean, %; the χ2 test was used for categorical variables.


  Results Top


Fifty eligible patients were enrolled in the study. There were 25 patients in each group with a mean±SD age of 35.46 years±10 (10–60 years). There were 35 (70.0%) females and 15 (30.0%) males. There were more females (n = 35, 70.0%, group 1 n = 18 and group 2 n = 17) than males (n = 15, 30.0%, group 1 n = 7 and group 2 n = 8). Most of the participants were agriculture laborers (n = 25, 50.0%, group 1 n=13, group 2 n = 12); there were housemaids (n = 4), homemakers (n = 7), farmers (n = 2), office clerk (n = 1), students (n = 6), shop owners (n = 1), fruit vendors (n = 2), beedi worker (n = 1), and coolie (n = 1).

Patients in the 31–40 years age group (n = 21, 42%) were the most affected, followed by those in 21–35 years (n = 11, 22%) [Figure 1]. Itching was seen in 46 (92.0%) and anemia in 20 (40.0%); involvement of mucous membrane was noted in 20 (40.0%).
Figure 1: Age distribution among the study population

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[Table 2] compares the demography and clinical presentation among the study groups.
Table 2: Comparison of demographic characteristics and clinical presentation among the study groups

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Classical LP with mucosal involvement was frequent (n = 29, 58%) followed by classical LP alone (n = 16, 32%). Two patients had ulcers [Table 3]. In group 1, 23 (23/25, 92.0%) had generalized cutaneous lesions; one each had generalized cutaneous LP with hypertrophic LP on the lower limb and hypertrophic LP alone, respectively. In group 2, 22 (22/25, 88.0%) had generalized cutaneous lesions; two had linear LP, and one had generalized cutaneous LP with follicular LP.
Table 3: Clinical presentation of LP among the study population

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Early results were seen with OC (group 2), i.e., in week 4 and the cure rate was 89.47%. With low-dose LMWH (group 1), cure started in week 5 and the cure rate was 76%. There were six patients in group 2 who were lost to follow up. There was no significant statistical difference (P > 0.05) in the therapeutic response between the study groups.

Appearance of no new lesions was noted in 23 in group 2 and the remaining two had reappearance at week 2. In group 1, 12 had appearance of new lesions of whom two patients had new lesions at week 1, six at week 2, one at weeks 2, 3, 5, and 6; 13 never had appearance of new lesions.

[Table 4] provides the details of the therapeutic response among the study population, and [Table 5] compares the response between the two study groups. Figures [2, 3] and [4, 5] represent pre- and post-treatment with low molecular weight heparin and oral steroids, respectively. There was no statistically significant difference between the study groups in the therapeutic response.
Table 4: Response to therapy

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Table 5: Comparison of therapeutic response between the study groups

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Figures 2 and 3: Pre- and post-treatment with LMWH

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Figures 4 and 5: Pre- and post-treatment with oral steroids

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In the first follow-up, in group 1, there was no significant difference in the relapse rate. Relapse was noted in eight patients (group I, 7); 28 had no relapse (14 in each group) and eight (4 in each group) were lost to follow-up in the first follow-up. Data of six were unavailable. In group 2, only one patient had relapse; four were lost to follow-up, and 12 had no relapse.

During the next follow-ups, no relapse after 2 months was noted in 18 (group 2, 14), after 3 months in three (group 1, n = 02), after 6 months in four (all in group 2); four were lost to follow-up in group 1 and 14 (all in group 1) had no relapse. The data of seven were unavailable.

There was no side effect encountered with low-dose LMWH, whereas gastric irritation (n = 08, 42.1%) was the most common side effect followed by facial puffiness (n = 06, 31.57%) with OCs. Gastric irritation was managed with antacids. Acneiform eruptions were seen in five (26.31%) patients.

The relapse rate was high (n = 07, 33.33%) with LMWH compared to OCs (n = 01, 6.66%) and was statistically significant (P < 0.05) [Table 6].
Table 6: Relapse rate in the study groups

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The cost of treatment was more for LMWH when compared with OCs [Table 7]. None of the patients in both the groups received topical drugs.
Table 7: Medication cost for treating LP

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Safety investigations

There were no laboratory abnormalities in the study population during the study period.


  Discussion Top


Although LP is a relatively common dermatological condition, its exact epidemiological data remain unknown; available data indicate an overall prevalence of 1% with a global estimate of 0.22–5%.[5] An incidence of 0.8% was reported from Delhi, India.[6]

In Western countries, those aged between 30 and 60 years are more affected (≈2/3) whereas in India, it is more prevalent between 20 and 40 years.[6] In our study, 64% of the participants were in 20–40 years age group.

In India, LP is more common among men, whereas in the west, slight female preponderance is reported.[7] There are reports of equal incidence in both genders.[8],[9] We report a female preponderance (70%) in our study. Classical LP with mucosal involvement is the most common, i.e., 58% (29 cases), followed by the classical LP alone without mucosal involvement, i.e., 32% (16 cases).[10] In Indian series, the skin alone was affected in 70%, skin and mucous membranes in 23%, and mucous membranes alone in 6%.[10]

Various treatment options are tried in the management of LP including corticosteroids, antihistamines, retinoids,[11] extracorporeal photochemotherapy,[12] and other miscellaneous agents such as sulfasalazine[13] and calcineurin inhibitors.[14] None of these has proved superior making the choice difficult for the physician, and need for evidence for effective therapy. Corticosteroids either topical or systemic have retained their place in therapy as the first choice since long.[15],[16] Enoxaparin has emerged a promising candidate among all. Hodak et al.[2] were the first to report its use in LP. Low dose heparin (enoxaparin) at a dose of 3 mg subcutaneously once a week resulted in complete cure in 80% (8/10) of the patients; seven patients remained in remission from five to 18 months. Relapse was noted in 40% of the patients at 6-month follow-up. This study showed an early response in 2 weeks of initiating therapy. In a similar study, 72% (13/18) of the patients showed complete remission and marked improvement.[17] It has a proven effect in Indian patients as well. Complete regression of lesions with residual post-inflammatory hyperpigmentation was seen in 81% of the patients treated with enoxaparin 5 mg subcutaneously once a week.[18] There was no side effect reported from any of these studies. But the available data are limited with one randomized controlled trial and 12 non-randomized studies.[2],[3],[17],[19],[20],[21],[22],[23],[24] Enoxaparin was reported to be effective in those who were unresponsive to OCs.[23],[24] In all these studies, enoxaparin was used at a dose of 3 mg, subcutaneously, once a week. Iraji et al.[25] used 5 mg once a week (maximum of 8 weeks) in 25 patients with disseminated LP; complete remission in 32% and partial improvement in 40% of their study population were seen. No improvement was seen in seven. Only one patient had a rash of new lesion at the site of injection. Lunge et al.[26] used a dose of 5 mg once a week for a longer period (16–24 weeks) in 20 patients with generalized LP. There was complete remission in 65%; relapse seen in the remaining was due to discontinuation of the drug. However, negative reports on enoxaparin cast a doubt on its efficacy in the clinical practice.[27],[28] These studies also noted adverse effects. These inconsistent reports indicate the need for more evidence.

We administered LMWH (enoxaparin) at a dose of 3 mg subcutaneously weekly for 6 weeks. At week 5, 12% of the patients responded to therapy and 64% of the patients responded at week 6. All had a post-inflammatory hyperpigmentation. About 24% of patients (six cases) did not show any response. No side effects were encountered throughout the course of treatment. Twenty-one patients were followed up to 6 months and four were lost to follow-up. The relapse rate with low-dose LMWH during this period of 6-month follow-up was 33.33% (7/21).

Of the 25 patients treated with systemic corticosteroids, six were defaulters. Of the 19 cases, 15.78% responded in 4 weeks, suggesting an early response. A higher percentage of patients (57.89%) responded in 5 weeks. At week 6, 15.78% of the patients responded. Totally, 89.47% of the patients responded with systemic corticosteroids, leaving post-inflammatory hyperpigmentation. Two patients did not show any response. Facial puffiness (31.57%), gastric irritation (42.1%), and acneiform eruptions (26.31%) were the side effects noted. Of the 19 patients, 15 were followed up to 6 months; only one had relapse with OCs at 6-month follow-up.

Corticosteroids have been traditionally gold standard for the treatment of LP.[29],[30],[31] OCs are highly effective but the long-term use may result in serious side effects. Although the side effects were not encountered with low-dose LMWH, complete clinical cure is achieved late. Poor cost-effectiveness and high relapse rate (33.33%) make LMWH a second line of drug in the management of LP. Inexpensive corticosteroids are the treatment of choice for LP. Side effects such as gastric irritation, facial puffiness, and acneiform eruptions encountered with corticosteroids can be managed symptomatically. Hence, low-dose LMWH constitutes an alternative for the treatment of LP.


  Conclusion Top


Both treatment modalities are comparable in efficacy and tolerated well by the study population. Common adverse effects of corticosteroids included gastritis, facial puffiness, and acne. There was no adverse effect reported with LMWH but had a high relapse rate. Lost to follow-up is an issue that needs to be addressed. Therapy with OCs is cost-effective.

Author contribution

Both authors contributed to the concept and conduct of the study. Dr Neelima prepared the study protocol and proforma, reviewed the manuscript, and approved the final version; Dr Tina conducted the study, interpreted the statistical analysis, prepared, and edited the manuscript.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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[PUBMED]  [Full text]  
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    Figures

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

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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