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Topical Nicotinamide in Treatment of DLE

Early Phase 1
Completed
Conditions
Discoid Lupus Erythematosus
Interventions
Registration Number
NCT05362188
Lead Sponsor
Al-Azhar University
Brief Summary

Cutaneous lupus erythematosus (CLE) is lupus affecting the skin. In this autoimmune disease, the body's immune system attacks healthy skin. There are 3 main types: Acute cutaneous lupus, Subacute cutaneous lupus, and Chronic cutaneous lupus ("discoid lupus"). Lupus most often appears between the ages of 20 and 50 years; it affects women more than men, and it may happen more in patients with a family history of lupus or other autoimmune diseases.

Detailed Description

DLE is the most common form of chronic cutaneous erythematosus and can occur as a localized form (80%) with lesions on the face, ears, and scalp or as disseminated DLE (20%) with lesions above and below the neck. The disseminated form of DLE, especially when involving the trunk, is associated with an increased risk of progression to SLE. It is unusual for discoid lesions to be present below the neck without lesions also being present above the neck. Occasionally, discoid lesions develop on mucosal surfaces, including the lips, nasal mucosa, conjunctivae, and genital mucosa. Some patients with discoid lesions exhibit a photodistribution. Sun exposure seems to play a role in the development of lesions.

For discoid lupus erythematosus without associated SLE (CDLE), the evidence does not show whether circulating inflammatory cells and autoantibodies are involved in the pathogenesis, but it is evident that the cutaneous inflammatory infiltrates are dominated by Th1.

The first morphological sign of DLE is a well-defined, annular erythematous patch or plaque of varying size followed by follicular hyperkeratosis, which is adherent to the skin. By removing the adherent scale, follicle-sized keratotic spikes similar to carpet tacks can be seen ("carpet tack sign"). The lesions slowly expand with active inflammation and hyperpigmentation at the periphery leaving depressed central atrophy and scarring, telangiectasia, and hypopigmentation. DLE can progress to irreversible scarring alopecia on the scalp. Although uncommon, a squamous cell carcinoma can develop in a longstanding discoid lesion.

A biopsy from the lesion for routine histologic examination is usually diagnostic of DLE. Atrophic epidermis, keratotic plugging of the follicles, hydropic degeneration of the basal cells, and patchy perivascular and perifollicular lymphocytic infiltrate are characteristic.

Early treatment of discoid lupus lesions may lead to the total clearing of skin lesions, but treatment failure results in permanent scarring. Hair loss, depressed scars, and pigmentary changes are often disfiguring, particularly in darker-skinned people. Some general measures, such as sun avoidance and liberal application of sunscreen, are encouraged because cutaneous lesions are known to be exacerbated by sunlight. Smoking cessation is encouraged, as this can increase DLE disease activity.

While antimalarials such as hydroxychloroquine have been widely used as a first-line treatment for lupus-associated skin lesions, 30% of patients with lupus do not respond to this medication. Other available therapies such as corticosteroids and thalidomide can also be applied, however, their toxic side effects limit their clinical use. Recent studies by the investigators have shown that nicotinamide, a water-soluble vitamin whose side effects are considered minimal, can protect against skin lesions and autoantibody production. Thus it is hypothesized that nicotinamide treatment could be a novel therapy for lupus-associated skin lesions in patients with LE.

Nicotinamide is the amide form of vitamin B3 . It is the precursor of numerous reactions in the body including adenosine triphosphate (ATP) production and consequently can be used in many dermatological disorders.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
Inclusion Criteria
  • Age: between 18 years and 65 years old
  • Patients clinically and histopathologically newly diagnosed as DLE
  • Patients clinically and histopathologically diagnosed with cutaneous lupus erythematosus that has not responded to treatment with hydroxychloroquine(200-400mg/day) plus corticosteroid at a dosage less than the equivalent of (0.5mg/kg/day) for the preceding two months or a longer period
Exclusion Criteria
  • Age < 18 years old
  • Pregnant and lactating women
  • A history of treatments with multivitamins in the recent month
  • Soft tissue infection
  • Severe comorbidities including heart failure, respiratory failure
  • Acute severe infections such as cellulitis or a history of HBV or HCV

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboNicotinamide TopicalSubjects will receive only cream/gel base without API for control
Topical Nicotinamide 4%Nicotinamide Topicalwill receive topical nicotinamide 4%
Topical Nicotinamide 2%Nicotinamide Topicalwill receive topical nicotinamide 2%
Primary Outcome Measures
NameTimeMethod
Activity scorefrom base line ( visit 0 ) to 1 , 2 respectively

A change in discoid lupus erythematosus activity score

Severity indexfrom base line ( visit 0 ) to 1 , 2 respectively

A change in discoid lupus erythematosus severity index

Secondary Outcome Measures
NameTimeMethod
Response2 months

defined as \> 25% change in activity score at the end of treatment

The dermatology life Quality Index score2 months

A change in Dermatology life Quality Index score as it reflects the quality of life related to skin manifestations

Remarkable response2 months

defined as \> 50% change in activity score

Trial Locations

Locations (1)

AL-Azhar University Hospital

🇪🇬

Cairo, Egypt

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