Topical Nicotinamide in Treatment of DLE
Condition: Discoid Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Discoid
Study type: Interventional
Phase: Early Phase 1

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.
    

Intervention name(s): Nicotinamide Topical
Intervention type(s): Drug
Intervention description(s): Patients with discoid lupus erythematosus (face & scalp) will be given topical nicotinamide in two concentrations (2&4%) to apply twice daily for 12 consecutive weeks and then follow up.
Topical nicotinamide will be prepared in different forms (cream & gel).
Other intervention name(s): Topical treatment of skin lesions
Intervention MeSH terms: Niacinamide; Niacin; Nicotinic Acids
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment