Topical Cyclosporine Suspension for the Treatment of Brittle Nails
Condition: Brittle Nail Syndrome
MeSH terms: Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      Brittle nail syndrome (BNS) refers to nails that exhibit splitting, raggedness (fraying of
      the distal edge), and peeling (lamellar onychoschizia).(1) This is a common problem,
      affecting approximately 20% of women, with higher prevalence among the elderly.(2) A number
      of factors have been proposed as possible causes of nail brittleness, such as anemia, biotin
      deficiency, or cysteine deficiency. (3,4) However, most authors believe that brittle nails
      are usually caused by dehydration of the nail plate, either from repetitive cycles of
      hydration and dehydration related to hand washing or from exposure to dehydrating chemicals,
      such as those found in nail enamel and cuticle removers. (5,6) Inflammation of the nail as a
      potential contributing factor has never been studied.

      There are currently not consistently effective treatments for this condition. Restasis® is
      effective in treating keratoconjunctivitis sicca. This condition is characterized by the
      troublesome condition of dry eyes partially due to decreased tear production exacerbated by
      inflammation. The BNS manifests itself by nail plate dehydration. The two conditions have in
      common disruption of water balance which gives rise to problematic clinical disorders. The
      hypothesis is that a product which benefits tear production would also be effective for
      brittle nails which contain roughly 15% water.
    

Detailed description: 
      Brittle nail syndrome (BNS) is a heterogeneous abnormality, characterized by increased
      fragility of the nail plate. About 20% of the population is affected by brittle nails and
      women are affected twice as frequently as men. (2). The diagnostic criteria for brittle nails
      are not well defined but most authors agree in at least these 3 criteria: onychoschizia
      (lamellar splitting of the free edge and distal portion of the nail plate), onychorrhexis
      (longitudinal thickening and thinning or ridging of the nail plate) and fraying or raggedness
      of the distal edge causing transverse splitting.

      Although the cause of nail brittleness is unknown, most authors believe that it is caused by
      dehydration of the nail plate and that frequent cycles of hydration and dehydration as well
      as various mechanical and chemical insults increase the incidence of brittle nails. (7) The
      nail plate contains about 15% water and a very low lipid content so water permeation through
      the nail plate is high.(8) In fact, it has been demonstrated that the flux of water across
      the nail plate is 10 times more than the epidermis and 1000 times more permeable than the
      stratum corneum.(9) A recent report show that there was no significant difference in water
      content of brittle nails when compared to normal nails and suggested that nail plate water
      content is random and that nail plates are in a constant state of influx and efflux of water.
      (10) Keratoconjunctivitis sicca is a chronic, bilateral desiccation of the conjunctiva and
      cornea due to an inadequate tear film. There are two types: one caused by an inadequate tear
      volume and the other one caused by an accelerated tear evaporation due to poor tear quality
      (11). Restasis® (cyclosporine 0.05% topical emulsion) is effective in treating
      keratoconjunctivitis sicca.

      BNS and keratoconjunctivitis sicca have in common a disruption of water balance which gives
      rise to problematic clinical disorders. We hypothesize that a product which improves corneal
      dehydration would also be effective for brittle nails. Our rationale for using occlusion is
      that is has been shown that occluding the skin with a vapor-permeable membrane increases the
      water flux and the barrier function is recovered at a normal rate. (12) We also hypothesize
      that using Restasis® (cyclosporine 0.05% topical emulsion) or its vehicle (Refresh Dry Eye
      Therapy®) under occlusion with a finger cot will increase the nail plate hydration balance
      and as a consequence will improve nail brittleness. Topical cyclosporine has been shown to be
      safe in the treatment of other dermatological conditions such as nail psoriasis and oral
      lichen planus. (13,14) An investigator-blinded design will differentiate if the observed
      effects are caused by the active ingredient in Restasis® (cyclosporine 0.05% topical
      emulsion) or its vehicle (Refresh Dry Eye Therapy®).
    

Intervention name(s): topical cyclosporine ophthalmic suspension 0.05%; vehicle
Intervention type(s): Drug; Drug
Intervention description(s): apply 2 drops to 2 target fingernails under occlusion daily; apply 2 drops to 2 target fingernails under occlusion daily for 20 weeks
Other intervention name(s): Restasis; Refresh Dry Eye Therapy
Intervention MeSH terms: Cyclosporine; Cyclosporins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: brittle nail