Brief Overview of Current Therapeutic Considerations in Cutaneous Lupus Erythematosus

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Brief Overview of Current Therapeutic Considerations in Cutaneous Lupus Erythematosus
Morayo Adisa, MD

Cutaneous lupus erythematosus (CLE) encompasses the group of autoimmune connective tissue disorders affecting the skin which may be associated with systemic lupus erythematosus (SLE) to varying degrees. The most used classification of CLE is that of Dr. James Gilliam and Dr. Richard Sontheimer that divide the cutaneous lesions into specific and those that are not specific based on the presence of absences of interface dermatitis on histopathology. ACLE and the nonspecific variants have the strongest association with systemic disease.

The LE-specifics skin lesions and their sub classifications are:

  1. Acute cutaneous LE (ACLE):
    • Malar erythema
    • Photo distributed erythema
  2. Subacute cutaneous lupus erythematosus (SCLE):
    • Psoriasiform, annular/polycyclic
    • Neonatal
  3. Chronic cutaneous lupus erythematosus (CCLE):
    • Discoid LE (DLE): Localized, generalized, hypertrophic
    • Lupus panniculitis
    • Tumid LE
  4. Other cutaneous lupus erythematosus 
    • Bullous lupus erythematosus


The LE- nonspecific skin lesions are:

  1. Diffuse non-scarring alopecia
  2. Vascular lesions: Raynaud phenomenon, livedo reticularis, palmar erythema, nail fold telangiectasia
  3. Vasculitis: Urticarial vasculitis, small vessel vasculitis, Polyarteritis nodosa-like lesions and Ulcerations


Treatment of CLE

  • Sun avoidance, sunscreens, sun protective clothing
    • For the sunscreens/sunblock ensure that the right amount is applied and also re-apply during the day
  • Smoking cessation
    • Tobacco smoke lowers risk of long-term remission
    • Decreases efficacy of systemic treatment
    • Increase severity of disease 
  • Vitamin D implementation
  • Cessation or avoidance of photosensitizers
  • Topical niacinamide (Nicotinamide) in 4% or 2% twice daily dosing have been reported as an effective treatment for discoid lupus erythematosus (DLE) 
  • Corticosteroids – Systemic and Topical
    • Topical corticosteroids are first line of treatment for localized and widespread disease
    • Systemic corticosteroids are first line for highly active and/or severe disease
  • Calcineurin inhibitors: pimecrolimus, tacrolimus 
  • Topical retinoids
    • Second-line treatment in verrucous LE and other hyperkeratotic lesions
    • Consideration for use in disease refractory to topical corticosteroids or calcineurin inhibitors
  • Antimalarials: Hydroxychloroquine (HCQ), Chloroquine (CQ) and Quinacrine
    • First-line and long-term systemic treatment in all CLE patients with severe and/or widespread skin lesions, particularly those with a high risk of scarring and/or the development of systemic disease
    • HCQ dosing calculated on body weight with a maximum daily dose of 5 mg/kg of real bodyweight
    • 55% response rate to HCQ in a cohort study
    • 66% of HCQ-refractory patients responded to addition of quinacrine to HCQ
    • Avoid combination of HCQ and CQ because of the risk of irreversible retinopathy
  • Immunosuppressives and immunomodulators: methotrexate (MTX), dapsone, systemic retinoids, mycophenolate mofetil and thalidomide with its derivatives lenalidomide and Iberdomide
    • 50% of patients responded when treated with immunosuppressives.
    • Methotrexate and mycophenolate mofetil more effective than azathioprine
  • B cell- targeted therapies (Biologics): Rituximab, Belimumab
    • Rituximab is a monoclonal antibody directed against the CD20 antigen, leading to B cell depletion
      • According to current SLE guidelines, in refractory SLE or in case of intolerance/contraindications to standard immunosuppressive agents
      • Effective in treating severe CLE in some patients with systemic disease, especially those with acute, non-specific types, Bullous lupus and lupus erythematosus panniculitis
    • Belimumab is a monoclonal antibody that reduces B lymphocyte survival by blocking the binding of soluble human B lymphocyte stimulator (BLyS) to its B cell receptors
      • Stimulates B lymphocytes to develop into mature B-cells
      • Approved for SLE and Lupus Nephritis
      • Best used for widespread, refractory CLE lesions in patients with active SLE
      • Beneficial in mild persistent activity and phototypes IV to VI
  • Intravenous immunoglobulins:
    • Response in refractory CLE range from partial to almost complete resolution
  • Janus kinase inhibitors (Ruxolitinib or baricitinib (JAK1/JAK2 inhibitors) and tofacitinib (primarily JAK3 inhibitor)
    • Reported to clear recalcitrant CLE lesions
    • Baricitinib showed efficacy in papulosquamous rash in SLE, SCLE and no further progression of the FFA
    • Ruxolitinib, baricitinib and tofacitinib have been trialed as therapeutic options for familial chilblain LE
    • Successful response reported to tocilizumab in non-familial refractory chilblain LE
  • Anifrolumab
    • Approved In 2021 by the Food and Drug Administration-approval for the treatment of the treatment of autoimmune disorders, including moderate to severe systemic lupus erythematosus (SLE) and lupus nephritis
    • Monoclonal antibody that selectively binds and inhibits the type 1 interferon- α receptor 1 (IFNAR1)

    • Most common adverse events:
      1. upper respiratory tract infections (34%)
      2. infusion-related reactions (9.4%)
      3. herpes zoster (6.1%)
      4. cough (5.0%) 
      5. respiratory tract infection (3.3%)
      6. hypersensitivity reaction (2.8%)
    • Great for the management of refractory disease (difficulty achieving adequate disease control while on standard of care treatments- antimalarials, disease modifying agents, and biologics)
      • Has been reported as an effective treatment choice for patients with refractory CLE and those who continue to use tobacco or other substances during treatment



References:

  1. Fredeau L, Courvoisier DS, Ait Mehdi R, Ingen-Housz-Oro S, Mahe E, Costedoat-Chalumeau N, Arnaud L, Francès C, Mathian A, Jachiet M, Amoura Z, Bouaziz JD, Chasset F; EMSED study group. Risk factors of progression from discoid lupus to severe systemic lupus erythematosus: a registry-based cohort study of 164 patients. J Am Acad Dermatol. 2022 Sep 23:S0190-9622(22)02771-2. doi: 10.1016/j.jaad.2022.09.028. Epub ahead of print. PMID: 36156304.

  2. Wieczorek IT, Propert KJ, Okawa J, Werth VP. Systemic symptoms in the progression of cutaneous to systemic lupus erythematosus. JAMA Dermatol. 2014 Mar;150(3):291-6. doi: 10.1001/jamadermatol.2013.9026. PMID: 24477339.

  3. Nouh AH, Elshahid AR, Kadah AS, Zeyada YA. Topical niacinamide (Nicotinamide) treatment for discoid lupus erythematosus (DLE): A prospective pilot study. J Cosmet Dermatol. 2023 Jan 22. doi: 10.1111/jocd.15628. Epub ahead of print. PMID: 36683259.

  4. Verdelli A, Corrà A, Mariotti EB, Aimo C, Ruffo di Calabria V, Volpi W, Quintarelli L, Caproni M. An update on the management of refractory cutaneous lupus erythematosus. Front Med (Lausanne). 2022 Sep 23;9:941003. doi: 10.3389/fmed.2022.941003. PMID: 36213629; PMCID: PMC9537468.
     
  5. Blum FR, Sampath AJ, Foulke GT. Anifrolumab for treatment of refractory cutaneous lupus erythematosus. Clin Exp Dermatol. 2022 Nov;47(11):1998-2001. doi: 10.1111/ced.15335. Epub 2022 Aug 26. PMID: 35844070.
     
  6. Shope C, Andrews L, Cunningham M, Connett J. A case of Rowell syndrome with excellent improvement following anifrolumab. JAAD Case Rep. 2022 Nov 13;31:27-30. doi: 10.1016/j.jdcr.2022.11.008. PMID: 36478979; PMCID: PMC9720243.
     
  7. Gilliam JN, Sontheimer RD. Distinctive cutaneous subsets in the spectrum of lupus erythematosus. J Am Acad Dermatol. 1981 Apr;4(4):471-5. doi: 10.1016/s0190-9622(81)80261-7. PMID: 7229150.


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