Table 3.
Conventional treatment strategies.
| Skin Disease | Drugs | Mode of action | References |
|---|---|---|---|
| Atopic Dermatitis | Calcineurin inhibitors: tacrolimus and pimecrolimus | Prevent the activation of NFAT by inhibition of calcineurin phosphatase resulting in prevention of activation of T cells, mast cells, and cytokines like IL-4, -5, - 31, TNF-α. | Mayba and Gooderham, 2017; Papier and Strowd, 2018 |
| Phosphodiesterase inhibitors: crisaborole and Apremilast. | Prevent the conversion of cAMP to AMP that leads to accumulation of cAMP. This in turn causes suppression of NFAT, and NFKB pathways involved in inflammation. | ||
| Janus Associated Kinase-Signal Transducer and Activator of Transcription (JAK - STAT) inhibitors: Tofacitinib | Inhibit phosphorylation of JAK-1 and JAK-3 and prevent the activation of STATs.Reduce immune cell polarization and cytokine production. | ||
| Cytokine and cytokine signaling inhibitors: Dipulimab, Lebrikizumab, and Nemolizumab. | Dipulimab is an antibody that binds to the alpha subunit of the IL-4 receptor. This inhibits the pathways driven by IL-4 and IL-13 and reduces the expression level of genes involved in epidermal hyperplasia and immune cell activation. Lebrikizumab is an antibody that blocks IL-13 and the signaling pathways associated with it. Nemolizumab is an antibody against receptor A of IL-31. It blocks homing of CLA+ T cells and decrease pruritus. |
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| Systemic immunosuppressants: Ciclosporin A, Methotrexate, and Benvitimod | Inhibition of immune cell recruitment and production of pro-inflammatory cytokines. | ||
| Antihistamines: Hydroxyzine, Diphenhydramine, Chlorpheniramine | Inhibition of allergic responses and associated pruritis. | ||
| Psoriasis | Vitamin D3 analogues: Calcitriol, Tacalcitol, and Calcipotriol. | Antiproliferative, pro-differentiation, suppression of T cell activation, increased production of Tregs, MHC-II suppression. | Duvic et al., 1997; Trémezaygues and Reichrath, 2011; Uva et al., 2012; Almutawa et al., 2013; Jacobi et al., 2015; Torsekar and Gautam, 2017 |
| Calcineurin inhibitors Pimecrolimus, and Tacrolimus. | Same as above. | ||
| Keratolytics - Salicyclic acid, and urea. | Increases shedding of corneocytes and reduction of pH. | ||
| Topical corticosteroids | Vasoconstrictive, antiproliferative, anti-inflammatory, and immunosuppressive. | ||
| Retinoids Tazarotene, and Acitercin | Binds to family of retinoic acid receptors - down-regulates keratinocyte differentiation, proliferation, and inflammation. | ||
| UV based therapy | Inhibition of inflammatory pathways, induction of apoptosis, downregulation of TH1/TH17 inflammatory axis, cell cycle arrest. | ||
| Phosphodiesterase inhibitor: Apremilast | Same as above | ||
| Systemic immunosuppressants: Ciclosporin, and Methotrexate. | Same as above | ||
| Cytokine and cytokine signaling inhibitors: Adalimumab, Etanercept, Infliximab, Secukinumab, and Ustekinumab. | Adalimumab, Etanercept, and infliximab are antibodies against TNF that result in inhibition of inflammation and immune cell recruitment. Secukinumab binds and neutralizes IL-17 that cause reduction in inflammation, immune cell recruitment and epidermal hyperproliferation. Ustekinumab binds to common receptor for cytokines IL-12 and IL-23 thereby reducing the activation and differentiation of Natural killer (NK) cells and CD4+ T cells. |
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| Anti-hyperproliferative Dithranol | Impedes DNA replication and reduces elevated cGMP levels. | ||
| EB | Treatment involves draining blisters using sterile needles, surgeries for separating fused digits. | Nystrom et al., 2015 | |
| A small-molecule angiotensin II type 1 receptor antagonist Losartan | Reduction in TGFβ expression slowing down fibrosis in RDEB. | ||
| NSAIDs, analgesics | Suppress inflammation. | Goldschneider et al., 2014 | |
| Squamous cell carcinoma | Single or in combinations—Surgery, thermal ablation, radiation | Ribero et al., 2017; Yanagi et al., 2018 | |
| Epidermal growth factor receptor (EGFR) inhibitor: Cetuximab, Panitumumab, gefitinib, and erlotinib | Cetuximab and Panitumumab monoclonal antibody binds EGFR and inhibits EGF mediated signaling. Gefitinib and Erlotinib bind to tyrosine kinase domain of EGFR. | ||
| Tyrosine kinase inhibitors: imatinib | Imatinib binds close to ATP binding site of tyrosine kinases thereby preventing its activity. | ||
| 26S proteasome inhibitor: Bortezomib | Bortezomib contains a boron atom which binds to active site of 26S proteasome and prevents degradation of ubiquitin tagged proteins thereby enhancing cell death. | ||
| Apoptosis inducer: Isotrenoin | Induces apoptosis in sebaceous gland cells and enhances neutrophil gelatinase-associated lipocalin (NGAL) production which induces sebocyte apoptosis. | ||
| Cytotoxic drugs: 5-Fluorouracil (5-FU), Doxorubicin, and Cisplatin | 5-FU is an inhibitor of thymidylate synthase, which inhibits DNA replication. Doxorubicin inhibits topoisomerase II action. Cisplatin cross links DNA and prevents mitosis. | ||
| Immune checkpoint inhibitors: Anti-PD-1: Nivolumab and Pembrolizumab Anti-CTLA-4: Ipilimumab |
Cytotoxic T cell mediated killing of tumor cells. |
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| Basal cell carcinoma | Surgical excision, cryotherapy, Laser therapy, Mohs micrographic surgery, photodynamic therapy and radiotherapy. | Lewin and Carucci, 2015; Migden et al., 2018 | |
| Inhibitors of DNA replication: 5-FU. | Same as above. | ||
| Hedgehog pathway inhibitors: vismodegib and sonidegib | It is an antagonist of smoothened which in turn causes inactivation of GLI-1 and GLI-2 transcription factors. | ||
| Immune response modifier: imiquimod | Activates innate immune cells and incites an inflammatory response. This, in turn, activates adaptive immune cells. | ||
| Melanoma | BRAF inhibitor: vemurafenib and dabrafenib | Inhibit the mutated kinase domain of BRAF involved in MAPK signaling. | Johnson and Sosman, 2015 |
| MEK inhibitor: Trametinib | Allosteric inhibitor of MEK1/2 that is constitutively activated. | ||
| Immunotherapy: Interleukin-2 |
Activates immune system to attack cancer cells. Also stimulate melanoma cells to secrete chemoattractants for immune cells. |
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| Anti-PD-1: Nivolumab and Pembrolizumab | Same as above. | ||
| Anti-CTLA-4: Ipilimumab | Same as above | ||
| Merkel cell carcinoma | Mohs micrographic surgery, lymph node dissection and radiation therapy. Sentinel lymph node biopsy | Tello et al., 2018 | |
| Chemotherapy: Somatostatin analogs | Inhibition of endocrine tumor growth. | ||
| mTOR inhibitors | Blocking PI3K/Akt/mTOR pathway and inhibit cell proliferation and tumor growth. | ||
| Immune checkpoint inhibitors: | |||
| Anti-PD-1: Nivolumab and Pembrolizumab avelumab | Same as above. | ||
| Anti-CTLA-4: Ipilimumab |
Same as above. | ||
| Cutaneous lymphoma | Topical Corticosteroids | Wollina, 2012 | |
| Phototherapy | Use of UVA on skin, which results in self destruction of T cells. | ||
| Topical chemotherapy: Mechlorethamine and carmustine. |
Chemically modify DNA and prevent tumor growth. | ||
| Topical imiquimod | Aid in the release of IFN-γ and cytokines for suppressing tumor growth. | ||
| Cytokine therapy: TNF-α | Stimulate immune system to target tumor cells. |