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Investigational Drugs bring hope to those suffering from Psoriasis

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Psorisis lesions

Psoriasis is a chronic inflammatory condition of the skin characterized by sharply demarcated red skin lesions covered with silvery scales. The lesions of psoriasis are commonly seen in the elbow, knee, scalp, and lower back of the body though they may involve any part of the body. Psoriasis is non-contagious meaning it cannot be transmitted to you from an infected person.

Psoriasis is one of the most common dermatological disorders in the world affecting up to 1% of the world population. The condition is common equally in males and females.

Causes of Psoriasis

The cause of psoriasis is still poorly understood but it has shown to occur in genetically predisposed individuals. More than 50% of patients with psoriasis show positive familial history for it. It is thought that in these genetically predisposed individuals dysregulated immune response to certain environmental triggers leads to increased production of epidermal cells which gives rise to the characteristic skin lesion. Possible triggers may be skin injury, infections, stress, and certain medications including Lithium and anti-malarial drugs.

Morphology of the Lesion

The lesion of psoriasis is sharply demarcated, red, indurated, and is mounted with scales. Hypo-pigmented halo may be present surrounding the lesion. The size and number of lesions can be variable and individual lesions can merge to form larger lesions.

Symptoms of Psoriasis

Common clinical features of psoriasis include:
  • Presence of characteristic rash covered with scales which may or may not be itchy
  • Discoloration and pitting of fingernails and toenails, which may result in it to detach from the nailbed
  • Some patients may develop painful joints
 

Diagnosing Psoriasis

Your doctor can make the diagnosis of the disease by looking at the lesion, its morphology, and distribution or through two simple bed-side tests called the Auspitz test and the Grattage test.

The doctor may take a short medical history to check for positive family history and if it is more common during the winter seasons. Biopsy of the lesion may be required in rare cases to diagnose the type of psoriasis and to differentiate it from conditions forming similar lesions.

Management of Psoriasis

There is no definitive treatment for psoriasis, current modes of therapy aim at decreasing disease activity, and improving symptoms. The treatment is individualized and depends upon multiple patient and disease factors.

Topical Agents

  • Steroids: Topical steroids can be used effectively for symptom relief in mild to moderate localized cases of psoriasis. Its long term use is not recommended as it may lead to skin atrophy.
  • Vitamin D analog: Calcitriol and calcipotrial creams reduce psoriatic symptoms in mild to moderate cases when used along with topical steroids or as an alternative to it.
  • Coal tar: Coal tar is an old method of treatment of psoriasis. It is a safe drug for topical application and helps reduce scales and inflammation. It can be used as an adjunct to systemic therapy or phototherapy.
  • Dithranol: Low concentration Dithranol is effective as a short term treatment of psoriasis, it helps reduce cell proliferation. However higher concentrations may lead to staining or even burns. It can also be combined with phototherapy.
 

Phototherapy

It involves the use of natural and artificial lights to treat widespread psoriasis not responding to topical drugs. Before the therapy, you will be given tablets containing compounds that make your body more sensitive to light. Combining phototherapy with other treatments increases the efficacy of the treatment. 

Systemic Agents

Various systemic agents can be used for severe, widespread psoriasis.
  • Methotrexate: It is an effective agent in suppressing cell proliferation and inflammation. It is also useful in the treatment of psoriatic arthritis. Long term use of methotrexate can lead to liver damage. It should be avoided in pregnancy as it is a known teratogenic agent.
  • Acitretin: It is useful in the treatment of various forms of psoriasis and is useful in treating severe cases of psoriasis where immunosuppression is not desired. It is also a known teratogenic drug.
  • Cyclosporine: It is an effective immune-suppressant in treating all forms of psoriasis. However, it should be used with caution as it can cause a wide range of side effects.
  • Biological response modifiers: These drugs effectively suppress chronic inflammation in psoriasis by destroying overactive immune cells. These drugs are indicated in severe cases of psoriasis not responding to other treatments or in cases where other drugs are contraindicated. These drugs are given as injections. Drugs of this class include:
    • Etanercept
    • Alefacept
    • Infliximab
    • Efalizumab

In addition to these treatments, doctors may recommend patient counseling. They should be assured that the disease is non-contagious and several treatment options are available. Keeping patients at mental peace may enhance the effects of certain therapies. Doctors will inform patients that there will be periods of remission in between the disease and treatment is usually long-term and suppressive rather than curative.

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Treatment Modalities Currently Undergoing Clinical Trials

  • IDP-118: A clinical trial to assess the efficacy, safety of halobetasol propionate and tazarotene lotion (IDP-118) in the treatment of moderate to severe cases of psoriasis in children is currently underway. It is in Phase-4 of the clinical trial.
  • Biological Therapy: An observational study to assess the long-term efficacy and safety of biological response modifiers like Etanercept, Infliximab, adalimumab, and Efalizumab in the treatment of moderate to severe cases of Psoriasis is being conducted.
  • Guselkumab: Guselkumab is one of the most potent medications in the treatment of moderate to severe cases of psoriasis but is very costly. A clinical trial of Guselkumab is currently underway which aims at finding its therapeutic index in patients with psoriasis. It is currently in Phase -4 of the clinical trial.  
  • Tildrakizumab: The drug Tildrakizumab (biologic response modifier) is currently under clinical trial to assess its efficacy, safety, and its effect on the improvement of disease-related quality of life in patients suffering from psoriasis. It is currently under Phase-4 of its clinical trial.
  • Risankizumab: Risankizumab is a drug that has been approved for the treatment of psoriasis. It is currently being studied for its safety and efficacy in the treatment of plaque psoriasis.
  • Ensitlar: The use of Enstilar (Calcipotriene and Betamethasone Dipropionate Foam) in combination with a biologic ixekizumab (Taltz) is being studied for its effectiveness in the treatment of psoriasis. It is currently in Phase-4 of its clinical trial. 
   
References:
  1. Paola Di Meglio,Federica Villanova, Frank O. Nestle. Psoriasis. Cold Spring Harb Perspect Med. 2014 Aug; 4(8): a015354.
  2. Adriana Rendon and Knut Schäkel. Psoriasis Pathogenesis and Treatment. Int J Mol Sci. 2019 Mar; 20(6): 1475.


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