Scleroderma



Scleroderma


Sameh S. Zaghloul, Najat A.Y. Marraiki and Mark J.D. Goodfield


Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports


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Systemic sclerosis (SSc), often called scleroderma, is a rare multisystem disease characterized by skin fibrosis, autoantibody production, and vascular abnormalities often leading to visceral disease. It can affect any organ system, particularly the gastrointestinal tract, kidney, heart, and lungs. Patients typically present with cutaneous sclerosis or Raynaud phenomenon (RP). The degree of skin involvement defines the clinical subset of the disease. Diffuse cutaneous SSc (dcSSc) involves the skin proximal to the neck, elbows, or knees, whereas involvement distal to these sites is known as limited cutaneous SSc (lcSSc); some authors include an intermediate group. Localized scleroderma, or morphea, is a different condition.



Management strategy


Limited cutaneous and dcSSc, with different severities and survivals, have been recognized as distinct subsets. Some authors have suggested an intermediate cutaneous form with intermediate survival.


In most cases cutaneous lesions and RP precede systemic involvement. The face and hands are typically involved, with patients displaying a characteristic shiny appearance of the skin and complaining of increased skin stiffness or rigidity. To date, no treatment has proved uniformly effective in modifying the course of the disease and there is no specific therapy for the skin, although dry skin should be cared for daily using emollient creams. Topical 0.025–0.05% tretinoin may improve the perioral radial furrows and facial tightening.


UVA phototherapy (PUVA and UVA1) has been reported to be effective in reducing skin thickness. Vasodilators such as nifedipine reduce vasospasm and improve peripheral blood flow. Also, losartan, an antagonist of angiotensin II receptor type I, has been found to be effective in reducing the severity and frequency of attacks of RP. Parenteral prostacyclin analogs such as iloprost also improve both the severity and frequency of RP. Both low-dose prednisolone 20 mg/day and methotrexate 15–25 mg/week have been shown to reduce skin thickness scores. Cyclosporine 3–4 mg/kg/day may improve skin induration but has no effect on internal organ involvement. It should be used with caution as renal involvement with SSc is not uncommon. Mycophenolate (0.5–1.5 g bid) is of value for both skin and lung involvement. Cyclophosphamide 1–2 mg/kg/day is of proven value in reducing skin scores and preventing the development of lung fibrosis and other complications, and pulsed therapy with cyclophosphamide is also effective and possibly safer.


Biologics, including rituximab, infliximab, basiliximab and imatinib, have all been investigated with varying success. Trials of stem cell transplantation show promising efficacy, but have significant side effects. Respiratory complications of SSc develop in roughly 30% of patients. Pulmonary hypertension (PAH) may occur and should be confirmed by appropriate investigation. Iloprost infusions have also been shown to reduce PAH. Angiotensin-converting enzyme (ACE) inhibitors are particularly effective in reducing the renal complications of the disease, and early treatment may prevent the onset of renal failure. Proton pump inhibitors treat esophageal disease effectively. Recent randomized controlled trials have suggested that oral minocycline and D-penicillamine are not effective in SSc. Although SSc carries a high case-specific mortality, there have been significant advances in the management of skin, renal, and pulmonary complications. The identification of novel signaling pathways and mediators that are altered in SSc and contribute to tissue damage allows their selective targeting. This in turn opens the door for novel therapeutic strategies using novel compounds, or innovative ways of using already approved drugs.



Specific investigations












First-line therapies















image Nifedipine A
image Iloprost A
image ACE inhibitors B









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Aug 7, 2016 | Posted by in Dermatology | Comments Off on Scleroderma

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