Four cases of PML were reported in plaque psoriasis patients, an incidence of approximately one in 500 treated patients. As PML is very rare, it is extremely unlikely that the four reported cases were due to chance and given that PML occurs primarily in patients who are immunosuppressed, the association is likely causal. Phase 2 and 3 randomized controlled trials (RCT’s) typically involve 500-3,000 patients, and although they are the gold standard for assessing efficacy of a drug, they have numerous limitations with respect to assessing safety 14. Although the majority of PML cases occur in severely immune-suppressed individuals, with HIV-1 infection as the predominant factor, PML has been increasingly diagnosed in patients treated with biological therapies such as monoclonal antibodies that modulate immune system functions. Monoclonal antibodies that target the cell adhesion molecules VLA-4 (natalizumab; Tysabri for multiple sclerosis and Crohn’s disease) or LFA-1 (efalizumab; Raptiva for severe forms of plaque psoriasis) to prevent extravasation of inflammatory T cells into tissues, or target the cell surface marker CD20 (rituximab; Rituxan for hematologic malignancies and rheumatoid arthritis) to deplete peripheral circulating B cells, have all been associated with PML.
Efalizumab (trade name Raptiva, Genentech, Merck Serono) is a medication designed to treat psoriasis. Four cases of PML were reported in plaque psoriasis patients, an incidence of approximately one in 500 treated patients. Psoriasis patients previously treated with PUVA and to a lesser extent, methotrexate or other immunosuppressive agents, UVB, coal tar, or radiation therapy, are at an increased risk of developing skin malignancies when taking Cyclosporine Oral Solution USP MODIFIED. Cases of PML have been reported in patients treated with Cyclosporine Oral Solution USP MODIFIED. Five cases of lymphoma were detected: four in a survey of approximately 2,300 patients treated with Cyclosporine for rheumatoid arthritis, and another case of lymphoma was reported in a clinical trial. It was first isolated from the brain of a patient with Hodgkin disease in 1971, and since then the etiological agent of the progressive multifocal leukoencephalopathy (PML) was considered. Among 82,732 patients treated with natalizumab worldwide until to 2011, 102 cases of PML have been reported, and this number seems expected to rise.
A subsequent analysis suggested that the risk was approximately 1 PML case per 1000 treated patients per 18 months of therapy. In 2008 and early 2009, Genentech reported that 3 patients receiving efalizumab monotherapy for treatment of plaque psoriasis had developed fatal cases of PML. Of this group, about 23 500 had received less than 2 years of treatment; 1850 had received 2 to 3 years; 700, 3 to 4 years; The 2 reported fatal PML cases in rituximab-treated patients with SLE were initially reported by Genentech in December 200626and occurred among approximately 10 000 patients estimated by the company to have received rituximab for treatment of SLE. 12 reported 3 patients with recalcitrant cutaneous sarcoidosis who were treated with FAEs. Recently, four cases with virus-related progressive multifocal encephalopathy (PML) were reported in patients with psoriasis under FAEs treatment 15. Our patient had initially a low lymphocyte count, which increased to 500/cm3 under treatment with Fumaderm Initial. Recently, cases of PML were also observed in patients under treatment with biologics, including monoclonal antibodies (mAbs). Ortho Biotech), in CD, severe forms of plaque psoriasis, rheumatoid arthritis (RA) and spondyloarthritis9, 10, 11. JCPyV load values of MS cohort and CD cohort are reported in table 1 and table 4, respectively.
Figure 1 Development of monoclonal antibodies: structure and function. This is reflected in mAbs having approval rates of around 20 compared with 5 for new chemical entities. By mid-2009 there were a total of 14 cases of PML in patients with multiple sclerosis treated with natalizumab. CD11a-specific mAb efalizumab (Raptiva; Genentech) has been associated with four confirmed cases of PML when used to treat patients with chronic plaque psoriasis. Therapies that slow progression of disease are available; therefore, early diagnosis and treatment are important in limiting the impact of this potentially devastating disease. On average, patients have clinical relapses every 1 to 2 years during the relapsing-remitting phase of the disease. By blocking VLA-4, fewer inflammatory cells enter the brain and thereby blunt CNS inflammation typical of MS. Since early diagnosis and treatment of HIV can help prevent serious sequelae in the source patient and further dissemination of HIV to sexual contacts, it is considered here as an emergency. Other skin findings that have been reported in association with primary HIV infection include a papulopustular and vesicular exanthem, urticaria, and desquamation of the palms and soles7,11,15. Interestingly, though psoriasis is thought to occur in HIV+ patients at approximately the same frequency as in the immuncompetent population (between 1-3 ), its clinical features vary. Medium power view of a skin biopsy from a patient with pemphigus vulgaris showing acantholysis of the suprabasal keratinocytes leaving a single layer of basal keratinocytes attached to the basement membrane (tombstone pattern), which forms the floor of an intraepidermal blister. The estimated incidence of pemphigus is 1-16 cases per year per million people 1,2. The positivity rate is approximately 79-90 38. A small study comprised of 4 patients with mild PF and 3 with mild PV were treated with the very potent topical corticosteroid, Clobetasol propionate 0.