Neil J. Korman

Guidelines of care for the management of psoriasis and psoriatic arthritis Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this first of 5 sections of the guidelines of care for psoriasis, we discuss the classification of psoriasis; associated comorbidities including autoimmune diseases, cardiovascular risk, psychiatric/psychologic issues, and cancer risk; along with assessment tools for skin disease and quality-of-life issues. Finally, we will discuss the safety and efficacy of the biologic treatments used to treat patients with psoriasis.

Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia.

Paraneoplastic pemphigus is a newly recognized disease that occurs in some patients with lymphoproliferative neoplasms and occasionally, solid tumors. Patients present with an acute illness of the mucosa and skin that shares clinical and histologic features with erythema multiforme, toxic epidermal necrolysis, and pemphigus vulgaris. These patients have antibodies against a complex of epithelial proteins that are present in desmosomes and hemidesmosomes. The course is usually fatal, except in some patients who undergo total resection of their neoplasm.

Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: Overview and guidelines of care for treatment with an emphasis on the biologics

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this second of 5 sections of the guidelines of care for psoriasis, we give an overview of psoriatic arthritis including its cardinal clinical features, pathogenesis, prognosis, classification, assessment tools used to evaluate psoriatic arthritis, and the approach to treatment. Although patients with mild to moderate psoriatic arthritis may be treated with nonsteroidal anti-inflammatory drugs and/or intra-articular steroid injections, the use of disease-modifying antirheumatic drugs, particularly methotrexate, along with the biologic agents, are considered the standard of care in patients with more significant psoriatic arthritis. We will discuss the use of disease-modifying antirheumatic drugs and the biologic therapies in the treatment of patients with moderate to severe psoriatic arthritis.

National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening

There have been several articles and reports in recent months about comorbidities and risks that affect psoriasis patients in addition to their underlying disease. This piece reviews the current literature and begins to address what should be done with this new information by updating the clinician about what health screening tests, preventative exams, and referrals should be considered in this population.

Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus

Our scientific knowledge of pemphigus has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in pemphigus. A major obstacle in comparing therapeutic outcomes between centers is the lack of generally accepted definitions and measurements for the clinical evaluation of patients with pemphigus. Common terms and end points of pemphigus are needed so that experts in the field can accurately measure and assess disease extent, activity, severity, and therapeutic response, and thus facilitate and advance clinical trials. This consensus statement from the International Pemphigus Committee represents 2 years of collaborative efforts to attain mutually acceptable common definitions for pemphigus. These should assist in development of consistent reporting of outcomes in future studies.

Topical capsaicin treatment of chronic postherpetic neuralgia

Uncontrolled studies have indicated that topically applied capsaicin may be a safe and effective treatment for postherpetic neuralgia. In a double-blind study 32 elderly patients with chronic postherpetic neuralgia were treated with either capsaicin cream or its vehicle for a 6-week period. Response to treatment was evaluated by visual analogue scales of pain and of pain relief, together with changes in a categoric pain scale and in a physicians global evaluation. Significantly greater relief in the capsaicin-treated group compared with vehicle was observed for all efficacy variables. After 6 weeks almost 80% of capsaicin-treated patients experienced some relief from their pain. Because capsaicin avoids problems with drug interactions and systemic toxicity, we suggest that topical capsaicin be considered for initial management of postherpetic neuralgia.

Demonstration of an Adhering-Junction Molecule (Plakoglobin) in the Autoantigens of Pemphigus Foliaceus and Pemphigus Vulgaris

Pemphigus foliaceus and pemphigus vulgaris are skin diseases in which antibodies against the cell surface of keratinocytes destroy the adhesion between epidermal cells, producing blisters. Patients with pemphigus foliaceus have antibodies to a complex of three polypeptides of 260, 160, and 85 kd (the foliaceus complex), whereas patients with pemphigus vulgaris have antibodies to a complex of 210-kd, 130-kd, and 85-kd polypeptides (the vulgaris complex). The 160-kd polypeptide of the foliaceus complex has been identified as desmoglein, a desmosomal glycoprotein. We suspected that the 85-kd component in both these antigenic complexes might be plakoglobin, another molecule in the adhering junctions of cells. To characterize these antigenic complexes, we used the serum of five patients with pemphigus foliaceus, that of four patients with pemphigus vulgaris, and monoclonal antiplakoglobin antibodies. We found that monoclonal antibodies to plakoglobin immunoprecipitated the 85-kd polypeptide from the dissociated foliaceus and vulgaris complexes and precipitated both complexes from epidermal extracts. Serum from patients with pemphigus foliaceus or pemphigus vulgaris (but not from four normal controls) bound desmoglein and the 130-kd polypeptide, respectively, showing that these peptides (and not plakoglobin) are the antigenic binding sites in these disorders. We conclude that plakoglobin, a protein of the adhering junctions of epidermal cells, is the 85-kd molecule in the antigenic complexes found in both pemphigus foliaceus and pemphigus vulgaris, although it is not the binding site in either disorder.

National Psoriasis Foundation consensus statement on screening for latent tuberculosis infection in patients with psoriasis treated with systemic and biologic agents

BACKGROUND Chronic immunosuppression is a known risk factor for allowing latent tuberculosis (TB) infection to transform into active TB. Immunosuppressive/immunomodulatory therapies, while highly efficacious in the treatment of psoriasis and psoriatic arthritis, may be associated with an increased rate of active TB in patients receiving some of these therapies. OBJECTIVE Our aim was to arrive at a consensus on screening for latent TB infection in psoriasis patient treated with systemic and biologic agents. METHODS Reports in the literature were reviewed regarding immunosuppressive therapies and risk of TB. RESULTS Screening patients for latent TB infection before commencement of treatment is of utmost importance when beginning treatment with the tumor necrosis factor-alpha inhibitors, T-cell blockers, cyclosporine, or methotrexate. The currently recommended method for screening is the tuberculin skin test. It is preferable that positively screened patients be treated with a full course of latent TB infection prophylaxis before immunosuppressive/immunomodulatory therapy is initiated. However, in the opinion of many experts, patients may be started on the immunosuppressive/immunomodulatory therapy after 1 to 2 months, if their clinical condition requires, as long as they are strictly adhering to and tolerating their prophylactic regimen. LIMITATIONS There are few evidence-based studies on screening for latent TB infection in psoriasis patients treated with systemic and biologic agents. CONCLUSIONS The biologic TNF-alpha inhibitors are very promising in the treatment of psoriasis. However, because TNF-alpha is also an important cytokine in preventing TB infection and in keeping latent TB infection from becoming active disease, the use of TNF-alpha inhibitors has been associated with an increased risk of developing active TB. A higher incidence of TB has also been reported with other immunosuppressive/immunomodulatory treatments for psoriasis. It is, therefore, of utmost importance to appropriately screen all patients for latent TB infection prior to initiating any immunologic therapy. Delaying immunologic therapy until latent TB infection prophylaxis is completed is preferable. However, if the patient is adhering to his prophylactic regimen and is appropriately tolerating the regimen, therapy may be started after 1 to 2 months if the clinical condition requires.

Consensus Guidelines for the Management of Plaque Psoriasis

The Canadian Guidelines for the Management of Plaque Psoriasis were reviewed by the entire National Psoriasis Foundation Medical Board and updated to include newly approved agents such as ustekinumab and to reflect practice patterns in the United States, where the excimer laser is approved for psoriasis treatment. Management of psoriasis in special populations is discussed. In the updated guidelines, we include sections on children, pregnant patients or pregnant partners of patients, nursing mothers, the elderly, patients with hepatitis B or C virus infections, human immunodeficiency virus-infected patients, and patients with malignant neoplasms, as well as sections on tumor necrosis factor blockers, elective surgery, and vaccinations.

Paraneoplastic pemphigus: A report of three cases including one long-term survivor

BACKGROUND Paraneoplastic pemphigus is a newly described autoimmune disease characterized by painful mucosal ulcerations and polymorphous skin lesions in association with an underlying neoplasm. All reported patients with an associated malignant neoplasm have had a poor prognosis. OBJECTIVE We present three new cases of paraneoplastic pemphigus associated with a malignant neoplasm and further characterize this disease. METHODS We used clinical criteria, histologic and immunopathologic examinations, and immunophenotyping to characterize this disease. In addition, we performed immunoprecipitation studies with extracts of radiolabeled human keratinocytes to characterize the antigens to which patient serum binds. RESULTS All three patients had clinical, histologic, and immunopathologic findings that were strongly suggestive of paraneoplastic pemphigus. Their sera immunoprecipitated a complex of four polypeptides from human keratinocyte extracts with molecular weights of 250, 230, 210, and 190 kd, confirming the diagnosis of paraneoplastic pemphigus. The 250, 230, and 210 kd antigens comigrated with desmoplakin I, the 230 kd bullous pemphigoid antigen, and desmoplakin II, respectively. Lymphocyte immunophenotyping revealed large populations of monoclonal CD19+, CD5+ B cells in two cases. Although two of the patients died, one patient is alive and well 2 years after the diagnosis of paraneoplastic pemphigus. CONCLUSION We report three cases of paraneoplastic pemphigus. One patient is alive and well 2 years after diagnosis, which suggests that a subgroup of patients may have a more benign course.