By Gary M. White, MD
Paraneoplastic pemphigus (PNP) is an autoimmune, mucocutaneous erosive and blistering disease which usually develops in a patient with a malignancy.
Extensive erosions of the oral cavity, conjunctiva, vagina, penis and lips are characteristic. The mucosal lesions may resemble lichen planus, e.g. with erosions, or lichenoid lesions. They frequently extend beyond the vermilion border of the lips. Cutaneous lesions may resemble pemphigus vulgaris, erythema multiforme, lichen planus, bullous pemphigoid, or ocular cicatricial pemphigoid. Target lesions may occur on the palms, and tense bulla on the skin.
Myasthenia gravis (MG) is a complication of paraneoplastic pemphigus. Acetylcholine receptor, acetylcholinesterase antibodies are prominent in patients with PNP, especially those with dyspnoea [BJD 2015;172;968]. In the referenced article, 39% of patients with PNP experienced muscle weakness, and 35% were diagnosed with MG.
PNP is rare in children but does occur [BJD 1997;136;115].
About 80% of patients have anti-desmoglein3 (Dsg3) antibodies, and about one-third have anti-desmoglein1 (Dsg1) antibodies in ELISA. However, 10-20% of patients with PNP are negative for both anti-Dsg1 and anti-Dsg3 antibodies. In a recent study, In a recent study, nineteen (18·6%), 42 (41·2%) and 62 (60·8%) patients revealed positive reactivity with Dsc1, Dsc2 and Dsc3, (desmocollin) and 32 (60%) of 53 patients had antibodies to A2ML1 [BJD 2015;173;1447]. Thus, antibodies to both Dscs and A2ML1 are useful in the diagnosis of PNP.
DIF shows IgG and/or C3 along the BMZ and in the intercellular space. Positive IIF using rat bladder transitional epithelium was thought to be highly specific, helping to differentiate these patients from those with pemphigus and neoplasia. However, this has been found not to be true, as 20-25% of patients show negative IIF using bladder epithelium [BJD 2015;173;1447]. No single substrate is both highly sensitive and specific. Cases of suspected PNP where no serum antibodies could be found have been described.
Workup and treatment should involve multiple specialties. It is often disappointing. Approximately 90% of patients will die within 2 years of diagnosis. Leading causes of mortality include bronchiolitis obliterans, infection and death from the malignancy. Cases in which the neoplasm is benign and can be completely excised may allow for long term survival [Dermatology 1999;199;63]. Obviously, any neoplasm should be treated appropriately.
High dose prednisone is usually tried first. Steroid sparing agents added include azathioprine, mycophenolate mofetil, cyclosporine and cyclophosphomide.
Rituximab has been used with success in some cases but has failed in others. IVIG and plasmapheresis have been used. A small percent of cases have limited/mild disease.
Dermatology Online Journal 14:6, 2008
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