British Association of Dermatologists' Guidelines for the Management of Pemphigus Vulgaris 2017

K.E. Harman; D. Brown; L.S. Exton; R.W. Groves; P.J. Hampton; M.F. Mohd Mustapa; J.F. Setterfield; P.D. Yesudian


The British Journal of Dermatology. 2017;177(5):1170-1201. 

In This Article

Disease Monitoring

Decisions concerning ongoing disease management will be based on making an assessment of disease activity. The simplest way of monitoring disease activity is clinically, which can be done more objectively by using clinical disease scoring systems. Clinical disease activity assessment can be supplemented with immunological measures and quality-of-life scores.

Disease Severity Scoring

Numerous disease severity scoring systems exist, making it difficult to compare data between studies. Two validated severity scoring systems that have become frontrunners are the Pemphigus Disease Area Index (PDAI) and the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS),[31–34] each taking 2–5 min to complete.[32,34] These have also been validated for use in oral PV but are inferior to another system, the Oral Disease Severity Score, which may be combined with ABSIS or PDAI in patients with skin or extraoral mucosal sites.[35]

It is recommended that disease severity is scored in routine clinical practice. It is essential in clinical trials.

Immunological Monitoring

IIF can be used to express the quantity of pemphigus antibodies in serum as a series of discontinuous serum dilutions. It is subjective and operator dependent and the titre depends on the substrate used, due to variable amounts of antigen being expressed at different sites. In general, mucosal substrates are better for detection of desmoglein 3 antibodies, and skin better for detection of desmoglein 1 antibodies, with the use of both substrates enhancing sensitivity.[36] IIF titres can reflect disease activity, but the relationship is not perfect and examples of active disease with negative IIF or vice versa exist such that IIF cannot be relied upon for disease monitoring. Whether IIF using two substrates is more useful for disease monitoring is yet to be demonstrated.

Desmoglein 1 and 3 ELISAs are sensitive and specific assays providing an objective and quantitative measure of antibody levels. In general, ELISA levels are related to disease activity, with desmoglein 1 antibody levels associated with skin severity and desmoglein 3 levels associated with oral severity.[37–41] Titres usually fall with treatment and disease remission.[40,42–45] Patients followed over time also show fluctuations in ELISA levels that mirror disease activity[37,41] but, as with IIF, the relationship is not perfect: examples of patients with inactive disease and high ELISA titres and vice versa are reported,[37,42–44] and one study found that changes in desmoglein 3 antibody levels did not correlate with clinical activity.[43] Some of these problems reflect saturation of the ELISAs at higher values, which could be overcome by increasing the serum dilution.[46]

The use of sequential salivary antidesmoglein 3 IgG titres as a biomarker of disease activity is an emerging area of interest, and titres have recently been shown to reflect oral disease activity.[26]

In general, falling or persistently low and negative IIF or ELISA titres are a good sign, such that immunosuppression could be tapered. Rising or persistently high titres should be a cause for concern. Where facilities exist to follow titres, the information could be used as an adjunct to clinical assessment, but due to the imperfections of the assays discussed, good clinical judgement remains paramount.