By Professor Martin M Black, MD
Pemphigus and its variants are rare autoimmune disorders characterized by loss of cell to cell cohesion between keratinocytes leading to intra-epidermal blistering. In all types of pemphigus, antibodies are directed against antigens in the intercellular substance between keratinocytes and in a substantial number of active cases, these pemphigus antibodies can be detected in the general blood circulation.
Pempigus vulgaris (PV) is characterized by flaccid blistering and erosions of the skin and mucous membranes. Involvement within the mouth may often precede the skin erosions and may persist even long after skin lesions subside. It is therefore important to remember that involvement of the oral cavity may take the patient to see dental surgeon, rather than a dermatologist in the first instance. However, in pemphigus foliaceus (PF) the blistering tends to be more superficial than in the vulgaris form of pemphigus and the mucous membrane areas are not involved.
For many years, London, one of the largest cities in the world, has been truly international, with large populations of different ethnic groups living together within a 50 mile radius. This multi ethnicity provides an ideal opportunity to study the epidemiology of pemphigus and provide information on ethnic groups and numbers of involvement. We have recently surveyed our 140 patients of pemphigus who attend our St. John’s Institute for Diseases of the Skin. In our group, the male to female ratio was 1:1.12 (77 F, 63 M) and the mean age of disease onset was 44 years. This of course, is in the prime of adult life and has important economic consequences for patient sufferers, particularly if the disease is severe and the treatment likely to be longstanding. In our patients, the ethnic break-up of our group was British 51 (36.4%), Asian (Indian subcontinent) 46 (32.8%). This is quite a high figure and corroborates other evidence that pemphigus is much more common in patients living in the Indian subcontinent countries. Of Afro-caribbean countries, 15 (10.7%) had pemphigus, Middle-East 12 (8.5%) and curiously, Jewish 9 (6.4%) is rather low, as all the text books state that pemphigus is much more common in those of Jewish ancestry. Others of mixed ethnicity are fewer in number and comprise 2 Greeks and 2 Chinese. This evidence certainly would indicate the genetic factors and have an important role in predisposing individuals to developing pemphigus. It is therefore an opportunity for us to develop this theme further and we will be doing this over the next few years, looking at the genetic haplo types.
For over 25 years, our immunodermatopathological laboratory at our Institute has specialized in diagnosis of auto-immune bullous diseases. We have developed considerable experience with immunofluoresence techniques to detect the presence of antibodies in the skin by the direct method and in the serum by indirect methods. It is now well known that the PF antigen is a transmembrane glycoprotein called desmoglein 1 (Dsg1) and the PV angiten is termed desmoglein 3 (Dsg3). These desmogleins are adhesion molecules belonging to the cadherin family of cell adhesion substances and are very important in keeping the covering of our skin together.
A recent innovation has been the introduction of an antigen specific ELISA test in the diagnosis of pemphigus. The patient’s serum is tested on ELISA plates pre-coated with recombinant proteins of the ectodomain of Dsg1 or Dsg3 antigens (Medical and Biological laboratories Co, Ltd, Nagoya, Japan). Thus specific antibodies directed against Dsg1 or Dsg3 antigens can be detected by this technique.
It was seen that 61% of patients with PV have antibodies to Dsg 1 in addition to Dsg3, and presence of both the antibody types was associated with severe cutaneous and mucosal involvement, while presence of only Dsg3 autoantibodies was associated with pemphigus limited to mucosal surfaces (mainly oral). The proportion of Dsg1 positive PV patients was higher in the Asian ethnic group when compared to their British counterparts. The severity of the skin and oral disease is influenced by the quantities of Dsg1 and Dsg3 antibodies present in a patient.
Whether ELISA plate techniques will eventually overtake immunofluoresence in the diagnosis of pemphigus and related diseases is too early to say, but they are an important advance and enable large numbers of samples to be read quite quickly. I am sure those of you who are interested in pemphigus will see much more on this in the future about diagnostic techniques. Clearly, accurate diagnosis will ultimately lead to the potential of good targeted therapies.