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Punctate pemphigus: an underreported direct immunofluorescence pattern

To the Editor , We read with interest the recent manuscript by Ko and McNiff regarding the ‘punctate’ immunofluorescence pattern of pemphigus.1 The authors describe an IgG deposition pattern in pemphigus patients and emphasize their observation of a dotted or partly dotted pattern. We agree with the authors that such patterns are regularly seen in biopsies of pemphigus patients, and we are obliged to them for raising awareness of these distinctive immunofluorescence patterns, which indeed are not mentioned in the majority of the textbooks. In their discussion, the authors try to explain this punctate pattern of IgG deposition as follows: ‘Perhaps in vivo, the dot-like immunofluorescence pattern corresponds to increased distance between desmoglein containing desmosomes, with less confluence of the immuno fluorescence signal, particularly in cases where interdesmosomal desmoglein 1 is absent’. In our opinion, there is a different explanation for this pattern. In 2011, we demonstrated that in patients with antibodies to desmoglein 3, these dots consist of IgG, desmoglein 3 and some plakoglobin, while other desmosomal components are absent.2 Similarly, in patients with antibodies to desmoglein 1, the dots contain IgG, desmoglein 1 and plakoglobin, but again no other desmosomal components are present. Due to its bivalency, the IgG crosslinks the non-junctional desmoglein molecules, and these crosslinked molecules then concentrate in dots. Targeted desmoglein cannot be incorporated in desmosomes, thereby leading to selectively desmoglein-depleted desmosomes. Such desmosomes remain functional as long as either non-junctional desmoglein 1 or desmoglein 3 is available for incorporation. If neither is available, desmosomes will not form with acantholysis as a consequence. This is why patients with anti-desmoglein 3 antibodies have blistering at the suprabasal level of the mucosa, where desmoglein 1 is not expressed, while in contrast patients with anti-desmoglein 1 antibodies have superficial skin blisters, where desmoglein 3 is not expressed. It is important to realize that clustering itself is not pathogenic but only reflects the residual ‘garbage’ of desmoglein targeted by bivalent IgG. Other proof that the punctate pattern is not caused by increased distance between desmosomes is that in skin of patients with mucosa-dominant pemphigus vulgaris, the IgG deposition pattern is limited to a few clusters per cell, while the number of desmosomes does not change compared with normal human skin.3 In conclusion, we agree with the authors that a punctate or granular epidermal cell surface pattern is regularly seen in pemphigus. However, we believe the explanation must be found in selective crosslinking and aggregation of IgG and its targeted autoantigen.