Distinguishing pustular psoriasis and acute generalized exanthematous pustulosis on the basis of plasmacytoid dendritic cells and MxA protein

Abstract

Background Distinguishing acute generalized exanthematous pustulosis (AGEP) and pustular psoriasis (PS) can be challenging. Staining for plasmacytoid dendritic cells, or PDCs (producer of IFN‐α/β), and MxA (an IFN‐α/β inducible protein) may help discriminate these entities. Methods Forty‐three cases of AGEP and PS were compiled from two academic institutions. All cases were examined for CD123+ PDCs, eosinophils, acanthosis, papillomatosis, suprapapillary plate thinning, tortuous dilated capillaries, single necrotic keratinocytes, papillary dermal edema, vasculitis, eosinophil exocytosis, intraepidermal pustules, and subcorneal pustules. A subset of cases (n = 26) was stained for MxA. Results Perivascular and intraepidermal PDCs, dilated tortuous vessels, and MxA expression in the dermal inflammatory infiltrate were significantly (P < 0.05) in favor of a diagnosis of PS. The absence of PDCs and presence of eosinophils favored a diagnosis of AGEP (P < 0.05). Conclusions We found compelling evidence for the use of CD123 to highlight PDCs in these cases. The presence of PDCs and expression of MxA in dermal inflammatory infiltrate, as well as absence of eosinophils and presence of tortuous dilated capillaries favored a diagnosis of PS. Expression of MxA in the dermal infiltrate corresponds with a Th1 pathway in PS and may indicate a Th1 component in the early initial phase of AGEP.

Plasmacytoid dendritic cells in keratoacanthoma and squamous cell carcinoma: A blinded study of CD123 as a diagnostic marker

“…However we were unable to reject our prespecified null hypothesis of no difference in CD123 staining in KA and SCC. Our results are contrary to most published diagnostic accuracy studies on CD123 in, which investigators have usually found CD123 immunostaining to improve diagnostic accuracy in a broad range of differential diagnoses . Previous studies that have found CD123 efficacious for differential diagnosis rarely describe blinding the test rater.…”

“…CD123 is a sensitive and specific marker of PDCs with multiple commercially available clones approved for in vitro diagnosis . It has been used in descriptive observational studies to identify PDCs in diseases and in diagnostic accuracy studies as a test to differentiate between diseases …”

Diagnostic utility of plasmacytoid dendritic cells in dermatopathology

“…While different studies had some variation in the systems used to immunohistochemically evaluate the presence of plasmacytoid dendritic cells (mainly by using CD123 or blood-derived dendritic cell antigen-2) and/or their product type I interferon (using myxovirus resistance protein A), they generally had in common the evaluation of plasmacytoid dendritic cell content, clustering and distribution. [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] For plasmacytoid dendritic cell content, semi-quantitative scoring systems that evaluate plasmacytoid dendritic cells as a percentage of the total mononuclear infiltrate were more commonly used than absolute plasmacytoid dendritic cell counts in most of the studies. 11,12,[15][16][17][33][34][35][36] Plasmacytoid dendritic cell clusters were defined differently among studies, varying from clusters of at least 5 touching plasmacytoid dendritic cells, 23 ≥10 plasmacytoid dendritic cells, [15][16][17]25,26,30 ≥15 touching CD123 + plasmacytoid dendritic cells 28 to 20 or more cells.…”

“…Acute generalized exanthematous pustulosis is a reaction pattern that most commonly occurs secondary to medications. 36…”

“…diagnosis of pustular psoriasis, whereas the absence of plasmacytoid dendritic cells and presence of eosinophils significantly favored a diagnosis of acute generalized exanthematous pustulosis 36. …”