If I read my horoscope this week, it would no doubt say “Beware of any preconceived notions in your patients with mastocytosis”.
Now that I have expanded my horizons about TMEP, I also need to reconsider the notion that ruling out an autoimmune blistering disease versus bullous cutaneous mastocytosis is straightforward, because the “fact” that direct immunofluorescence (DIF) in patients is always negative is no longer true.
Slavescu et al (Diffuse cutaneous bullous mastocytosis with IgM deposits at dermo-epidermal junction. J Cutan Pathol 2016: 43: 263-9) present a case of a 6 month old female infant with bullous lesions, erythroderma, and a positive Darier sign. A biopsy demonstrated aggregates of mast cells that stained positive with Toluidine blue and CD117 by immunoperoxidase. A DIF was obtained in order to rule out an autoimmune blistering disease such as bullous pemphigoid. DIF microscopy performed on peri-lesional skin revealed granular deposition of IgM at the dermo-epidermal junction (with negative IgG, IgA, and C3). The serum tryptase was elevated, but not to the level to be concerned about systemic mastocytosis (>20ng/ml). Both the bullae and erythrodema regressed with systemic steroids antihistamines.
IgM deposition in DIF may present in different patterns, typically being reported as linear or granular. The granular pattern of IgM has mostly been reported in lupus, but may bee seen in a variety of other inflammatory disorders. The authors state that this is the first report of a positive DIF in a patient with diffuse, bullous mastocytosis.
The mechanism of blister formation in patients (the vast majority being neonates) with mastocytosis is unknown. It is presumed that cytokines and proteases derived from mast cells lyse the basement membrane either directly or via their effect on metalloproteases such as collagenase.
Regardless of the mechanism, it would be easy to understand how a positive DIF in this circumstance could easily be a pitfall allowing a misdiagnosis of a primary blistering disease such as juvenile bullous pemphigoid to be rendered.
The world of absolutes has just gotten smaller. One can no longer say that DIF is always negative in bullous mastocytosis; it is now in the realm of “exceedingly rare”. Don’t let the presence of granular IgM lead you astray in your assessment of bullous disorders in infancy.