Serodiagnosis of paraneoplastic pemphigus

Paraneoplastic pemphigus (PNP) is a rare but severe autoimmune disease characterized by diverse mucocutaneous lesions in association with an underlying neoplasm. Patients have an unique humoral response, with circulating autoantibodies directed against plakins, desmogleins, and against alpha-2 macroglobulin-like 1 protein (A2ML1). The clinical and histological manifestations show much overlap with other dermatological conditions. The diagnosis of PNP therefore largely relies on the demonstration of the specific PNP autoantibodies in serum. There are several techniques available to do this, including radioactive immunoprecipitation (IP), non-radioactive IP combined with immunoblot (IB), envoplakin-ELISA, and indirect immunofluorescence (IIF) on rat bladder urothelium. In a recent study, we compared the sensitivities and specificities of these techniques for PNP, using sera of 19 PNP patients and 40 control patients. The control patients included patients with pemphigus vulgaris and toxic epidermal necrolysis (TEN). Our results showed that the detection of anti-envoplakin and -periplakin antibodies are most sensitive and specific for PNP. In addition, anti-A2ML1 antibodies were present in 79% of our PNP sera, but also, albeit in lower titers, in 4 out of 13 TEN sera. The demonstration of anti-envoplakin and -periplakin or - A2ML1 antibodies using radioactive IP or IP-IB was most sensitive (95% and 100%, respectively) and highly specific (100% and 86%, respectively) to confirm the diagnosis PNP. A combination of IIF on rat bladder and IB also had a sensitivity and specificity of 100%, and is faster and easier to perform than IP. This combination should therefore be used as first step in the sero-diagnosis of PNP.</p

Hidradenitis suppurativa:The third cause of vulva carcinoma

The development of squamous cell carcinoma (SCC) is a severe complication of chronic HS (HS). HS associated SCC can present as a painful, persistent tumour or ulcer without typical HS characteristics such as sinus formation and inflammation. Especially male patients with prolonged HS in extra-axillary areas are at risk for this complication. This case of HS associated vulvar SCC emphasizes that also women can develop this complication. In addition to lichen sclerosus vulvae (via dVIN) and high risk HPV (via uVIN) there is a third disease that can lead to vulvar cancer; chronic HS. The clinician should be vigilant for the development of malignant transformation in cases of severe, chronic HS, and should have a low threshold for biopsy. Staging, therapy and follow-up should be performed by gynecologic oncologists in an academic center.</p

Paraneoplastic pemphigus with fatal bronchiolitis obliterans

Paraneoplastic pemphigus (PNP) is a rare autoimmune bullous disease, associated with high mortality and morbidity. Accurate serological tools exist to confirm its diagnosis, providing the clinician considers this diagnosis. We present a case of a young woman with a painful stomatitis, which had been treated, prior to presentation at our clinic as erosive lichen planus. Additional serological tests led to the diagnosis paraneoplastisch pemphigus (PNP), which lead to further oncological screening. An intra-abdominal follicular dendritic cell sarcoma was found. Despite surgical removal of the sarcoma and treatment with high dose systemic corticosteroids, rituximab, and intraveneous immunoglobulins, the stomatitis persisted and the patient developed a bronchiolitis obliterans from which she died, six months after the diagnosis . This case illustrates the fulminant path that PNP can follow , and calls for further studies aimed at identifying the risk factors and optimal therapeutic regimens for bronchiolitis obliterans and PNP.</p