Diagnosis of Oral Pemphigus Vulgaris: from histological studies to new serological methods
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1
University of Turin, Department of Surgical Sciences - Oral Medicine Section, Italy
Aim. Pemphigus is a rare autoimmune disease, with an incidence of 0.5-3.2/100.000 per year, mostly diagnosed between 50 and 60 years old, rare among children, with equal distribution between males and females. Pemphigus Vulgaris (PV) is the most frequent subtype of pemphigus, representing 80% of all cases, with primary involvement of the oral cavity. The diagnosis of PV requires a proper anamnesis together with a complete clinical, histological and immunological examination. Direct immunofluorescence (DIF) is considered the gold standard for diagnosis, searching IgG, IgM, IgA autoantibodies and C3 fraction and revealing IgG deposits commonly distributed in a “fish-net” appearance in the intercellular spaces. However, it is important to remind that such approach relies upon an invasive procedure, whose success rate is linked to the surgical skills of the oral physician. On the other hand, the quantitative search of serum anti-desmoglein (DSG) 1 and 3 autoantibodies requires the acquisition of a blood sample, which may be labeled as a noninvasive procedure, easier to perform than an incisional biopsy.
Aim of this study was to evaluate the reliability of anti-DSG-1/3 autoantibodies in the diagnosis of oral PV, using DIF as the gold standard and term of comparison, in order to speculate about the possibility of avoiding biopsy sampling.
Materials and Methods. The medical case records of 33 patients with proper diagnosis of PV referring to the Oral Medicine Section, CIR- Dental School in Turin, Italy were analyzed.
Inclusion criteria were: patients with histopathological diagnosis of PV, obtained through Hematoxylin & Eosin staining and DIF who also underwent serological identification of anti-DSG1 and 3 autoantibodies within six months since the specimen analysis.
Out of 33 patients, such strict inclusion criteria led to the recruitment of 8 patients: 3 males (37.5%) and 5 females (62.5%), aged between 37 and 84 (mean age 55.2). Regarding the examined parameters, IgA, IgM, IgG and C3 positivity detected through DIF were scored between 0 and 3, based on the degree of positivity (+, ++, +++, respectively). Histologically, fissures, acantholytic keratinocytes, stromal oedema and infiltration nodes were scrutinized and we assigned a score of “1”, when present, and “0”, if not detected.
Results. DIF analysis revealed no IgA and IgM positivity, while IgG were detected in each patient, with a high positivity (+++) in 50% (4 out of 8) of the samples. In 62.5% of the samples (5 out of 8), a slight positivity (+) for C3 was displayed.
Histological examination highlighted the coexistence of fissures, stromal oedema and acantholysis in 62.5% of the samples (5 out of 8). Serological examination showed 87.5% (7 out of 8) positivity to anti-DSG3, of which one patient was positive to both anti-DSG1 and anti-DSG3. Concerning the strength of association between DIF-mediated IgG positivity and anti-DSG3 titres, 5 out of 8 (62,5%) patients with moderate/high (++/+++) positivity to IgG showed, at the same time, high titres of anti-DSG3 antibodies (range between 145 and 274 U/ml). On the other hand, 2 out of 8 (25%) patients showed high titres of anti-DSG3 antibodies (134 U/ml and 140,9 U/ml) despite a mild (+) positivity to IgG, whereas one patient (12,5%) showed high positivity (+++) to IgG with anti-DSG3 in range (< 5 U/ml).
Discussion. Our research shows a high but not complete correlation between the degree of positivity to IgG detected through DIF, and the amount of serum anti-DSG autoantibodies: incisional biopsy together with DIF seems to be the most reliable diagnostic tool available, yet. To present, no serological investigation is able to display such a high sensitivity and specificity to replace histopathology analysis. The main limitation of this study is represented by the restricted number of patients enrolled: further studies with larger samples are needed to assess the validity of these preliminary results. A case-control approach is strongly recommended, with anti-DSG 3 quantification to be conducted among PV patients – right after biopsy and DIF - and age-and-sex matched controls, in order to weigh more properly the diagnostic reliability and specificity of anti-DSG3 serum titres.
References
1. Scully C, Challacombe SJ. Pemphigus vulgaris: update on etiopathogenesis, oral manifestations, and management. Crit Rev Oral Biol Med 2002; 13(5): 397-408
2. Ben Lagha, Poulesquen V, Roujeau JC, Alantar A, Maman L. Pemphigus vulgaris: a case-based update. J Can Dent Assoc. 2005 Oct;71(9):667-72
Keywords:
Pemphigus Vulgaris,
Oral diseases,
Desmogleins,
Direct immunofluorescence,
diagnosis
Conference:
5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine., Ancona, Italy, 19 Oct - 20 Oct, 2018.
Presentation Type:
Poster Presentation
Topic:
Oral Diseases
Citation:
Rosso
G,
Digilio
K,
Conrotto
D,
Gambino
A,
Cabras
M and
Carbone
M
(2019). Diagnosis of Oral Pemphigus Vulgaris: from histological studies to new serological methods.
Front. Physiol.
Conference Abstract:
5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine..
doi: 10.3389/conf.fphys.2019.27.00088
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Received:
05 Nov 2018;
Published Online:
09 Dec 2019.
*
Correspondence:
Dr. Giorgia Rosso, University of Turin, Department of Surgical Sciences - Oral Medicine Section, Turin, Piedmont, 10124, Italy, fedemurkez@gmail.com