Pemphigus vulgaris. A presentation of 14 cases and review of the literature
Pénfigo vulgar. Presentación de catorce casos y revisión de la literatura

Fabio Camacho Alonso ⁽¹⁾, Pía López Jornet ⁽²⁾, Ambrosio Bermejo Fenoll ⁽³⁾

(1) Máster de Cirugía e Implantología Bucal por la Universidad de Valencia. Profesor colaborador de Medicina Bucal
(2) Profesora titular de Medicina Bucal
(3) Catedrático de Medicina Bucal. Facultad de Medicina y Odontología. Universidad de Murcia

Address:
Dr. Fabio Camacho Alonso
Clínica Odontológica Universitaria
Hospital Morales Meseguer
Adv. Marques de los velez s/n
Murcia 30008
Email: fabiosurgery@hotmail.com

Received: 6-06-2004 Accepted: 12-03-2005 

INTRODUCTION

The term pemphigus is used to describe a group of infrequent ampullar mucocutaneous diseases presenting an underlying autoimmune mechanism and a chronic course with unpredictable activity outbreaks. Pemphigus is characterized by the appearance of acantholytic intraepithelial blisters, and in some cases can prove life-threatening. Although pemphigus vulgaris (PV) is the most common form of the disease, it is infrequent – with a reported incidence of 0.1-0.5 cases per 100,000 inhabitants and year (1). PV affects both sexes equally, though some authors (2,3) have reported a greater incidence among women. The disease is most prevalent between the fourth and sixth decades of life, though juvenile cases are sometimes observed (4).

PV is the form of pemphigus that most frequently affects the oral mucosa, and in most cases (75%) the oral lesions precede the cutaneous manifestations (5). The course is chronic, and systemic involvement may occur if adequate treatment is not provided. Indeed, prior to the introduction of corticotherapy, these diseases often proved fatal (5-7).

The fact that blisters on the oral mucosa are sometimes the first manifestation of the disease implies that dental professionals must be sufficiently familiarized with the clinical manifestations of PV to ensure early diagnosis and treatment. The present study describes our experience with 14 cases of PV, and compares the results obtained with those reported in the literature.

CLINICAL CASES

Fourteen Caucasian patients (10 women and 4 men, aged 21-87 years) with PV were seen in the Teaching Unit of Oral Medicine of the University of Murcia Medical and Dental School (Spain) between 1981 and 2001. All presented blisters, erosions and/or ulcers on the oral mucosa. In no case had the lesions been present for more than 6 years at the time of the first visit. Patient age and sex was recorded in all cases, together with the clinical and pharmacological treatment history, the clinical presentation (presence or absence of ulceration), symptoms, lesion location within the oral cavity, their extent within the mouth, and the presence or absence of bilaterality. Lesion extent was rated by three consecutive grades as follows: grade 1 (only one affected location in the mouth), grade 2 (two affected locations), and grade 3 (three or more locations). Oral symptoms were in turn classified as follows: 1 =asymptomatic, 2 = nonspecific discomfort, and 3 = pain. The involvement or not of skin and/or other mucosal membranes was also documented.

In all cases we recorded different hematological parameters (including blood chemistry), and a biopsy was obtained of the intraoral lesions. The specimen sections were stained with hematoxylin-eosin, and the principal histological characteristics were evaluated. Direct immunofluorescence studies were carried out in two cases. Lastly, the treatment provided in each case was recorded, along with its efficacy in reducing the lesions.

Table 1 shows the main clinical characteristics of each patient. In our series of 14 patients the mean age was 44.78 years (range 21-87), with a clear female predominance (10 out of 14 cases). The mean duration of the intraoral lesions at the time of treatment was 11.66 months (range 0.75-72), with no full remission during this time in any subject. None of the patient presented associated disorders or factors of interest. All subjects presented intraoral ulcerations that caused nonspecific discomfort in 9 cases, no symptoms in one patient, and pain in four. The lesions failed to resolve for several weeks (Fig.s 1 and 2). The hematological parameters and blood chemistry were within the normal range in all cases. The histological study of the biopsies (Fig. 3) showed the presence of intraepithelial blisters, with acantholytic cells and eosinophilic spongiosis in all cases. Direct immunofluorescence testing was carried out in two patients, and proved positive for intercellular IgG and IgM deposits in both subjects, and also C₃-positive in one.

Topical corticoids (0.5% triamcinolone acetonide) were administered. Since all cases presented lesions in different locations within the oral cavity, we decided to administer the corticoids as an oral suspension, three times a day. In 12 cases this treatment was combined with systemic prednisone (60 mg a day during one month), while in one patient intralesional corticoid infiltration was added (in the form of parametasone 1 cm³ every 15 days during 45 days). All patients responded to treatment, with important lesion improvement at the end of therapy. Due to the good response recorded in this series of patients, no immunosuppressive therapy proved necessary.

DISCUSSION

Pemphigus vulgaris (PV) is a chronic vesicular-ampullar and erosive disease that may lead to systemic involvement. Although the disorder is first recognized from its skin lesions, other locations such as the gums, oral mucosa and other mucosal membranes (including the vaginal cavity) can also be affected (8). In most cases (75%), the oral lesions are the first manifestation of the disease (5).

While the precise etiology of PV is not clear, it is known to involve an autoimmune mechanism with antibodies that alter the epithelial intercellular junctions (9,10). These antibodies have been shown to be targeted to desmogleins – a subfamily of cellular adhesion molecules found within the desmosomes. PV can also involve genetic factors, since certain ethnic groups (e.g., Jews and Mediterranean populations) are particularly susceptible to PV. In addition, the literature describes familial cases, and a certain relation to antigens of the major histocompatibility complex (MHC)(11-13).

Pemphigus can also be drug-induced (14). In effect, any drug substance containing an active –thyl group in its molecular structure is considered to be able to give rise to the disorder (14). Some known PV-inducing agents are the sulfonamides, penicillins and antiepileptic drugs. In our series of 14 patients we registered the pharmacological treatment history of all subjects, though none were seen to have used any of these drugs. It has also been suggested that members of the botanical family Allium, including onions, leeks and garlic can induce pemphigus lesions (15).

PV affects both men and women equally (6). Most patients develop the symptoms in the fourth to fifth decades of life, though juvenile cases have also been reported (4). In our series the mean patient age was 44.78 years, and women predominated over men (10 out of 14 cases).

Regarding the clinical manifestations, approximately 75% of all cases of PV initially manifest in the oral mucosa (5). The lesions at first comprise small asymptomatic blisters, though these are very thin-walled and easily rupture – giving rise to painful and hemorrhagic erosions. While the lesions can be located anywhere within the oral cavity, they are most often found in areas subjected to friction trauma, such as the cheek mucosa, tongue, palate and lower lip (2). In all our cases the oral lesions were the first manifestation of the disease, in the form of blisters and/or ulcers that caused nonspecific discomfort. Pain was only reported in four cases. The lesions may persist within the mouth for a number of months before progressing to the skin and other mucosal membranes – including the nose, pharynx, larynx, esophagus, vulva, penis or anus (7). In our series 6 patients also had extraoral lesions (Table 1).(16)

The diagnostic orientation is provided by the clinical oral manifestations, while confirmation is provided by the histological biopsy study, which shows the presence of intraepithelial blisters, acantholysis and Tzanck cells. Direct immunofluorescence evaluation of fresh lesion specimens reveals IgG or IgM and complement fragments in the intercellular space (9). All our cases were histologically confirmed, with positive direct immunofluorescence findings in the two cases in which the technique was carried out. A differential diagnosis must be established with the rest of vesicular-ampullar diseases.

The treatment of pemphigus is designed to inhibit production of the aggressor antibodies (17). This is normally achieved by administering moderate corticoid doses via the oral route (18). Immunosuppressors such as cyclosporine or cyclophosphamide can also be prescribed (17). We applied topical corticoids to all our patients, together with systemic corticoids in 12 subjects and intralesional corticoids in one patient – with satisfactory results in all cases.

To summarize, pemphigus vulgaris is a chronic autoimmune mucocutaneous disease that often initially manifests in the form of intraoral lesions that posteriorly spread to the skin and other mucosal membranes. Consequently, dental professionals must be sufficiently familiarized with the clinical manifestations of PV to ensure early diagnosis and treatment, since this in turn determines the prognosis and course of the disease.

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