|Year : 2018 | Volume
| Issue : 1 | Page : 26-30
Oral pemphigus vulgaris: A case series and review of literature
Bhavana Gupta1, Vivek Gupta2
1 Department of Oral Pathology, Dental Institute, RIMS, Ranchi, Jharkhand, India
2 Department of Periodontology, Dental Institute, RIMS, Ranchi, Jharkhand, India
|Date of Web Publication||14-May-2018|
Dr. Bhavana Gupta
C-2/600, Sector C, Jankipuram, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Pemphigus vulgaris (PV) is an autoimmune disease, normally associated with oral lesions that generally affects patients aged 40–60 years. PV manifests as extremely painful and persistent oral lesions. Here, we present a case series of PV (one male and two female patients with age between 35 and 50 years). It is an attempt to highlight its importance in diagnosis along with the review of literature on its molecular aspect.
Keywords: Autoimmune diseases, bullae, mucous membrane, pemphigus vulgaris
|How to cite this article:|
Gupta B, Gupta V. Oral pemphigus vulgaris: A case series and review of literature. J Dent Res Rev 2018;5:26-30
| Introduction|| |
The term “Pemphigus” is derived from the Greek word pemphix(bubbles, blisters) and “Vulgaris” is derived from the Latin word which means “common.” Pemphigus vulgaris (PV) was named by Wickman in 1791. PV is the most frequently observed member of a group of chronic autoimmune mucocutaneous diseases characterized by the formation of intraepithelial blisters. It is a rare disease (0.1–0.5 cases/100,000 inhabitants/years), with onset in the fifth or sixth decade of life. It is a group of potentially life-threatening autoimmune disease and is classified into six types: PV, pemphigus erythematosus, pemphigus vegetans, pemphigus foliaceus, paraneoplastic pemphigus, and IgA pemphigus.,
Herein, we report a case series of PV and the review the literature for establishing the clinicopathologic characteristics of PV.
| Case Reports|| |
A 45-year-old female patient came to the Department of Oral Medicine and Radiology, with a history of painful ulcers for 3 months. The patient reported that the lesions caused discomfort and affected the normal function. There was no significant personal and family history. On intraoral examination, ulcers were found in the right and left buccal mucosa, labial mucosa, and palate [Figure 1]. No skin lesions are seen in extraoral examination. The provisional diagnosis of pemphigus and pemphigoid was made. The differential diagnosis of acute herpetic stomatitis and recurrent aphthous stomatitis was suggested. Biopsy was done, and the tissue was sent for histopathological examination. The oral tissue biopsies were taken from the perilesional site.
|Figure 1: The intraoral photograph of the first patient showing lesions present on bilateral buccal mucosa along with on palate and labial mucosa|
Click here to view
[Figure 2] shows gross tissue with suture thread postbiopsy. The low-power magnification (×100) shows stratified squamous epithelium with a suprabasilar cleft. The connective tissue is moderately dense. The high-power magnification (×400) shows parakeratinized stratified squamous epithelium with spongiosis. The epithelium exhibits suprabasilar cleft. The arrow shows Tzanck cells. The final diagnosis of PV was made.
|Figure 2: The photograph showing gross specimen of the lesional tissue along with photomicrograph showing suprabasal epithelial clefts in ×100 and ×400. The arrow showing completely detached keratinocytes (acantholytic cells)|
Click here to view
The patient was given Wysolone 10 mg thrice a week, later tapering doses was done, twice a week to once a week. For topical application, Tubocort ointment was given to the patient and was recalled after 15 days. After 15 days, no new lesions appeared, and left and right buccal mucosa showed improvement in healing process.
A 32-year-old male patient came to the Department of Oral Medicine and Radiology, with a history of painful ulcers and bleeding gums for 2–3 months. The patient reported that the lesions caused discomfort and affected the normal function. There was no significant medical history. On intraoral examination [Figure 3], the lesions were noted on the left buccal mucosa and on marginal gingiva on buccal and lingual surface. A biopsy was obtained from a perilesional site under local anesthesia and was sent for routine histopathological examination. The grossing of the tissue was done, and later, histopathological examination was done after tissue processing and routine hematoxylin and eosin (H and E) staining.
|Figure 3: The intraoral photograph of the second patient showing lesions in buccal mucosa, labial, and lingual marginal gingival along with the gross specimen of the lesional tissue|
Click here to view
The histopathological examination
[Figure 4] revealed stratified squamous epithelium with suprabasilar spilt. The fibrous connective tissue is moderately dense. The arrow shows that the basal cell layer had a characteristic “tombstone” appearance. The epithelium also showed spongiosis with acantholysis. Tzanck cells and focal influx of neutrophils and lymphocytes can be appreciated (H and E stain, ×200).
|Figure 4: The photomicrograph showing suprabasal epithelial clefts in × 100. The arrow shows acantholytic cells between the split|
Click here to view
The patient was advised complete oral prophylaxis and tapering doses of Wysolone 10 mg for 3 weeks and was recalled after 15 days. Slight improvement in marginal gingival of labial and lingual surfaces was appreciated.
A 42-year-old female patient was referred to the Department of Oral Medicine and Radiology, with a history of painful ulcers and inability to chew food from right sides for 4 months. There was no significant personal and family history. On intraoral examination, ulcers were seen in the right mucosa [Figure 5]. No skin lesions are seen in extraoral examination.
|Figure 5: Intraoral photograph of the third patient showing lesion (flaccid bullae) present on the left buccal mucosa along the line of occlusion; the photomicrograph shows suprabasal epithelial split in the epithelium|
Click here to view
Oral tissue biopsies were taken from the periphery of the lesions. The tissue was fixed in formalin and embedded in paraffin. Sections were stained with H and E and examined using light microscope. Histopathologically, the lesions showed intraepidermal blister, loss of intercellular attachments resulting in acantholysis, and dermal inflammatory infiltrate. Suprabasal epithelial clefts were detected. Inside the cleft, partially and completely detached keratinocytes (acantholytic cells) from the basal and lower prickle cells layers were spotted as single cells or clusters. In addition, lymphocytes and neutrophils were the main inflammatory cells inside the cleft. In all tissue sections, the superficial parts of the connective tissue were characterized by edema, small blood vessels, loose collagen fiber arrangement, and both interstitial and perivascular inflammatory infiltrates were evident.
The patient was advised topical corticosteroid Turbocort, triamcinolone acetonide for 15 days, and was called after 15 days. Slight improvement in the lesions was seen.
| Discussion|| |
Pemphigus is defined as a group of disorders with autoimmune etiology which could be life threatening and clinical manifestations are mainly epithelial blistering affecting cutaneous and/or mucosal surfaces including mucosa of the mouth, nose, conjunctiva, genitals, esophagus, pharynx, and larynx., Although certain pathogenesis of pemphigus is not totally understood, high frequency of pemphigus in some races, especially Ashkenazi Jews and Mediterranean and South Asian origin, has been shown to be actually related to HLA-II genes., Any localization of oral mucosa may be affected; however, sites of trauma such as buccal mucosa, gingiva, and palate are especially affected.,, In pemphigus, the antibodies are produced against desmosomes (adhesive protein), especially main antigen in PV is desmoglein (Dsg) 3, a protein constituent of the desmosomes. Most patients with PV have circulating IgG autoantibodies against Dsg3. These antibodies bind to the Dsg3 on the epithelial cell membrane and may evoke acantholysis., Another desmoglein is Dsg; it is the target of autoantibodies formation in pemphigus foliaceus. Most patients with oral lesions could be initially misdiagnosed, usually as aphthous stomatitis, gingivostomatitis, erythema multiforme, erosive lichen planus, or oral candidiasis, and may be improperly treated for months or years. The diagram shows the mode of action how pemphigus affects skin and oral mucous membrane.
Differential diagnosis of pemphigus vulgaris,,,,,,,,
- Recurrent aphthous stomatitis – Appearance of ulcers (aphthae) in oral mucosa with yellowish base, surrounded by an erythematous halo and regular margins and that disappear without treatment
- Behçet's disease – Appearance of aphthae in the oral mucosa with genital and ocular ulcers
- Erythema multiforme – Target-shaped skin lesions, oral erosions, involvement of lips in the form of erosions and crusts
- Erosive lichen planus – Appearance of Wickham striae and erosive lesions
- Acute herpetic gingivostomatitis – Prodromic symptoms followed by the onset of small yellowish vesicles that rapidly rupture, giving rise to ulcers with an erythematous halo. It affects free and attached gingiva
- Impetigo – Bacterial infection with appearance of skin ulcers covered by a honey-colored crust. It affects face, arms, and legs. It is more frequent in children
- Disease by linear IgA deposit – Symmetric blisters and pruritic lesions, target-shaped lesions
- Mucosal pemphigoid or cicatricial pemphigoid – Possible manifestation of an underlying malignant disease: oral lesions do not precede skin lesions, and blisters are smaller with a shorter duration than in PV. They heal rapidly without scarring
- Bullous pemphigus – Vesicles or tension blisters with clear content that develop on normal or erythematous skin; intense pruritus, symmetric lesions that appear on flexion areas, root of extremities, thighs, and abdomen; rare on mucosae
- Herpetiform dermatitis – 1–3 cm erythemas that infiltrate palate and buccal mucosa; aphthae on labial mucosa. They appear months or years after the appearance of lesions on skin
- Epidermolysis bullosa – Development of blisters with minimal pressure, ring-shaped atrophic scars on the inner surface of limbs, and articulations
- Paraneoplastic pemphigus – Autoimmune syndrome associated with lymphoproliferative neoplasm of B cells
- There is no oral lesions seen in Erythematous pemphigus and Pemphigus foliaceus
- Chronic benign pemphigus familiaris – There are usually no oral lesions
- Disseminated lupus erythematosus – Systemic signs (fever, asthenia) normally accompanied by petechiae, edemas, and dry mouth
- Crohn's disease and hemorrhagic rectal colitis – Mucocutaneous signs accompanied by abdominal pain, aphthae in oral mucosa, asthenia, weight loss, and anorexia
- Folic acid or Vitamin B12 deficiency – Oral pain, erythematous tongue, asthenia and anemia, paresthesias in limbs, and physical problems hypochromic iron deficiency pallor, fatigue, cephalalgias, vertigo, buzzing in the ears, irritability, insomnia, concentration problems, sensitivity to cold, anorexia, and nausea
- Enteropathic acrodermatitis – loss of taste and smell, sight problems, intense diarrhea, alopecia, and hypertension.
Without proper investigation and treatment plan, pemphigus can be a fatal disease because there is loss of the epidermal barrier function, leading to loss of body fluids and secondary bacterial infection. Although the principal mean of treatment is systemic corticosteroid therapy, with or without so-called “steroid-sparing” immune suppressants, other immunomodulating drugs “intravenous” Igs, monoclonal antibody therapy directed against B-lymphocytes, have been used for effective therapy if the condition does not respond to systemic corticosteroids or if the patient cannot tolerate the side effects of this treatment. The diagrammatic representation [Figure 6] of the layers of epithelium showing how pemphigus occurs in skin amd mucous membrane. The red and green markers are IgG anti desmoglein (Dsg 1) and are IgG anti desmoglein (Dsg 3). Label A shows mucous e pemphigus, which is caused by the action of IgG anti Dsg 3 at the supra basal level of mucous membrane. Label B shows muco cutaneous pemphigus vulgaris, which is caused by both IgG anti Dsg1 and IgG anti Dsg3. Label C shows pemphigus foliaceus which is caused by the action by IgG anti Dsg1. Label D, E, F shows Pemphigus occurring in skin.
|Figure 6: The red and green markers are IgG anti desmoglein (Dsg 1) and are IgG anti desmoglein (Dsg 3). (A) Mucous e pemphigus, which is caused by the action of IgG anti Dsg 3 at the supra basal level of mucous membrane, (B) Muco cutaneous pemphigus vulgaris, which is caused by both IgG anti Dsg1 and IgG anti Dsg3, (C) Pemphigus foliaceus which is caused by the action by IgG anti Dsg1, (D-F) Pemphigus occurring in skin|
Click here to view
| Conclusion|| |
Pemphigus is primarily considered to be a dermatologic disease. The fact that PV commonly and initially affects the oral mucosa and then the skin gives dentists a great opportunity to detect the disease at an early stage. There needs to be a great collaboration efforts between dermatologists and dentists which would provide better treatment and avoid serious sequelae and death of the patients. Newer diagnostic tests have been undertaken to check the role of anti-Dsg antibodies – keratinocytes binding in formation of blisters which are prevalent in the body of the pemphigus patients. The treatment goals include suppression of circulating autoantibodies with the usage of systemic corticosteroids and newer adjuvant. Clinical examination along with other diagnostic modalities such as routine biopsy and direct and indirect immunofluorescence helps in differentiating the disease from the other bullous lesions.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Rajendran R, Sivapathasundharam B. Shafer's Oral Pathology. 6th
ed. New Delhi: Elsevier; 2009.
Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial Pathology. 3rd ed. Philadelphia: Saunders; 2009.
Rath SK, Reenesh M. Gingival pemphigus vulgaris preceding cutaneous lesion: A rare case report. J Indian Soc Periodontol 2012;16:588-91.
] [Full text]
Scully C, Challacombe SJ. Pemphigus vulgaris: Update on etiopathogenesis, oral manifestations, and management. Crit Rev Oral Biol Med 2002;13:397-408.
Salmanpour R, Shahkar H, Namazi MR, Rahman-Shenas MR. Epidemiology of pemphigus in South-Western Iran: A 10-year retrospective study (1991-2000). Int J Dermatol 2006;45:103-5.
Mignogna MD, Fortuna G, Leuci S. Oral pemphigus. Minerva Stomatol 2009;58:501-18.
V'lckova-Laskoska MT, Laskoski DS, Kamberova S, Caca-Biljanovska N, Volckova N. Epidemiology of pemphigus in Macedonia: A 15-year retrospective study (1990-2004). Int J Dermatol 2007;46:253-8.
Scully C, Paes De Almeida O, Porter SR, Gilkes JJ. Pemphigus vulgaris: The manifestations and long-term management of 55 patients with oral lesions. Br J Dermatol 1999;140:84-9.
Ruocco V, Ruocco E, Lo Schiavo A, Brunetti G, Guerrera LP, Wolf R, et al.
Pemphigus: Etiology, pathogenesis, and inducing or triggering factors: Facts and controversies. Clin Dermatol 2013;31:374-81.
Ruocco E, Wolf R, Ruocco V, Brunetti G, Romano F, Lo Schiavo A, et al.
Pemphigus: Associations and management guidelines: Facts and controversies. Clin Dermatol 2013;31:382-90.
Fassaman A, Vanek J. Manifestation of pemphigus vulgaris in the orofacial region. A case report script. Medica 2003;76:55-62.
Fainaru O, Mashiach R, Kupferminc M, Shenhav M, Pauzner D, Lessing JB, et al.
Pemphigus vulgaris in pregnancy: A case report and review of literature. Hum Reprod 2000;15:1195-7.
Kapoor S, Sikka P, Kaur GP. Pemphigus vulgaris of oral cavity: A case report with its management strategies. Int J Nutr Pharmacol Neurol Dis 2013;3:2. [Full text]
Lanza A, Cirillo N, Femiano F, Gombos F. How does acantholysis occur in pemphigus vulgaris: A critical review. J Cutan Pathol 2006;33:401-12.
Mihai S, Sitaru C. Immunopathology and molecular diagnosis of autoimmune bullous diseases. J Cell Mol Med 2007;11:462-81.
Sitaru C, Zillikens D. Mechanisms of blister induction by autoantibodies. Exp Dermatol 2005;14:861-75.
Hertl M, Eming R, Veldman C. T cell control in autoimmune bullous skin disorders. J Clin Invest 2006;116:1159-66.
Tsuruta D, Ishii N, Hamada T, Ohyama B, Fukuda S, Koga H, et al.
IgA pemphigus. Clin Dermatol 2011;29:437-42.
Kneisel A, Hertl M. Autoimmune bullous skin diseases. Part 1: Clinical manifestations. J Dtsch Dermatol Ges 2011;9:844-56.
Meyer N, Misery L. Geoepidemiologic considerations of auto-immune pemphigus. Autoimmun Rev 2010;9:A379-82.
Hans-Filho G, dos Santos V, Katayama JH, Aoki V, Rivitti EA, Sampaio SA, et al.
An active focus of high prevalence of fogo selvagem on an Amerindian reservation in Brazil. Cooperative Group on Fogo Selvagem Research. J Invest Dermatol 1996;107:68-75.
Rocha-Alvarez R, Ortega-Loayza AG, Friedman H, Campbell I, Aoki V, Rivitti EA, et al.
Endemic pemphigus vulgaris. Arch Dermatol 2007;143:895-9.
Joly P, Litrowski N. Pemphigus group (vulgaris, vegetans, foliaceus, herpetiformis, brasiliensis). Clin Dermatol 2011;29:432-6.
James KA, Culton DA, Diaz LA. Diagnosis and clinical features of pemphigus foliaceus. Dermatol Clin 2011;29:405-12, viii.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]