We retrospectively reviewed six cases of PV presenting with hemorrhage lip crusting that had been treated at three different institutions in Saudi Arabia and Sweden between 2015 and 2022. Table 1 summarizes the demographics, lip presentation, intraoral lesion sites, histopathological and DIF findings, management and follow-up duration. Informed consent was obtained from all patients, and this study was approved by the Institutional Review Board (IRB), Ministry of Health, Jeddah, Saudi Arabia (approval no. A01372).

A 34-year-old Saudi female patient was referred to the Oral Medicine Clinic at King Fahad General Hospital, Jeddah, Saudi Arabia, by a dermatologist. She complained of pain and a burning sensation in her mouth that started 6 months prior. Regarding her medical history, she had iron-deficiency anemia for 20 years. Accordingly, she took ferrous sulfate (100 mg) and folic acid (1 mg), both once daily. Clinical examination revealed erosions and ulcers in the lower lip, buccal mucosa bilaterally, hard and soft palate, and attached gingivae (Fig. 1a). The patient had skin lesions on the abdomen and right nostril. Our tentative differential diagnoses were PV, mucous membrane pemphigoid, and EM. A 4-mm punch biopsy was taken from the perilesional area of the right buccal mucosa. Histopathological examination using hematoxylin and eosin (H & E) revealed supra-basal acantholysis and a tombstone appearance of the basal cell layer, which was suggestive of PV (Fig. 2a). Subsequently, another incisional biopsy was taken for direct immunofluorescence (DIF) examination, which demonstrated intercellular deposition of IgG. Thus, the diagnosis of PV was confirmed. The patient was started on treatment with prednisolone 1 mg/kg/day (50 mg). Approximately one month after the initiation of steroid therapy, the patient achieved remission of her oral lesions. Thus, gradual steroid tapering (10 mg every 10 days) was started, and azathioprine (AZA) 50 mg once daily was added. The patient continued her treatment with tapering of steroids and AZA. Because the patient was susceptible to developing oral candidiasis during treatment with systemic steroids, nystatin oral suspension 100,000 IU/ml was used as a mouthwash to first treat and then as a prophylactic against oral candidiasis. The total treatment period was nine months. Thereafter, all medications were discontinued, and the patient was free from subjective symptoms and objective signs for fourteen months.

Clinical presentation of lip lesions in cases 1–6 (a-f)

Classic (H&E stain) histopathological findings under 20x magnification for pemphigus vulgaris demonstrate suprabasal clefting, acantholysis and tombstone appearance of the basal cell layer in cases 1–6 (a-f). H&E; hematoxylin and eosin

A 65-year-old Saudi female patient was referred to the Oral Medicine Clinic at King Fahad General Hospital, Jeddah, Saudi Arabia, by a rheumatologist. She complained of ulcers on her tongue and lips. With respect to her medical history, she had developed severe oral ulcerations six years prior, which waxed and waned. Recently, she had developed genital lesions; hence, the rheumatologist established the diagnosis of Behcet’s disease. Lately, she developed skin lesions that healed before her first visit to our clinic. On her first visit, she was taking prednisolone 5 mg once daily, azathioprine (AZA) 150 mg once daily, and colchicine 0.5 mg once daily. Adalimumab was administered for 7 months without substantial benefit and was discontinued 8 months before the visit. Clinical examination revealed erosions and crusting on both the upper and lower lips (Fig. 1b). Intraorally, ulceration was seen on the buccal mucosa bilaterally, floor of the mouth, and left lateral border of the tongue. Our tentative diagnoses were PV and EM. Two incisional biopsies were obtained and examined by routine H&E and DIF, which demonstrated similar findings as in Case 1 (Fig. 2b). Therefore, the diagnosis of PV was confirmed. The patient was started on prednisolone 1 mg/kg/d (50 mg) and advised to continue azathioprine 150 mg once daily. Approximately 6 weeks after the initiation of prednisolone treatment, the oral lesion went into the remission phase, and prednisolone was tapered gradually (10 mg every 10 days). During the follow-up period, the patient had several exacerbations in which the systemic steroid dose was adjusted based on the clinical findings and the response to therapy. Furthermore, topical steroid mouthwash (dexamethasone 0.5 mg/5 ml) and nystatin oral suspension as mouthwash 100.000 IU/ml were used frequently.

A 33-year-old female patient of Syrian descent presented to the Clinic of Oral Medicine, Public Dental Health, Gothenburg, Sweden, Region Västra Götaland of Sweden. She complained of painful ulcers in the oral cavity and lips that started seven months prior, accompanied by a feeling of burning sensation, itching, and pain. The patient also complained of dysphagia, which prompted her to seek out an ENT physician. Upon examination by ENT, ulcers were observed at the epiglottis. The patient had no significant medical history but was admitted for investigation of suspected Behçet’s disease. Clinical examination revealed ulcerations on the ventral surface of the tongue and lateral borders of the tongue, palate, and throat. The lip lesions presented as erosions coated with crusting (Fig. 1c). Our tentative diagnosis was EM with secondary infected ulcers and PV. A sample for microbiology examination was taken from the outer surface of the lower lip. This sample demonstrated the presence of Staphylococcus aureus. For the treatment of the lip lesions, topical retapamulin 10 mg/g for 5 days and topical hydrogen peroxide 1% for one week, both twice daily, were prescribed. A 4-mm punch biopsy was taken from the perilesional area of the upper labial mucosa. Routine H & E examinations revealed findings similar to those in Case 1, suggesting PV (Fig. 2c). Subsequently, another 4-mm punch biopsy was taken from the lower labial mucosa for DIF examination, which demonstrated intercellular deposition of IgG and C3 in a net-like pattern. Indirect IF revealed the presence of antibodies against desmoglein 3. Blood samples were negative for antibodies against envoplakin, thus ruling out paraneoplastic pemphigus. Accordingly, the diagnosis of PV was confirmed, and the patient was then referred to the dermatology department for management. Her initial treatment regimen included prednisolone 0.5 mg/kg (30 mg per day), omeprazole 20 mg and Calcichew-D forte 500 mg as osteoporosis prophylaxis per day. The patient complained of discomfort in the eyes and genital mucosa, but no manifestation of PV was seen in these locations. Approximately two months after the initiation of steroid therapy, the patient achieved remission of her oral lesions. After remission, the prednisolone dose was decreased by 5 mg per week but with some plateau effect. One year after the initiation of prednisolone treatment, the dose was 5 mg per day. The patient continued her treatment with tapering steroids, and after seven years, the patient was taking 2.5 mg prednisolone every other day in combination with Calcichew-D 500 mg daily. The Dexa scan showed no signs of osteoporosis. Topical treatment with clobetasol propionate 0.025% oral gel in combination with local antifungal medication Nystimex oral suspension 10.0000 IU/ml was prescribed for use when exacerbation occurred. The patient did not have any skin lesions during the seven-year follow-up period.

A 64-year-old Yemeni female presented to the Oral Medicine Clinic of the Faculty of Dentistry at King Abdulaziz University, Jeddah, Saudi Arabia. Her chief complaint was ulceration of the lip, tongue and buccal mucosa. Her medical history was significant for hypertension, hyperlipidemia, and hypothyroidism. She was taking irbesartan 150 mg/12.5 mg, atenolol 50 mg, rosuvastatin 10 mg, levothyroxine 150 mg, Calcos Vit. D3 500 mg/400 IU, pregabalin, Jus aspirin 81 mg, acyclovir 200 mg/5 ml and topical hyaluronic acid. Clinical examination revealed erosions and crusting of the lower lip. Intraorally, ulceration was seen on the palatal mucosa, lateral borders of the tongue and lower anterior attached gingiva labially (Fig. 1d). The provisional diagnosis was PV. An incisional biopsy was taken from the palate for routine H&E examination, which revealed findings comparable to those of Case 1 (Fig. 2d). Thus, the diagnosis of PV was confirmed. For treatment, prednisolone syrup 15 mg/5 ml as a mouthwash three times daily and prednisolone 1 mg/kg/d (60 mg) were initiated, followed by azathioprine 100 mg once daily. Follow-up was performed every 2 weeks initially for 2 months and then every 3 months. The patient’s condition was controlled after 3 months, and systemic prednisolone was tapered over 6 months. The patient remained on azathioprine for 18 months, after which she developed fatigue and requested discontinuation of the medication. The patient was subsequently controlled with a topical steroid rinse. The last follow-up was performed 5 years after the initial diagnosis.

A 37-year-old Saudi male patient presented to the Oral Medicine Clinic at the Faculty of Dentistry at King Abdulaziz University, Jeddah, Saudi Arabia. He complained of pain while eating and drinking, in addition to a limited ability to open his mouth for the last two months. The patient had no significant medical history. He was a smoker who had used approximately 10 cigarettes per day for the last 12 years. Upon clinical examination, ulcerations were observed on the upper and lower lips with crusting. Erosions were observed bilaterally on the ventral surface of the tongue, floor of the mouth and buccal mucosa (Fig. 1e). An incisional biopsy was taken from the lower lip for routine H&E examination, which was also suggestive of PV, as in the previous cases (Fig. 2e). Hence, a diagnosis of PV was established. Prednisolone 45 mg/day was initiated and continued for two weeks, and the dose was subsequently tapered over 3 months. In addition to systemic treatment, topical treatment was added using prednisolone syrup 15 mg/5 ml as a mouthwash thrice daily for 3 months. Two months later, he presented with a relapse of intraoral lesions in which azathioprine 50 mg, once daily, was added to the preexisting steroid mouthwash. Follow-up was performed every 2 weeks for 2 months and then every 3 months. The patient was then lost to follow-up.

A 57-year-old Saudi female patient presented to the Oral Medicine Clinic at the Faculty of Dentistry at King Abdulaziz University, Jeddah, Saudi Arabia. The patient’s main complaints were pain and labial ulcerations. She had hypothyroidism for which she was taking levothyroxine. Clinical examination revealed widespread ulcerations and erosions intraorally. The upper and lower lips exhibited erosions, ulcerations and crusting (Fig. 1f). Extraorally, skin lesions were observed around the armpit. The patient also had genital lesions. An incisional biopsy was taken from the lower labial mucosa for routine H&E examination, which demonstrated findings consistent with PV (Fig. 2f). The patient started treatment with prednisolone 40 mg once daily as well as topical treatment with prednisolone syrup 15 mg/5 ml as a mouthwash thrice daily for 3 months. During multiple follow-up visits, the patient relapsed once steroids were tapered, and she was referred to a dermatologist at a tertiary care center for rituximab therapy. She was treated and followed up there.