OBJECTIVES: The aim of this study is to determine the effect of cannabinoid receptor (CB) 2 inhibitor on desmoglein 3 (DSG3) expression in HaCaT cells co-cultured with pemphigus serum. METHODS: Immunohistochemical staining was used to compare CB expression in pemphigus patients and normal individuals. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the concentration of CB2 in the serum of pemphigus patients and normal individuals. A correlation analysis was performed to examine the relationship between the serum CB2 and DSG of pemphigus patients. The CCK-8 assay was used to evaluate the inhibitory effect of AM630 on HaCaT cells, and the half-maximal inhibitory concentration (IC₅₀) value was utilized to determine the experimental concentration. Serum from normal individuals (negative control group) and pemphigus patients (pemphigus group) was co-cultured with HaCaT cells at a 1∶1 ratio. HaCaT cells cultured in complete medium were used as the control group. HaCaT cells in the pemphigus group treated with AM630 were employed as the AM630 group. Real-time polymerase chain reaction (PCR) and Western blot were conducted to assess the expression levels of CB2, DSG3, and β-catenin. Cell dissociation experiments were conducted to evaluate the effect of AM630 on the adhesion of HaCaT cells. RESULTS: Immunohistochemistry revealed significant differences in CB2 expression between pemphigus and normal mucosa (P<0.000 1), but no difference was found in CB1 expression. ELISA analysis revealed a statistically significant difference in the expression levels of CB2 in the serum between normal individuals and pemphigus patients (P<0.001). The expression of CB2 in the serum of pemphigus patients exhibited a significant positive correlation with that of DSG3 (r=0.831, P=0.003). The CCK-8 assay indicated that the IC₅₀ of AM630 on HaCaT cells was 0.55 μmol/L. Real-time PCR and Western blot showed that the expression levels of CB2 and DSG3 increased in the pemphigus group, while the expression level of β-catenin decreased compared with that in the AM630 groups (P<0.05). CONCLUSIONS CB2 is highly expressed in oral mucosal pemphigus. AM630 inhibits overexpression of CB2 and DSG3 and underexpression of β-catenin levels, which can provide new therapeutic targets for pemphigus.
Humans ; Pemphigus/pathology* ; Receptor, Cannabinoid, CB2/metabolism* ; Desmoglein 3/metabolism* ; Acantholysis/metabolism* ; Mouth Mucosa/pathology* ; HaCaT Cells ; Coculture Techniques ; beta Catenin/metabolism*

Hailey-Hailey Disease (HHD) is a rare, chronic skin condition characterized by relapsing episodes and spontaneous remissions, significantly affecting patients’ quality of life, especially in severe cases. Due to its rarity, there are no established evidence-based treatment guidelines or extensive clinical trials. This case report highlights the rapid improvement of HHD in a 55-year-old Filipino woman treated with a combination of 5-fluorouracil and excimer phototherapy, suggesting that this treatment approach may be an effective alternative for managing the disease.

Pemphigus is a rare, chronic, life-threatening autoimmune blistering disease characterized by blisters and erosions of the skin and mucous membranes. Rituximab has been approved as a first-line treatment for moderate to severe pemphigus vulgaris. Despite of its efficacy in achieving remission, Rituximab can also lead to serious complications such as Hepatitis B reactivation.

We present a case of a 42-year-old Filipino male with severe pemphigus vulgaris on chronic immunosuppressive therapy. He had a 10-month history of multiple bullae and crusted erosions associated with pruritus and burning pain on the mouth resulting to odynophagia and dysphagia. He is a known case of chronic Hepatitis B with unrecalled vaccination status. On physical examination, Nikolsky and Asboe-Hansen signs were positive. Histopathology show intraepidermal split and row of suprabasal keratinocytes pattern. ELISA showed very high levels (>200 RU/ml) for both anti-desmoglein 1 & 3. DIF was positive for IgG & C3. Prior to Rituximab administration, Tenofovir 300 mg/tab/day was started as pre-emptive therapy. To lessen the dependence on systemic corticosteroids, two infusions of Rituximab 1g 2 weeks apart were then given. Notable improvement was seen, evidenced by absence of new bullae, reduction of affected BSA, from 19% to 5.3% and decreased PDAI (78 to 1) and ABSIS (46.5 to 2.75) four months after treatment. Maintained remission and undetectable Hepatitis B viral load 4 months following the last dose of Rituximab were noted, indicating a positive treatment response to both Rituximab and Tenofovir.

Rituximab represents a viable treatment option even for patients with chronic Hepatitis B. Pre-emptive therapy may be done prior to infusion to prevent hepatitis reactivation. Clinical evidence supports the efficacy and safety of Rituximab in this case where preventive measures are taken.

BACKGROUND

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are rare, chronic autoimmune blistering diseases primarily treated with systemic glucocorticoids. Long-term use of glucocorticoids can result in significant adverse effects, leading to the exploration of steroid-sparing adjuvants. This meta-analysis aimed to evaluate the efficacy and safety of glucocorticoids alone versus in combination with adjuvants for treating PV and PF.

The main objective of this study was to compare the efficacy and safety of oral glucocorticoids alone versus with steroid-sparing adjuvants in treatment of PV and PF.

This research was a systematic review and quantitative meta-analysis of randomized controlled trials (RCTs) that compared systemic glucocorticoids with or without steroid-sparing adjuvants in treating PV and PF. A total of 20 RCTs were included after meeting the inclusion criteria, comprising 1169 patients diagnosed with PV or PF. Primary outcomes were remission rates, while secondary outcomes included relapse rates, disease control, and the occurrence of adverse events.

Studies involving rituximab and cyclophosphamide demonstrated significantly higher remission rates compared to other adjuvants or glucocorticoid monotherapy. Adverse events were common, particularly with high-dose glucocorticoids.

The meta-analysis found that rituximab and cyclophosphamide were superior steroid-sparing adjuvants in the treatment of PV and PF. Other adjuvants, such as azathioprine and mycophenolate mofetil, also showed efficacy but had a higher incidence of adverse events. Further studies were needed to optimize treatment protocols and reduce long-term complications.

Here, we present a 40-year-old female with multiple pruritic occasionally painful vesicles, papules, and plaques in a circinate pattern on seborrheic areas, progressing to erosions and scales. Clinical findings led to the diagnosis of pemphigus foliaceus (PF). Initial treatment with prednisone and clobetasol ointment, however, did not fully suppress blister formation and healing of erosions. Skin punch biopsy revealed a subcorneal split and intracorneal neutrophilic infiltrates, while enzymelinked immunoassay (ELISA) revealed elevated anti-desmoglein 1 (Dsgl), consistent with PF. Doxycycline was then added to the previous regimen, resulting in remission. We discuss the role of doxycycline as a cost-effective adjunctive treatment in patients with refractory PF.
Pemphigus ; Clobetasol ; Enzyme-Linked Immunosorbent Assay

Pemphigus foliaceus (PF) is a chronic, benign, acquired autoimmune blistering disease characterized by fragile, superficial blisters and bullae.1 2 3 Patients commonly report blister formation on the skin, followed by localized lesions that typically begin on the trunk, face, or scalp.2 PF is a rare disease with a very low worldwide incidence and prevalence. However, it has a high incidence in endemic areas located in North Africa, Brazil, Colombia, and Peru.2 3 4 The disease affects both sexes equally, with symptoms typically appearing between the ages of 50 and 60 years.2 4 The universal type of PF that occurs sporadically is idiopathic, while the endemic type is linked exclusively to geographically-related environmental factors.
Pemphigus

Psoriasis is a systematic immune-mediated inflammatory disease where there is an increased cell turnover of the skin leading to scaling, drying, and erythema. The occurrence of pemphigus foliaceus, an autoimmune blistering disease (AIBD) characterized by flaccid bullae and erosions, is rare when concomitantly present with psoriasis. Treatment options for these diseases may overlap. We report a case of a 44-year-old female who presented with both psoriasis and pemphigus foliaceus successfully treated with methotrexate.
Pemphigus ; Methotrexate

Cheilitis ; Humans ; Pemphigus/diagnosis*

OBJECTIVE: Critically ill patients with solid tumors complicated with paraneoplastic pemphigus are usually treated in intensive care units (ICU) for perioperative management after surgical treatment. In this study, the clinical characteristics and predictors of long-term prognosis of these critically ill patients were analyzed. METHODS: the clinical and laboratory data of 63 patients with solid tumors complicated with paraneoplastic pemphigus admitted to ICU from 2005 to 2020 were retrospectively analyzed, and the survival status of the patients were followed up. RESULTS: Among the 63 patients, 79.4% had Castleman disease as the primary tumor, and 20.6% with other pathological types; 69.8% had severe-extensive skin lesions, and 30.2% had other skin lesions; the patients with bronchiolitis obliterans accounted for 44.4%, and 55.6% were not merged. Postoperative fungal infection occurred in 23.8% of the patients, and 76.2% without fungal infection. The median follow-up time was 95 months, and 25 patients died during the study period. The 1-year, 3-year and 5-year survival rates were 74.6% (95%CI 63.8%-85.4%), 67.4% (95%CI 55.6%-79.2%) and 55.1% (95%CI 47.9%-62.3%), respectively. The log-rank univariate analysis showed that the patients had age>40 years (P=0.042), preoperative weight loss>5 kg (P=0.002), preoperative albumin < 30 g/L (P < 0.001), paraneoplastic pemphigus complicated with bronchiolitis obliterans (P=0.002), and perioperative fungal infection (P < 0.001) had increased mortality. Cox univariate analysis showed that preoperative weight loss >5 kg (P=0.005), preoperative albumin < 30 g/L (P < 0.001), paraneoplastic pemphigus complicated with bronchiolitis obliterans (P=0.009), preoperative bacterial pulmonary infection (P=0.007), prolonged surgical time (P=0.048), postoperative oxygenation index (P=0.012) and low albumin (P=0.010) and hemoglobin concentration (P=0.035) in ICU, acute physiology and chronic health evaluation (APACHE Ⅱ) score (P=0.001); sequential organ failure assessment (SOFA) score (P=0.010), and postoperative fungal infection (P < 0.001) were risk factors for long-term survival. Cox regression model for multivariate analysis showed that preoperative weight loss > 5 kg (HR 4.44; 95%CI 1.47-13.38; P=0.008), and preoperative albumin < 30 g/L (HR 4.38; 95%CI 1.72-11.12; P=0.002), bronchiolitis obliterans (HR 2.69; 95%CI 1.12-6.50; P=0.027), and postoperative fungal infection (HR 4.85; 95%CI 2.01-11.72; P < 0.001) were independent risk factors for postoperative mortality. CONCLUSION The 5-year survival rate of critically ill patients undergoing surgery for paraneoplastic pemphigus combined with solid tumors is approximately 55.1%, with preoperative weight loss > 5 kg, albumin < 30 g/L, bronchiolitis obliterans and postoperative fungal infection were associated with an increased risk of near- and long-term postoperative mortality.
Adult ; Albumins/therapeutic use* ; Bronchiolitis Obliterans/pathology* ; Critical Illness ; Hemoglobins ; Humans ; Neoplasms/complications* ; Paraneoplastic Syndromes/pathology* ; Pemphigus/drug therapy* ; Retrospective Studies ; Weight Loss

Introduction: Pemphigus vulgaris is a life-threatening, autoimmune bullous disease caused by desmogleins (Dsg) 1 and 3 au- toantibodies. It is a rare disease with an incidence rate of 0.5 to 3.2 per 100,000 per year. It typically presents as painful, flaccid blisters and erosions on both the skin and mucous membranes. Case report: We present a 43-year-old male with painless penile erosions of 1-month duration. He was evaluated for sexually transmitted infections, but laboratory tests yielded negative results. Subsequently, vesicles and bullae on the back and hyper- keratotic lesions on the malar area appeared, leading to the differential diagnoses of bullous diseases. Skin biopsy was done revealing intraepidermal suprabasal blisters with acantholytic cells. Direct Immunofluorescence demonstrated positive inter- cellular deposits of IgG and C3. ELISA Dsg 1 and Dsg 3 were positive (ratio of 1.857 and 4.580, respectively). A final diagnosis of pem- phigus vulgaris (PV) was made. The patient has remained in remission after a 3-month course of prednisone and azathioprine. Conclusion This is a unique case of PV presenting with an unusual manifestation of painless penile erosions. There have been limited reports of PV with penile skin involvement and all cases presented with painful lesions. Because painless penile lesions as presenting feature is rare, the diagnosis may be easily missed. This case demonstrates that thorough dermatologic examination and early diagnosis despite atypical findings are crucial to provide timely and appropriate treatment as this determines the clinical outcome of the disease.
Pemphigus ; Desmogleins ; Azathioprine