First line treatment of pemphigus vulgaris with a novel protocol in patients with contraindications to systemic corticosteroids and immunosuppressive agents: Preliminary retrospective study with a seven year follow-up.

BACKGROUND: Conventional therapy for pemphigus vulgaris (PV) consists of high-dose systemic corticosteroids (CS) and immunosuppressive agents (ISA). This combination may be ineffective, cause serious adverse events or relapses in some patients. OBJECTIVE: To determine if the combination of intravenous immunoglobulin (IVIg) therapy and rituximab (RTX) can be used as first-line therapy in PV patients in whom systemic CS and ISA are contraindicated and evaluate its ability to produce long-term sustained remissions. METHOD: This a retrospective study of five male and five female patients (mean age 47.87 years). RTX was administered once weekly for eight consecutive weeks, followed by once monthly for four months (dose 375 mg/m(2)). Since CD20(+) B cells were undetectable, IVIg was infused until they reached normal levels (dose 2 g/kg/cycle). IVIg was then continued according to published protocol. RESULTS: Initial clinical response and complete disease resolution occurred in a mean of 3.2 weeks and 7.4 weeks, respectively. Mean duration of rituximab therapy was 6.09 months and 33.7 months for IVIg therapy. Mean duration of follow-up after the last dose of rituximab was 86.08 months, during which all patients remained in complete remission. Mean length of total follow-up was 103.99 months. No relapses, infections, or hospitalizations were reported. CONCLUSIONS: When systemic CS and ISA are contraindicated in PV patients, combination RTX and IVIg therapy can produce a prolonged, sustained remission without additional systemic therapy. This positive clinical outcome could be the consequence of pathogenic B cell depletion and restoration of immune regulation.

Autoimmune progesterone dermatitis: Update and insights.

UNLABELLED: Autoimmune progesterone dermatitis (APD) is rare autoimmune hypersensitivity reaction to the fluctuations of endogenous progesterone during a woman's menstrual cycle. It has a wide spectrum of clinical presentations including urticaria, eczema and vesiculobullous eruptions. The disease course depends on treatment modality. The pathogenic mechanisms of APD remain to be elucidated. OBJECTIVE: We aim to review the literature on APD and evaluate the different theories of pathogenesis and treatments for this condition. METHODS: A review of the English literature on APD was performed using PubMed, EMBASE and MEDLINE. RESULTS: 89 patients are included in this review. Initial symptom development in association with the menstrual cycle was reported in 65 (73%) patients. In some patients, it occurred shortly after hormone therapy (8.9%) or in relation to a pregnancy (14.6%). Associated factors were not defined in three patients (3.4%). Nearly 45% had a history of exposure to exogenous progesterone. Diagnosis of APD was usually confirmed with an intradermal progesterone sensitivity test. The goal of treatment was to suppress progesterone secretion through anovulation. Some cases were controlled with oral contraceptives or conjugated estrogen, while some patients had complete resolution post-hysterectomy. CONCLUSION: The wide spectrum of clinical presentations, histology, and response to therapy would suggest that there are multiple subsets in APD. The increase in the levels of progesterone may also influence the clinical profile and the corresponding immunological response. Further research on the pathogenesis of APD is required to provide a satisfactory treatment modality.

Positive clinical outcome with IVIg as monotherapy in recurrent pemphigoid gestationis.

Pemphigoid gestationis (PG) is an autoimmune blistering disease associated with pregnancy. It is characterized by the presence of autoantibodies against bullous pemphigoid antigens in the basement membrane zone. A 32 year old female developed PG in the first pregnancy and had a stillbirth. PG recurred during the second trimester of her second pregnancy. Systemic corticosteroid therapy was cause for concern since patient developed gestational diabetes. Patient was unwilling to use insulin. Intravenous immunoglobulin (IVIg) was used as a treatment of last resort. The dose was 2g/kg/cycle. It was given every two weeks antepartum and every three weeks for three months postpartum. PG improved within four weeks of IVIg therapy. Serum and tissue immunopathological studies were negative prior to delivery. A healthy neonate was born. No adverse events to IVIg were observed. No disease was observed ten months postpartum.

Pemphigus vulgaris localized to the tongue.

BACKGROUND: Pemphigus vulgaris is an autoimmune blistering disease that may initially present as localized lesions. It rarely remains localized throughout its clinical course. OBSERVATIONS: A 53-year-old woman with non-progressive pemphigus vulgaris localized to the tongue for 18 years is presented. Clinical examination showed erosions and ulcerations limited to the lateral margins of the tongue. Patient was treated with sublesional triamcinolone-acetonide injections as lesions recurred. Finally, triamcinolone- acetonide injections at three weeks intervals for three months induced a longterm sustained clinical remission for 18 months. The indirect immunofluorescence did not correlate with disease activity. Anti-desmoglein 3 antibodies (ELISA) remained elevated throughout the clinical course and during remission. CONCLUSIONS: This case highlights the recognition of localized pemphigus vulgaris and demonstrates the importance of local therapy and its potential to induce longterm remission. Similar report of additional cases may create a standard of care for non-progressive, localized pemphigus.

Relationship between radiation therapy and bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease. OBJECTIVE: To review the literature on radiation therapy (RT)-associated BP. METHODS: A review of the English language literature on patients who developed BP during and up to 10 years post RT was performed. RESULTS: 29 patients were reported. 25 (86.2%) were women, 84% of whom had received RT for breast cancer. Three patients were male (10.3%). Gender was not mentioned in 1 (3.4%). 72% developed BP post RT; 28% developed BP while undergoing RT. BP was initially localized to irradiated sites in 25 patients and to non-irradiated sites in 2 patients. Two patients presented with generalized disease. Disease control was reported in 12 patients, partial remission in 7 and complete remission in 5. CONCLUSION: The clinical profile, response to therapy and clinical outcome may indicate that RT-associated BP may be a specific subset of BP with a relatively benign course.

Mucous membranepemphigoid in two half-sisters. The potential roles of autoantibodies to ß4 integrin subunits and HLA-DQß1*0301.

BACKGROUND: Mucous membrane pemphigoid (MMP) is a subepithelial autoimmune mucocutaneous disease. It most frequently affects the oral mucosa, followed by ocular and nasal mucosa, nasopharyngeal, anogenital, skin, laryngeal and esophageal mucosa. MAIN OBSERVATION: Two half-sisters developed mucous membrane pemphigoid at approximately the same age. The older sister presented with primarily mucosal disease, while the younger had a more cutaneous disease. The histopathology demonstrated a subepithelial blister and direct immunofluorescence showed deposition of IgG and C3 at the basement membrane zone of perilesional tissues in both sisters. Antibodies to human ß4 integrin were present in the sera of both patients and correlated with disease activity. Both sisters carried the same HLADQß1* 0301 allele. CONCLUSIONS: This is the first case of mucous membrane pemphigoid occurring in two half-sisters. Perhaps, it is the low incidence of mucous membrane pemphigoid that may account for the lack of reports on familial cases of the disease.