By Gary M. White, MD
Pemphigus vulgaris (PV) is an autoimmune blistering disorder caused by circulating antibodies to epidermal adhesion molecules, primarily desmoglein 3.
Widespread, flaccid bulla and crusted erosions in a middle-aged patient is classic. Oral erosions are characteristic and the patient may present with only oral ulcerations. The esophagus may be involved and sloughing of its entire surface has been reported. Associated malignancies have included thymoma, lymphoma, Kaposi's sarcoma, lung, and breast cancer. DIF shows intercellular IgG and/or C3. IIF is usually positive and its titer may correlate with disease activity. Nikolsky's sign is present. Untreated PV has a high mortality. With treatment, current mortality averages about 6%. Rarely, nail dystrophy or paronychia may occur. There is an increased susceptibility to the development of autoimmune diseases in the family members of patients with PV. Nikolsky's sign is positive: splitting of the epidermal of normal skin with shear force.
Genital involvement is not uncommon. In one study of 34 women with PV [October 2015;73;655–659], vulvar involvement was observed in 44.1% and was significantly associated with nasal mucosa involvement.
Diagnosis can be made with either direct or indirect immunofluorescence using serum to detect antibodies to desmoglien 1 and/or 3.
Drug-induced PV is well recognized. Long-term therapy with interferon alpha seems to induce pemphigus antibodies with or without clinical pemphigus [Dermatology 1996;192;50].
The growing consensus is that rituximab should be first-line therapy, but it has a delayed onset of action. Thus, rituximab should be given as soon as possible but systemic steroids (and other agents, e.g., azathioprine) are needed early to control the disease until the rituximab effects are manifested. Combining rituximab with clobetasol topically as first-line therapy has been recommended as noted below.
One study of 11 patients with recalcitrant disease (including patients who failed IVIG alone) treat with both IVIG and rituximab achieved complete control in all 11 [N Engl J Med 2006; 355:1772-1779]. The regimen used was two cycles of rituximab (375 mg per square meter of body-surface area) once weekly for 3 weeks and intravenous immune globulin (2 g per kilogram of body weight) in the fourth week. This induction therapy was followed by a monthly infusion of rituximab and intravenous immune globulin for 4 consecutive months. This achieved complete response in 9/11. The other 2 required additional therapy which ultimately controlled the disease.
A comparative study of rituximab 2 x 500 mg vs 2 x 1000 mg suggests improved outcomes in patients receiving the higher dose [British Journal of Dermatology 170:6:1341–1349, June 2014]. A report of 5 patients combined rituximab 1000 mg day 1 and 15 (one patient 375 weekly) with topical clobetasol 5-20 grams/day with good results [JAMA Derm 2015;151;200]. Their mean time to healing was 15 weeks. Patient may receive a very short course or therapy may last years (at lower frequency).In another study using this regimen (JAMA Dermatol. Published online February 05, 2014), median time to relapse after the first treatment cycle was 15 months.
Desmoglein levels drop with rituximab therapy. One course of rituximab as outlined above and treatment of relapses is recommended. Prophylactic infusion of rituximab in one study did not help.
Intralesional rituximab was very effective for 3 patients (2 injections on days 1 and 15 of intralesional rituximab, 5 mg/cm2) in one report [JAMA
IVIG is usually combined with rituximab in the treatment of pemphigus. However it does show benefit as monotherapy as demonstrated in this DBPCT for PV (and Pemphigus foliaceous) [JAAD 2009;60:595]. Typical doses of IVIG are 400 mg/kg/day for 5 days followed by long- or short-term single doses of 400 mg/kg/day every 6 weeks for 6 months to 1 year. Improvement usually occurs within 2–3 weeks of the first IVIg infusion.
Veltuzumab, a humanized anti-CD20 antibody given subcutaneously twice, two weeks apart, using a compassionate use protocol, completely cleared one patient's PV for 2 years [JAMA Derm 2014;150;1331].
Prednisone, e.g., 1 mg/kg or higher, is usually needed early on to control the disease. The dose is tapered as the benefits of rituximab "kick in."
E.g., 2 mg/kg/day
Immunoadsorption or the depleting of autoantibodies is an effective and relatively safe treatment of pemphigus and may be combined with other therapies [BJD 2003:148:1222].
Pemphigus is rare in children. Rituximab appears to be a good therapeutic option [JAAD 2014;71;669]. Other options include systemic steroids, azathioprine, dapsone, mycophenolate mofetil, cyclophosphamide, and IVIG.
PV of the nail.
This great case shows how pemphigus may only affect the penis. Indian J Dermatol Venereol Leprol 2015;81:298-9