Pemphigus foliaceus

Anti-DSG1 (&3) autoimmune disease

Most common in middle age, but it has also been described from 18 months to 70 years of age.

• Classical variant
• Pemphigus erythematosus Senear Usher

Autoimmune reaction with antibodies against DSG1 (&3)

Frequently not perceptible as bullae, erythematous, partly erosive, finely scaling areas focussed on the seborrhoeic zones. May look similar to eczema. May itch and burn. Typical onset is after emotional stress (33% of cases), otherwise risk factors sunlight, heat.

Biopsy with direct immunofluorescence

Anti-desmoglein 1 & 3

Seborrhoeic zones, but can affect the whole body. Does not go on the mucous membranes.

Burning and itching blisters developed, mechanical? Trigger stress? Muscle weakness?

Superficial intraepidermal bullae. There is nothing in the cavities, or fibrin, or even neutrophils. Dyskeratotic cells in the str. granulosum are suggestive of pemphigus foliaceus. Early on, eosinophilic spongiosis may also occur, in which case attention should be paid to the differential diagnosis of bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis.

Direct immunofluorescence positive in almost 100%, intercellular immunoglobulins and complement in the epidermis.

Impetiginisation.

None possible.

Relatively good, can give punctual recurrences.

• Abasq C, Mouquet H, Gilbert D, et al. ELISA testing of anti-desmoglein 1 and 3 antibodies in the management of pemphigus. Arch Dermatol 2009; 145:529.
• Aberer W, Wolff-Schreiner EC, Stingl G, Wolff K. Azathioprine in the treatment of pemphigus vulgaris. A long-term follow-up. J Am Acad Dermatol 1987; 16:527.
• Ahmed AR, Nguyen T, Kaveri S, Spigelman ZS. 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. Int Immunopharmacol 2016; 34:25.
• Almugairen N, Hospital V, Bedane C, et al. Assessment of the rate of long-term complete remission off therapy in patients with pemphigus treated with different regimens including medium- and high-dose corticosteroids. J Am Acad Dermatol 2013; 69:583.
• Alpsoy E, Yilmaz E, Basaran E, et al. Is the combination of tetracycline and nicotinamide therapy alone effective in pemphigus? Arch Dermatol 1995; 131:1339.
• Amagai M, Komai A, Hashimoto T, et al. Usefulness of enzyme-linked immunosorbent assay using recombinant desmogleins 1 and 3 for serodiagnosis of pemphigus. Br J Dermatol 1999; 140:351.
• Anstey AV, Wakelin S, Reynolds NJ, British Association of Dermatologists Therapy, Guidelines and Audit Subcommittee. Guidelines for prescribing azathioprine in dermatology. Br J Dermatol 2004; 151:1123.
• Atzmony L, Hodak E, Leshem YA, et al. The role of adjuvant therapy in pemphigus: A systematic review and meta-analysis. J Am Acad Dermatol 2015; 73:264.
• Basset N, Guillot B, Michel B, et al. Dapsone as initial treatment in superficial pemphigus. Report of nine cases. Arch Dermatol 1987; 123:783.
• Baum S, Debby A, Gilboa S, et al. Efficacy of Dapsone in the Treatment of Pemphigus Vulgaris: A Single-Center Case Study. Dermatology 2016; 232:578.
• Baum S, Greenberger S, Samuelov L, et al. Methotrexate is an effective and safe adjuvant therapy for pemphigus vulgaris. Eur J Dermatol 2012; 22:83.
• Beissert S, Mimouni D, Kanwar AJ, et al. Treating pemphigus vulgaris with prednisone and mycophenolate mofetil: a multicenter, randomized, placebo-controlled trial. J Invest Dermatol 2010; 130:2041.
• Beissert S, Werfel T, Frieling U, et al. A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of pemphigus. Arch Dermatol 2006; 142:1447.
• Burton JL, Greaves MW, Marks J, Dawber RP. Azathioprine in pemphigus vulgaris. Br Med J 1970; 3:84.
• Bystryn JC, Rudolph JL. Pemphigus. Lancet 2005; 366:61.
• Bystryn JC, Steinman NM. The adjuvant therapy of pemphigus. An update. Arch Dermatol 1996; 132:203.
• Caldarola G, Kneisel A, Hertl M, Feliciani C. Herpes simplex virus infection in pemphigus vulgaris: clinical and immunological considerations. Eur J Dermatol 2008; 18:440.
• Carson PJ, Hameed A, Ahmed AR. Influence of treatment on the clinical course of pemphigus vulgaris. J Am Acad Dermatol 1996; 34:645.
• Chaffins ML, Collison D, Fivenson DP. Treatment of pemphigus and linear IgA dermatosis with nicotinamide and tetracycline: a review of 13 cases. J Am Acad Dermatol 1993; 28:998.
• Chams-Davatchi C, Esmaili N, Daneshpazhooh M, et al. Randomized controlled open-label trial of four treatment regimens for pemphigus vulgaris. J Am Acad Dermatol 2007; 57:622.
• Chams-Davatchi C, Mortazavizadeh A, Daneshpazhooh M, et al. Randomized double blind trial of prednisolone and azathioprine, vs. prednisolone and placebo, in the treatment of pemphigus vulgaris. J Eur Acad Dermatol Venereol 2013; 27:1285.
• Chams-Davatchi C, Valikhani M, Daneshpazhooh M, et al. Pemphigus: analysis of 1209 cases. Int J Dermatol 2005; 44:470.
• Chatterjee M, Meru S, Vasudevan B, et al. Pemphigus foliaceus masquerading as IgA pemphigus and responding to dapsone. Indian J Dermatol 2012; 57:495.
• Cheng SW, Kobayashi M, Kinoshita-Kuroda K, et al. Monitoring disease activity in pemphigus with enzyme-linked immunosorbent assay using recombinant desmogleins 1 and 3. Br J Dermatol 2002; 147:261.
• Cho YT, Lee FY, Chu CY, Wang LF. First-line combination therapy with rituximab and corticosteroids is effective and safe for pemphigus. Acta Derm Venereol 2014; 94:472.
• Chrysomallis F, Ioannides D, Teknetzis A, et al. Treatment of oral pemphigus vulgaris. Int J Dermatol 1994; 33:803.
• Cirillo N, Cozzani E, Carrozzo M, Grando SA. Urban legends: pemphigus vulgaris. Oral Dis 2012; 18:442.
• Colliou N, Picard D, Caillot F, et al. Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response. Sci Transl Med 2013; 5:175ra30.
• Craythorne EE, Mufti G, DuVivier AW. Rituximab used as a first-line single agent in the treatment of pemphigus vulgaris. J Am Acad Dermatol 2011; 65:1064.
• De Simone C, Caldarola G, Perino F, et al. Enteric-coated mycophenolate sodium as a steroid-sparing agent in pemphigus treatment: a retrospective study. Dermatol Ther 2012; 25:219.
• Enk AH, Knop J. Mycophenolate is effective in the treatment of pemphigus vulgaris. Arch Dermatol 1999; 135:54.
• Femiano F, Gombos F, Scully C. Pemphigus vulgaris with oral involvement: evaluation of two different systemic corticosteroid therapeutic protocols. J Eur Acad Dermatol Venereol 2002; 16:353.
• Gniadecki R, Bygum A, Clemmensen O, et al. IgA pemphigus: the first two Scandinavian cases. Acta Derm Venereol 2002; 82:441.
• Grando SA. Pemphigus autoimmunity: hypotheses and realities. Autoimmunity 2012; 45:7.
• Gürcan HM, Ahmed AR. Analysis of current data on the use of methotrexate in the treatment of pemphigus and pemphigoid. Br J Dermatol 2009; 161:723.
• Gürcan HM, Ahmed AR. Efficacy of dapsone in the treatment of pemphigus and pemphigoid: analysis of current data. Am J Clin Dermatol 2009; 10:383.
• Harman KE, Albert S, Black MM, British Association of Dermatologists. Guidelines for the management of pemphigus vulgaris. Br J Dermatol 2003; 149:926.
• Harman KE, Brown D, Exton LS, et al. British Association of Dermatologists' guidelines for the management of pemphigus vulgaris 2017. Br J Dermatol 2017; 177:1170.
• Hertl M, Jedlickova H, Karpati S, et al. Pemphigus. S2 Guideline for diagnosis and treatment--guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV). J Eur Acad Dermatol Venereol 2015; 29:405.
• Hertl M. Pemphigus vulgaris. CME Dermatol 2009; 4:94.
• Hirata Y, Abe R, Kikuchi K, et al. Intraepidermal neutrophilic IgA pemphigus successfully treated with dapsone. Eur J Dermatol 2012; 22:282.
• Ingen-Housz-Oro S, Valeyrie-Allanore L, Cosnes A, et al. First-line treatment of pemphigus vulgaris with a combination of rituximab and high-potency topical corticosteroids. JAMA Dermatol 2015; 151:200.
• Ioannides D, Apalla Z, Lazaridou E, Rigopoulos D. Evaluation of mycophenolate mofetil as a steroid-sparing agent in pemphigus: a randomized, prospective study. J Eur Acad Dermatol Venereol 2012; 26:855.
• Ioannides D, Chrysomallis F, Bystryn JC. Ineffectiveness of cyclosporine as an adjuvant to corticosteroids in the treatment of pemphigus. Arch Dermatol 2000; 136:868.
• Ishii K, Amagai M, Hall RP, et al. Characterization of autoantibodies in pemphigus using antigen-specific enzyme-linked immunosorbent assays with baculovirus-expressed recombinant desmogleins. J Immunol 1997; 159:2010.
• Jackson AP, Hall AG, McLelland J. Thiopurine methyltransferase levels should be measured before commencing patients on azathioprine. Br J Dermatol 1997; 136:133.
• Joly P, Maho-Vaillant M, Prost-Squarcioni C, et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet 2017; 389:2031.
• Kasperkiewicz M, Schmidt E, Zillikens D. Current therapy of the pemphigus group. Clin Dermatol 2012; 30:84.
• Kneisel A, Hertl M. Autoimmune bullous skin diseases. Part 2: diagnosis and therapy. J Dtsch Dermatol Ges 2011; 9:927.
• Leshem YA, Gdalevich M, Ziv M, et al. Opportunistic infections in patients with pemphigus. J Am Acad Dermatol 2014; 71:284.
• Lever WF. Pemphigus. Medicine (Baltimore) 1953; 32:1.
• Lunardon L, Tsai KJ, Propert KJ, et al. Adjuvant rituximab therapy of pemphigus: a single-center experience with 31 patients. Arch Dermatol 2012; 148:1031.
• Martin LK, Werth V, Villanueva E, et al. Interventions for pemphigus vulgaris and pemphigus foliaceus. Cochrane Database Syst Rev 2009; :CD006263.
• Martin LK, Werth VP, Villaneuva EV, Murrell DF. A systematic review of randomized controlled trials for pemphigus vulgaris and pemphigus foliaceus. J Am Acad Dermatol 2011; 64:903.
• McCarty M, Fivenson D. Two decades of using the combination of tetracycline derivatives and niacinamide as steroid-sparing agents in the management of pemphigus: defining a niche for these low toxicity agents. J Am Acad Dermatol 2014; 71:475.
• Meggitt SJ, Anstey AV, Mohd Mustapa MF, et al. British Association of Dermatologists' guidelines for the safe and effective prescribing of azathioprine 2011. Br J Dermatol 2011; 165:711.
• Mentink LF, Mackenzie MW, Tóth GG, et al. Randomized controlled trial of adjuvant oral dexamethasone pulse therapy in pemphigus vulgaris: PEMPULS trial. Arch Dermatol 2006; 142:570.
• Mimouni D, Anhalt GJ, Cummins DL, et al. Treatment of pemphigus vulgaris and pemphigus foliaceus with mycophenolate mofetil. Arch Dermatol 2003; 139:739.
• Mimouni D, Nousari CH, Cummins DL, et al. Differences and similarities among expert opinions on the diagnosis and treatment of pemphigus vulgaris. J Am Acad Dermatol 2003; 49:1059.
• Mobini N, Padilla T Jr, Ahmed AR. Long-term remission in selected patients with pemphigus vulgaris treated with cyclosporine. J Am Acad Dermatol 1997; 36:264.
• Mourellou O, Chaidemenos GC, Koussidou T, Kapetis E. The treatment of pemphigus vulgaris. Experience with 48 patients seen over an 11-year period. Br J Dermatol 1995; 133:83.
• Murrell DF, Dick S, Ahmed AR, et al. Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus. J Am Acad Dermatol 2008; 58:1043.
• Nagel A, Lang A, Engel D, et al. Clinical activity of pemphigus vulgaris relates to IgE autoantibodies against desmoglein 3. Clin Immunol 2010; 134:320.
• Powell AM, Albert S, Al Fares S, et al. An evaluation of the usefulness of mycophenolate mofetil in pemphigus. Br J Dermatol 2003; 149:138.
• Ratnam KV, Phay KL, Tan CK. Pemphigus therapy with oral prednisolone regimens. A 5-year study. Int J Dermatol 1990; 29:363.
• Smith TJ, Bystryn JC. Methotrexate as an adjuvant treatment for pemphigus vulgaris. Arch Dermatol 1999; 135:1275.
• Sollinger HW, Sundberg AK, Leverson G, et al. Mycophenolate mofetil versus enteric-coated mycophenolate sodium: a large, single-center comparison of dose adjustments and outcomes in kidney transplant recipients. Transplantation 2010; 89:446.
• Strowd LC, Taylor SL, Jorizzo JL, Namazi MR. Therapeutic ladder for pemphigus vulgaris: emphasis on achieving complete remission. J Am Acad Dermatol 2011; 64:490.
• Suzuki M, Karube S, Kobori Y, et al. IgA pemphigus occurring in a 1-month-old infant. J Am Acad Dermatol 2003; 48:S22.
• Tran KD, Wolverton JE, Soter NA. Methotrexate in the treatment of pemphigus vulgaris: experience in 23 patients. Br J Dermatol 2013; 169:916.
• Vardy DA, Cohen AD. Cyclosporine therapy should be considered for maintenance of remission in patients with pemphigus. Arch Dermatol 2001; 137:505.
• von Köckritz A, Ständer S, Zeidler C, et al. Successful monotherapy of pemphigus vegetans with minocycline and nicotinamide. J Eur Acad Dermatol Venereol 2017; 31:85.
• Werth VP, Fivenson D, Pandya AG, et al. Multicenter randomized, double-blind, placebo-controlled, clinical trial of dapsone as a glucocorticoid-sparing agent in maintenance-phase pemphigus vulgaris. Arch Dermatol 2008; 144:25.
• Werth VP. Treatment of pemphigus vulgaris with brief, high-dose intravenous glucocorticoids. Arch Dermatol 1996; 132:1435.