Tools
Pemphigus Vegetans
Introduction
Pemphigus is a group of vesiculobullous autoimmune diseases. The most common type of pemphigus is pemphigus vulgaris, characterized by mucocutaneous bullae.[1] Among the many types of pemphigus, the rarest clinical variant is pemphigus vegetans. It distinguishes itself from pemphigus vulgaris by the formation of vegetative plaques in intertriginous areas and oral mucosa. Thought to be a subtype of pemphigus vulgaris, pemphigus vegetans represents 1-2% of all pemphigus [2]. It is often difficult to diagnose and clinically misleading due to the variable presentation and presence of verrucous vegetations.[3] There are two clinically recognized forms of pemphigus vegetans: the Hallopeau and Neumann. The Hallopeau type has an indolent course and characteristically demonstrates pustules that heal as vegetative plaques. The Neumann type is more severe and refractory to treatment, with vegetations that develop during an eruption of vesiculobullous lesions. The oral mucosa is usually involved.[4] The most common cause of pemphigus vegetans is autoantibodies against desmoglein 3 (DSG3) and desmoglein 1 (DSG1).[5] The mainstay of treatment for pemphigus vegetans is similar to that of pemphigus vulgaris, consisting of systemic corticosteroids and immunosuppressants.[2]
Etiology
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Etiology
Pemphigus vegetans results from autoantibodies against the transmembrane proteins that comprise desmosomes, which are responsible for keratinocyte cell-to-cell adhesion. Specifically, pemphigus vegetans is most commonly caused by autoantibodies against desmoglein 3 and often desmoglein 1.[5] Mucosal dominant disease is more frequently associated with desmoglein 3, and mucocutaneous disease is associated with autoantibodies against both desmoglein 3 and desmoglein 1. IgG and IgA antibodies against desmocollins are also present in patients with pemphigus vegetans.[6]
Epidemiology
The epidemiology of pemphigus vegetans has not been a topic of research. Reports are that it represents 1 to 2% of all pemphigus cases, and worldwide, the incidence of pemphigus vulgaris is approximately 0.7 per 100000. Given the limited cases, the epidemiology is thought to be similar to pemphigus vulgaris, which occurs more frequently in women, with a female-to-male ratio of between 1.3 and 2.3 to 1. Age at diagnosis is typically 50 to 70 years in the United States and European countries and 30 to 50 years in the remaining countries. Pemphigus vulgaris is reportedly more common among the Ashkenazi Jewish, Mediterranean, and Middle Eastern populations.[7][8]
Pathophysiology
The pathophysiology of pemphigus is characterized by IgG autoantibodies against the components of desmosomes that are responsible for keratinocyte adhesion, specifically desmoglein 3 and desmoglein 1. Autoantibody binding to desmogleins has been shown to cause blistering through several mechanisms- including steric hindrance, interruption of desmosome assembly and/or increased breakdown, and secondary activation of signal transduction events involving keratinocyte adhesion. Structural studies suggest steric hindrance from the molecular structure of the desmoglein-antibody complex creates the intraepidermal spaces that result in spongiosis and blister formation. These studies also show anti-desmoglein 3 antibodies present deep in the epidermis with concentrations of anti-desmoglein 1 antibodies in the upper epidermis.[9][5]
Autoantibody deposition against desmogleins within the epidermal space and on the outer surface of keratinocytes leads to acute inflammation and blister formation. In pemphigus vegetans, in addition to desmogleins 1 and 3, there are frequently antibodies to desmocollins 1 and 2. The addition of these antibodies has been suggested as an etiology for the difference in clinical appearance between pemphigus vulgaris and pemphigus vegetans and have been known to synergize with anti-desmoglein 3 antibodies to induce acantholysis.[10] It is still unknown how the characteristic vegetative lesions form following blister formation. Associated factors are thought to include semi-occlusion or maceration due to intertriginous location. Other theories suggest vegetative plaques form after serial bacterial or fungal infections as a protective response.
Genetics
There is a known component of genetic susceptibility to pemphigus. Studies have shown that certain human leukocyte antigen (HLA) alleles may be responsible for increased autoantibody formation against desmogleins. Mapping of the major histocompatibility complex region of chromosome 11 has shown an association between pemphigus vulgaris and HLA-DRB1 and HLA-DQB1, with the strongest association between HLA-DQB1*05:03.[11] In addition to increased genetic susceptibility, there is a hypothesis that B cells with VH1-46 heavy chain gene usage may be hypersensitive to desmoglein 3, increasing cellular damage.[12][13][14]
Histopathology
Classical histologic findings in pemphigus vegetans include hyperkeratosis, pseudoepitheliomatous hyperplasia, and papillomatosis, with acantholysis that creates a suprabasal cleft. The basal cells maintain their attachment to the basement membrane by intact hemidesmosomes, creating the characteristic appearance of “tombstones.” Follicular involvement is a frequent occurrence. Especially in the Hallopeau type, there is a strong eosinophilic response, with eosinophilic spongiosis, intraepidermal eosinophilic microabscesses, and dense eosinophilic dermal infiltrate. Neutrophils and lymphocytes usually accompany the eosinophilic response and are more likely to be the primary inflammatory component in the Neumann type. There may be papillary dermis edema to the heavy inflammatory infiltrate.[4]
History and Physical
The majority of patients initially present to their provider with stomatitis.[15] A few weeks to months after the mucosal blisters, cutaneous pustules and/or flaccid bullae form, typically affecting the trunk, arms, legs, and flexural areas. The Hallopeau subtype characteristically demonstrates initial pustular lesions and has a more indolent course. The Neumann subtype has characteristic large vesiculobullous erosive lesions and is more severe. The cutaneous lesions rupture and ulcerate, and verrucous, crusting vegetative plaques form over the erosions. These hyperkeratotic lesions characteristically present in the intertriginous areas- including the groin/inguinal folds, armpits, thighs, and flexural surfaces.[5] Less common areas affected include the scalp, soles of the feet, and skin graft sites. There are also reports of nasal, vaginal, and conjunctival involvement.[16][17] In the oral cavity, the hyperkeratotic plaques appear on the tongue in a cerebriform pattern.
Although most patients present with pertinent physical exam findings, it is important to take a detailed history- including a family and personal history of autoimmune disease and skin problems. Other relevant details include stressors, history of radiation, recent illness, changes in medications, or if there is pain associated with activities such as eating, swallowing, sexual activity, or if the symptoms flare with menstruation.[18]
Evaluation
The diagnosis of pemphigus vegetans is made based on clinical features, histologic examination, and identification of autoantibodies. There are several methods to evaluate and identify autoantibodies.[19]
Immunoblot or ELISA analysis of serum:
- Blood tests can identify patients with desmoglein 3 autoantibodies in their serum with a specificity and sensitivity of 98 to 100%, so nearly all patients with pemphigus will have detectable desmoglein 3 reactivity, and unaffected individuals will not.[10]
Direct Immunofluorescence (DIF):
- Similar to pemphigus vulgaris, the direct immunofluorescence findings in pemphigus vegetans show intercellular deposition of IgG and C3 within the intraepidermal space and on the surface of keratinocytes. IgG4 and IgG1 are the predominant types of IgG involved. This deposition creates a characteristic “fishnet” or “chicken wire” pattern.[9]
- For optimal DIF evaluation, a punch biopsy or deep shave from normal-appearing peri-lesional skin should be submitted in Michel’s solution (or fixative appropriate for DIF).
Serum immunoglobulins: IgG and IgA titers are often correlated with disease activity and can be used to follow therapeutic response.
Less commonly used methods of evaluation include:
- Indirect immunofluorescence (IIF) is a semi-quantitative method for identifying autoantibodies.
- Electron microscopy: Keratinocytes show a reduction of tonofilaments. Only rarely are there desmosomes identified. The basement membrane often appears damaged as a result of inflammatory infiltrates.[20]
Additional methods for evaluation:
- Nikolsky sign: Side pressure on the blister leads to blister extension. Often positive; however, this test is non-specific and seen in several blistering skin diseases.
- Tzanck test: Cutaneous cytology is useful to rule out pemphigus; however, the diagnosis should be by clinical exam, histopathology, and antibody identification. The reported sensitivity and specificity of a Tzanck smear is 85.0% and 83.33% for pemphigus.[21]
- Complete blood count with differential: May show peripheral eosinophilia.
Treatment / Management
Wound Care: Daily cleansing and dressing. Medicated gauzes and chemical cautery.[22]
Surgical options: Surgical excision of vegetative lesions.[22]
Treatment for Oral Involvement: Magic mouthwash comprised of liquid dexamethasone; 5 cc rinse, 2x per day, or clobetasol ointment.
- Class I steroids are applied twice daily
- Topical tacrolimus for facial involvement or if sensitive to chronic steroid therapy
- Minocycline/nicotinamide at onset and relapse has been used with success and avoids systemic steroids
Intralesional Therapy:
- Triamcinolone is injected directly into refractory vegetative lesions
Systemic Therapy: The gold standard for treatment is systemic corticosteroids. Corticosteroids are thought to upregulate desmoglein expression in keratinocytes, resulting in rapid therapeutic effect. Corticosteroids and immunosuppressants are the most effective in managing patients with pemphigus.[24]
- Prednisone: 0.5 to 2 mg/kg/day for 2 to 4 weeks.
- Azathioprine: 50 mg daily; upwards titrate to 2.5 mg/kg/day.
- Dapsone: 100 to 200mg daily. Ideal for mucosal involvement. It may combine with mycophenolate or azathioprine.[25]
- Mycophenolate mofetil: 30 to 40 mg/kg/day. Risk of side effects, lymphoma, and JC virus.
- Methotrexate: 15 mg/week. Safe and beneficial steroid-sparing agent.[26]
- Cyclophosphamide: Works well for oral mucosa but has an extensive side effect profile.
- First-line combination therapies:
- Corticosteroids plus one of the following agents: rituximab, mycophenolate mofetil, azathioprine, methotrexate, cyclophosphamide, or IVIG.
(B2)
If standard steroids and immunosuppressants are not sufficient, second-line treatments include:
- Rituximab, an anti-CD20 monoclonal antibody, with or without IVIG, dosed at 2 mg/kg over 3 to 5 days every 4 weeks. Rituximab has been shown to elucidate short-term remission in 95% to 100% of pemphigus patients and correlates with a decrease in anti-DSG3 titers.[10]
- Pulse Therapy: Intermittent high-dose IV corticosteroids and immunosuppressive agents to achieve faster results and minimize side effects of long-term steroid therapy.[27]
The recommendation is to maintain remission for 1 year and then slowly taper therapy over another year, tailored to the individual patient and their comorbidities.
Less common treatment options include plasmapheresis, immunoadsorption, and hematopoietic stem cell transplant.[24]
Emerging Therapies: The goal is to offer long-term therapy with fewer side effects and less systemic immunosuppression.
- B cell-activating factor (BAFF): B-cell-activating factor co-stimulates B-cell responses. Patients with B-cell-mediated autoimmune diseases often have increased BAFF, which makes it a novel therapeutic target.[28]
- Proliferation-inducing ligand (APRIL) inhibitors: Proliferation-inducing ligand is a key biomarker in the regulation of B-cells, humoral immunity, and pathogenicity of autoimmune disease. Inhibitors are a therapeutic option.[29]
- Anti-cytokine therapy, anti-interleukin (IL)-4 and anti-interleukin (IL)-6): Interleukins, particularly IL-4, and IL-6, have been implicated in pemphigus by exacerbating Th2 overexpression and isotype switching to IgG1 and IgG4, which have been shown to play a role in the loss of desmoglein. Direct inhibition of IL-4 and IL-6 is a potential treatment for patients with pemphigus.[30]
- Co-stimulatory and co-inhibitors- manipulators and inhibitors of pathogenic signaling pathways (p38MAPK, c-Myc, and EGFR) are currently being studied and may be targets for novel therapies.[31] (B3)
Differential Diagnosis
- Pyodermatitis pyostomatitis vegetans: Clinically and histologically look similar to pemphigus vegetans but is often associated with inflammatory bowel disease and should have a negative DIF.[32]
- Bullous pemphigoid: Typically presents with tense blisters, urticarial plaques, and pruritus. Mucosal involvement is rare. The histopathological evaluation shows a subepidermal cleft, and DIF shows IgG and/or C3 deposition at the basement membrane. Circulating IgG and IgE autoantibodies are detected against hemidesmosomal proteins.[33][34]
- IgA pemphigus: A subacute autoimmune intraepidermal blistering disease associated with circulating IgA antibodies. DIF shows intracellular IgA deposits within the epidermis.[35]
- Hailey-Hailey Disease: Hailey-Hailey disease is an autosomal dominant genodermatosis that often forms chronic inflammatory plaques in intertriginous areas. The plaques appear as crusted macerated erosions with dry, velvety fissures. Histologic evaluation of the epidermis demonstrates the characteristic “dilapidated brick wall” appearance, which consists of suprabasal clefting and acantholysis.[36][37]
- Pyoderma vegetans: Rare vesiculopustular disease characterized by vegetative plaques with exudate, classically located in the inguinal and axillary folds. It is generally found in immunocompromised patients and is associated with bacterial infections. Histologically, there is pseudoepitheliomatous hyperplasia with sub and intraepidermal microabscesses.[38]
- Paraneoplastic pemphigus: Similar findings to pemphigus vulgaris, often with severe mucosal involvement. It is always associated with underlying malignancy, most commonly a hematopoietic malignancy such as chronic lymphocytic leukemia or other B-cell lymphomas.[39] Anti-periplakin is also associated with paraneoplastic pemphigus.[5][40]
- Epidermolysis bullosa acquisita (EBA): EBA is an autoimmune blistering disease with mucosal involvement. It is caused by circulating autoantibodies against type VII collagen, which is responsible for maintaining the dermal-epidermal junction. The clinical picture is variable, and linear deposits of IgG, IgA, and/or C3 along the dermal-epidermal junction and identification of serum autoantibodies against type VII collagen confirm the diagnosis.[41]
- Porphyria: Porphyrias are genetic diseases of the heme biosynthesis pathway. Porphyria cutanea tarda (PCT) is the commonest, characterized by defective uroporphyrinogen III decarboxylase enzyme. Dermatological manifestations include erosions, vesicles, and bullae in areas exposed to sunlight.[42][43]
- Pemphigus foliaceus (PF): PF is similar to pemphigus vulgaris, but autoantibodies direct their activity against desmoglein (DSG) 1, and it does not involve the mucosal membranes. The blister is often more superficially located in the epidermis.[44]
- Disseminated Herpes infection May cause vesiculobullous eruptions due to viral infection. Histopathological evaluation, viral studies, and culture are key for diagnosis.[4]
- Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN): Spectrum of desquamative disorders characterized by prodromal upper respiratory symptoms, followed by a rash that progresses to full or partial thickness epidermal loss. Most often caused by medication, but it has also been associated with infectious etiologies.[45][46]
- Desquamative gingivitis- may be seen in herpes, oral lichen planus, erythema multiforme, and SJS/TEN.[4]
Prognosis
Autoimmunity is not curable but rather only treated and managed. If untreated, pemphigus, including pemphigus vegetans, can be fatal within 5 years due to severe blistering, secondary infection, and malnutrition. Mortality is approximately 5% to 15% per year.[10]
Complications
Secondary infection of lesions: Staphylococcus aureus, MRSA, herpes, and fungal organisms are most common.
There can be increased susceptibility to systemic infection due to chronic use of immunosuppressive therapies.
Malnutrition due to oral mucosa involvement causes pain, decreased oral intake, and weight loss.
Pap smears may present as dysplastic due to the appearance of acantholytic cells from the cervical and vaginal mucosa.[47]
Consultations
Consultation with a dermatologist is the recommended course for diagnosis and management. Patients on long-term corticosteroids may need endocrinology consultation to manage metabolic side effects.
Deterrence and Patient Education
Pemphigus vulgaris has a known association with myasthenia gravis and thymoma, and patients diagnosed with these conditions are more likely to develop pemphigus.[48]
Patients taking penicillamine or ACE inhibitors (particularly captopril and enalapril) are at increased risk of developing pemphigus. The reported prevalence of pemphigus among patients taking penicillamine is around 7%.[49]
There is a known association between intranasal heroin use and pemphigus vegetans.[50]
Special care should be taken not to pop the blisters; no scrubbing or high-pressure water, as this increases the risk of infection.
Enhancing Healthcare Team Outcomes
All autoimmune diseases require an interprofessional approach for appropriate diagnosis and life-long management. Pemphigus vegetans is a unique variant of pemphigus that is often underrecognized and frequently misdiagnosed. Although it is the rarest form of pemphigus, it is potentially fatal if untreated. Healthcare teams need to work together to recognize and treat patients with this rare form of vesiculobullous autoimmune disease. Because the management of these patients is with a variety of immunosuppressive agents, they need to be educated about the adverse effects and lifelong monitoring. Because of the constant state of suppressed immunity, they also develop bacterial and viral infections. Thus, an infectious disease nurse should follow the patient and monitor for signs of an infection. Pharmacists should verify all dosing and perform medication reconciliation, reporting any concerns to the rest of the healthcare team. Corticosteroids may induce diabetes, so an endocrine consult is necessary. Also, these agents may cause bone thinning, so osteoporosis should be screened to prevent fractures. Many patients develop chronic wounds that fail to heal. Therefore, a wound care nurse should educate the patient on wound care. Only through open communication between the team members can the morbidity and mortality of this severe disorder be reduced.
In summary, pemphigus vulgaris requires an interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists, collaborating across disciplines to achieve optimal patient results. [Level 5]
Outcomes
Unfortunately, despite optimal treatment, the disorder still carries a mortality rate of nearly 10% a year.
References
Basu K, Chatterjee M, De A, Sengupta M, Datta C, Mitra P. A Clinicopathological and Immunofluorescence Study of Intraepidermal Immunobullous Diseases. Indian journal of dermatology. 2019 Mar-Apr:64(2):101-105. doi: 10.4103/ijd.IJD_515_17. Epub [PubMed PMID: 30983604]
von Köckritz A, Ständer S, Zeidler C, Metze D, Luger T, Bonsmann G. Successful monotherapy of pemphigus vegetans with minocycline and nicotinamide. Journal of the European Academy of Dermatology and Venereology : JEADV. 2017 Jan:31(1):85-88. doi: 10.1111/jdv.13779. Epub 2016 Sep 7 [PubMed PMID: 27600093]
Mergler R, Kerstan A, Schmidt E, Goebeler M, Benoit S. Atypical Clinical and Serological Manifestation of Pemphigus Vegetans: A Case Report and Review of the Literature. Case reports in dermatology. 2017 Jan-Apr:9(1):121-130. doi: 10.1159/000468919. Epub 2017 Apr 27 [PubMed PMID: 28559810]
Level 3 (low-level) evidenceJain V,Jindal N,Imchen S, Localized Pemphigus Vegetans without Mucosal Involvement. Indian journal of dermatology. 2014 Mar; [PubMed PMID: 24700958]
Cozzani E, Christana K, Mastrogiacomo A, Rampini P, Drosera M, Casu M, Murialdo G, Parodi A. Pemphigus vegetans Neumann type with anti-desmoglein and anti-periplakin autoantibodies. European journal of dermatology : EJD. 2007 Nov-Dec:17(6):530-3 [PubMed PMID: 17951135]
Level 3 (low-level) evidenceHashimoto K, Hashimoto T, Higashiyama M, Nishikawa T, Garrod DR, Yoshikawa K. Detection of anti-desmocollins I and II autoantibodies in two cases of Hallopeau type pemphigus vegetans by immunoblot analysis. Journal of dermatological science. 1994 Apr:7(2):100-6 [PubMed PMID: 8060912]
Level 3 (low-level) evidenceLangan SM, Smeeth L, Hubbard R, Fleming KM, Smith CJ, West J. Bullous pemphigoid and pemphigus vulgaris--incidence and mortality in the UK: population based cohort study. BMJ (Clinical research ed.). 2008 Jul 9:337(7662):a180. doi: 10.1136/bmj.a180. Epub 2008 Jul 9 [PubMed PMID: 18614511]
Level 2 (mid-level) evidenceMin MS,Damstetter E,Chen AYY, Autoimmune blistering disorders in the setting of human immunodeficiency virus infection. International journal of women's dermatology. 2018 Sep; [PubMed PMID: 30175218]
Suwarsa O, Sutedja E, Dharmadji HP, Kusuma P, Rahardja J, Hindritiani R, Gunawan H. The Rare Case of Pemphigus Vegetans in Association with Malnutrition Children in the Multidisciplinary Management. Case reports in dermatology. 2017 Jan-Apr:9(1):145-150. doi: 10.1159/000473875. Epub 2017 Apr 27 [PubMed PMID: 28559814]
Level 3 (low-level) evidenceEllebrecht CT, Payne AS. Setting the target for pemphigus vulgaris therapy. JCI insight. 2017 Mar 9:2(5):e92021. doi: 10.1172/jci.insight.92021. Epub 2017 Mar 9 [PubMed PMID: 28289723]
Pollmann R, Schmidt T, Eming R, Hertl M. Pemphigus: a Comprehensive Review on Pathogenesis, Clinical Presentation and Novel Therapeutic Approaches. Clinical reviews in allergy & immunology. 2018 Feb:54(1):1-25. doi: 10.1007/s12016-017-8662-z. Epub [PubMed PMID: 29313220]
Sun Y, Liu H, Yang B, Wang C, Foo JN, Bao F, Irwanto A, Yu G, Fu X, Wang Z, You J, Liu J, Zhou G, Liu J, Zhang F. Investigation of the predisposing factor of pemphigus and its clinical subtype through a genome-wide association and next generation sequence analysis. Journal of the European Academy of Dermatology and Venereology : JEADV. 2019 Feb:33(2):410-415. doi: 10.1111/jdv.15227. Epub 2018 Sep 19 [PubMed PMID: 30169916]
Yamagami J. Recent advances in the understanding and treatment of pemphigus and pemphigoid. F1000Research. 2018:7():. pii: F1000 Faculty Rev-1360. doi: 10.12688/f1000research.14474.1. Epub 2018 Aug 30 [PubMed PMID: 30228865]
Level 3 (low-level) evidenceDietze J, Hohenstein B, Tselmin S, Julius U, Bornstein SR, Beissert S, Günther C. Successful and well-tolerated bi-weekly immunoadsorption regimen in pemphigus vulgaris. Atherosclerosis. Supplements. 2017 Nov:30():271-277. doi: 10.1016/j.atherosclerosissup.2017.05.044. Epub 2017 Jun 3 [PubMed PMID: 29096849]
Sillevis Smitt JH, Mulder TJ, Albeda FW, Van Nierop JC. Pemphigus vegetans in a child. The British journal of dermatology. 1992 Sep:127(3):289-91 [PubMed PMID: 1390175]
Level 3 (low-level) evidenceHuang YH,Wang SH,Kuo TT,Chi CC, Pemphigus vegetans occurring in a split-thickness skin graft. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]. 2005 Feb; [PubMed PMID: 15762223]
Level 3 (low-level) evidenceJain VK, Dixit VB, Mohan H. Pemphigus vegetans in an unusual site. International journal of dermatology. 1989 Jun:28(5):352-3 [PubMed PMID: 2753595]
Level 3 (low-level) evidenceGupta VK, Kelbel TE, Nguyen D, Melonakos KC, Murrell DF, Xie Y, Mullard A, Reed PL, Seiffert-Sinha K, Sinha AA. A globally available internet-based patient survey of pemphigus vulgaris: epidemiology and disease characteristics. Dermatologic clinics. 2011 Jul:29(3):393-404, vii-iii. doi: 10.1016/j.det.2011.03.016. Epub [PubMed PMID: 21605804]
Level 3 (low-level) evidenceGerharz M, Stadler R. [Pemphigus vegetans of the Hallopeau type. Detection of pemphigus antibodies with direct and indirect immunofluorescence]. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete. 1987 Jun:38(6):371-4 [PubMed PMID: 3308773]
Level 3 (low-level) evidenceHietanen J, Acantholytic cells in pemphigus. A scanning and transmission electron microscopic study. Acta odontologica Scandinavica. 1982; [PubMed PMID: 6960626]
Yaeen A, Ahmad QM, Farhana A, Shah P, Hassan I. Diagnostic value of Tzanck smear in various erosive, vesicular, and bullous skin lesions. Indian dermatology online journal. 2015 Nov-Dec:6(6):381-6. doi: 10.4103/2229-5178.169729. Epub [PubMed PMID: 26751561]
Ruocco V, Ruocco E, Caccavale S, Gambardella A, Lo Schiavo A. Pemphigus vegetans of the folds (intertriginous areas). Clinics in dermatology. 2015 Jul-Aug:33(4):471-6. doi: 10.1016/j.clindermatol.2015.04.011. Epub 2015 Apr 8 [PubMed PMID: 26051064]
Sawai T, Kitazawa K, Danno K, Sugie N, Machizuki T, Sugiura H, Uehara M. Pemphigus vegetans with oesophageal involvement: successful treatment with minocycline and nicotinamide. The British journal of dermatology. 1995 Apr:132(4):668-70 [PubMed PMID: 7748766]
Level 3 (low-level) evidenceTavakolpour S. Current and future treatment options for pemphigus: Is it time to move towards more effective treatments? International immunopharmacology. 2017 Dec:53():133-142. doi: 10.1016/j.intimp.2017.10.027. Epub [PubMed PMID: 29107213]
Son YM, Kang HK, Yun JH, Roh JY, Lee JR. The neumann type of pemphigus vegetans treated with combination of dapsone and steroid. Annals of dermatology. 2011 Dec:23(Suppl 3):S310-3. doi: 10.5021/ad.2011.23.S3.S310. Epub 2011 Dec 27 [PubMed PMID: 22346265]
Level 3 (low-level) evidenceBaum S, Greenberger S, Samuelov L, Solomon M, Lyakhovitsky A, Trau H, Barzilai A. Methotrexate is an effective and safe adjuvant therapy for pemphigus vulgaris. European journal of dermatology : EJD. 2012 Jan-Feb:22(1):83-7. doi: 10.1684/ejd.2011.1611. Epub [PubMed PMID: 22266247]
Level 2 (mid-level) evidenceMustafi S, Sinha R, Hore S, Sen S, Maity S, Ghosh P. Pulse therapy: Opening new vistas in treatment of pemphigus. Journal of family medicine and primary care. 2019 Mar:8(3):793-798. doi: 10.4103/jfmpc.jfmpc_114_19. Epub [PubMed PMID: 31041203]
Ferraccioli G, Gremese E. B cell activating factor (BAFF) and BAFF receptors: fakes and facts. Clinical and experimental immunology. 2017 Dec:190(3):291-292. doi: 10.1111/cei.13039. Epub 2017 Sep 28 [PubMed PMID: 28834574]
Samy E, Wax S, Huard B, Hess H, Schneider P. Targeting BAFF and APRIL in systemic lupus erythematosus and other antibody-associated diseases. International reviews of immunology. 2017 Jan 2:36(1):3-19. doi: 10.1080/08830185.2016.1276903. Epub [PubMed PMID: 28215100]
Tavakolpour S, Tavakolpour V. Interleukin 4 inhibition as a potential therapeutic in pemphigus. Cytokine. 2016 Jan:77():189-95. doi: 10.1016/j.cyto.2015.09.017. Epub 2015 Oct 2 [PubMed PMID: 26440137]
Mao X, Li H, Sano Y, Gaestel M, Mo Park J, Payne AS. MAPKAP kinase 2 (MK2)-dependent and -independent models of blister formation in pemphigus vulgaris. The Journal of investigative dermatology. 2014 Jan:134(1):68-76. doi: 10.1038/jid.2013.224. Epub 2013 Jun 27 [PubMed PMID: 23657501]
Level 3 (low-level) evidenceHansen LS, Silverman S Jr, Daniels TE. The differential diagnosis of pyostomatitis vegetans and its relation to bowel disease. Oral surgery, oral medicine, and oral pathology. 1983 Apr:55(4):363-73 [PubMed PMID: 6574415]
Level 3 (low-level) evidenceGöbel M, Eming R. [Management of bullous pemphigoid]. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete. 2019 Apr:70(4):236-242. doi: 10.1007/s00105-019-4390-z. Epub [PubMed PMID: 30874841]
Hébert V, Joly P. [Bullous pemphigoid, a dermatosis of the elderly]. La Revue du praticien. 2017 Dec:67(10):1080-1083 [PubMed PMID: 30512605]
Aslanova M, Yarrarapu SNS, Zito PM. IgA Pemphigus. StatPearls. 2023 Jan:(): [PubMed PMID: 30085605]
Patel VM, Rubins S, Schwartz RA, Septe M, Rubins A. Hailey-Hailey disease: a diagnostic challenge. Cutis. 2019 Mar:103(3):157-159 [PubMed PMID: 31039223]
Engin B, Kutlubay Z, Çelik U, Serdaroğlu S, Tüzün Y. Hailey-Hailey disease: A fold (intertriginous) dermatosis. Clinics in dermatology. 2015 Jul-Aug:33(4):452-5. doi: 10.1016/j.clindermatol.2015.04.006. Epub 2015 Apr 8 [PubMed PMID: 26051060]
Meşină C, Vasile I, Mogoantă SŞ, Ciurea ME, Pârvănescu H, Dumitrescu TV, Georgescu CV, Ciobanu D. Pyoderma vegetans of the posterior area of the neck: case presentation. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie. 2015:56(2):563-8 [PubMed PMID: 26193230]
Level 3 (low-level) evidenceRivollier C, Vaillant L, Machet MC, Martin L, Jan V, Huttenberger B, Joly P, Lorette G. [Paraneoplastic pemphigus: a pustular form during chronic lymphoid leukemia]. Annales de dermatologie et de venereologie. 2001 May:128(5):644-8 [PubMed PMID: 11427801]
Level 3 (low-level) evidenceSapadin AN, Anhalt GJ. Paraneoplastic pemphigus with a pemphigus vegetans-like plaque as the only cutaneous manifestation. Journal of the American Academy of Dermatology. 1998 Nov:39(5 Pt 2):867-71 [PubMed PMID: 9810918]
Level 3 (low-level) evidenceVorobyev A, Ludwig RJ, Schmidt E. Clinical features and diagnosis of epidermolysis bullosa acquisita. Expert review of clinical immunology. 2017 Feb:13(2):157-169. doi: 10.1080/1744666X.2016.1221343. Epub 2016 Sep 8 [PubMed PMID: 27580464]
Bulat V, Lugović L, Situm M, Buljan M, Bradić L. Porphyria cutanea tarda as the most common porphyria. Acta dermatovenerologica Croatica : ADC. 2007:15(4):254-63 [PubMed PMID: 18093456]
Handler NS, Handler MZ, Stephany MP, Handler GA, Schwartz RA. Porphyria cutanea tarda: an intriguing genetic disease and marker. International journal of dermatology. 2017 Jun:56(6):e106-e117. doi: 10.1111/ijd.13580. Epub 2017 Mar 21 [PubMed PMID: 28321838]
Mahoney MG, Wang Z, Rothenberger K, Koch PJ, Amagai M, Stanley JR. Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris. The Journal of clinical investigation. 1999 Feb:103(4):461-8 [PubMed PMID: 10021453]
Level 3 (low-level) evidenceNizamoglu M, Ward JA, Frew Q, Gerrish H, Martin N, Shaw A, Barnes D, Shelly O, Philp B, El-Muttardi N, Dziewulski P. Improving mortality outcomes of Stevens Johnson syndrome/toxic epidermal necrolysis: A regional burns centre experience. Burns : journal of the International Society for Burn Injuries. 2018 May:44(3):603-611. doi: 10.1016/j.burns.2017.09.015. Epub 2017 Oct 10 [PubMed PMID: 29029855]
McCullough M, Burg M, Lin E, Peng D, Garner W. Steven Johnson Syndrome and Toxic Epidermal Necrolysis in a burn unit: A 15-year experience. Burns : journal of the International Society for Burn Injuries. 2017 Feb:43(1):200-205. doi: 10.1016/j.burns.2016.07.026. Epub 2016 Aug 21 [PubMed PMID: 27554629]
Kavala M, Topaloğlu Demir F, Zindanci I, Can B, Turkoğlu Z, Zemheri E, Cam OH, Teksen A. Genital involvement in pemphigus vulgaris (PV): correlation with clinical and cervicovaginal Pap smear findings. Journal of the American Academy of Dermatology. 2015 Oct:73(4):655-9. doi: 10.1016/j.jaad.2015.06.057. Epub 2015 Jul 17 [PubMed PMID: 26194705]
Adriano AR, Gomes Neto A, Hamester GR, Nunes DH, Di Giunta G. Pemphigus vegetans induced by use of enalapril. Anais brasileiros de dermatologia. 2011 Nov-Dec:86(6):1197-200 [PubMed PMID: 22281913]
Level 3 (low-level) evidenceBastiaens MT, Zwan NV, Verschueren GL, Stoof TJ, Nieboer C. Three cases of pemphigus vegetans: induction by enalapril--association with internal malignancy. International journal of dermatology. 1994 Mar:33(3):168-71 [PubMed PMID: 8169014]
Level 3 (low-level) evidenceDownie JB, Dicostanzo DP, Cohen SR. Pemphigus vegetans-Neumann variant associated with intranasal heroin abuse. Journal of the American Academy of Dermatology. 1998 Nov:39(5 Pt 2):872-5 [PubMed PMID: 9810919]
Level 3 (low-level) evidence