Subcorneal Pustular Dermatosis Research Articles

Neutrophilic dermatoses

Neutrophilic dermatoses (ND) are a group of inflammatory skin conditions characterized by a neutrophilic infiltrate on histopathology with no evidence of infection. ND are classified based upon the localization of neutrophils within the skin and clinical features. Recent findings suggest that ND are due to two main mechanisms: i) a polyclonal hereditary activation of the innate immune system (polygenic or monogenic); or ii) a clonal somatic activation of myeloid cells such as encountered in myelodysplastic syndrome or VEXAS syndrome. ND belong to internal medicine as a great number of patients with ND suffer from an underlying condition (such as hematological malignancy, inflammatory bowel disease, auto-immune and auto-inflammatory diseases). ND are diagnoses of exclusion and physicians should always consider differential diagnoses, particularly skin infections. Here, we review the pathophysiology and classification of the main ND (i.e., subcorneal pustular dermatosis (Sneddon–Wilkinson Disease) and Intercellular IgA dermatoses, aseptic pustulosis of the folds, Sweet syndrome, neutrophilic eccrine hidradenitis, pyoderma gangrenosum, erythema elevatum diutinum, neutrophilic urticarial dermatosis and neutrophilic panniculitis), their clinical and histopathological features, and we highlight the investigations that are useful to identify ND-associated diseases and to exclude the differential diagnoses.

Subcorneal pustular dermatosis-type IgA pemphigus associated with multiple myeloma: A case report and literature review.

Immunoglobulin A (IgA) pemphigus, also known as intercellular IgA dermatosis, is a rare autoimmune bullous disease presenting with IgA anti-keratinocyte cell surface autoantibodies. Concomitant lymphoproliferative disorders have been reported in IgA pemphigus, including IgA monoclonal gammopathy of undetermined significance and IgA type multiple myeloma (MM). A 35-year-old Japanese woman with a 3-year history of pruritic papulovesicles on her lower legs and trunk was referred to our department. Histopathological examination revealed acantholytic blisters, and results of both direct and indirect immunofluorescence were negative. Direct and indirect immunofluorescence were still negative 3 years and 7months later. Approximately 7 years after her first visit, the patient was re-referred to us because of disease exacerbation. Histopathological findings revealed subcorneal blistering with acantholysis, in which neutrophil-dominant inflammatory cells were present. Indirect immunofluorescence was positive for IgA on the epidermal cell surface and both desmoglein (Dsg) 1/3 and (Dsc) desmocollin 1-3 enzyme-linked immunosorbent assays (ELISAs) for IgA were positive. The histological findings and positive Dsc1 IgA ELISA led to the diagnosis of subcorneal pustular dermatosis (SPD)-type IgA pemphigus. Further examination revealed hyper-IgA globulinemia, increased serum IgA-κ protein, and increased plasma cells in the bone marrow, enabling the diagnosis of IgA type MM. Daratumumab, lenalidomide, and dexamethasone (DLd) therapy was effective for both the MM and the skin lesions, resulting in negative results on Dsg1/3 and Dsc1-3 IgA ELISAs. The association between IgA pemphigus and IgA type multiple myeloma remains unclear, and only seven cases including the present case have been reported. Literature review revealed associations between SPD-type and IgA κ chain in IgA pemphigus and MM, and that in most cases the onset or diagnosis of MM was simultaneous or occurred after the diagnosis of IgA pemphigus. Therefore, clinicians should be aware of the development of multiple myeloma during the clinical course of patients with SPD-type IgA pemphigus.

Line-field confocal optical coherence tomography: a new tool for non-invasive differential diagnosis of pustular skin disorders.

BackgroundThe spectrum of pustular skin disorders (PSD) is large and particularly challenging, including inflammatory, infectious and amicrobial diseases. Moreover, although pustules represent the unifying clinical feature, they can be absent or not fully developed in the early stage of the disease. The line‐field confocal optical coherence tomography (LC‐OCT) is a recently developed imaging technique able to perform a non‐invasive, in vivo, examination of the epidermis and upper dermis, reaching very high image resolution and virtual histology.ObjectivesWe aimed to investigate the potentialities of LC‐OCT in the non‐invasive differential diagnosis of a series of 11 PSD with different aetiology, microscopic features, body location and incidence rates.Materials and MethodsComplete LC‐OCT imaging (i.e. 2D/3D frames, videos) was performed on a total of 19 patients (10 females and 9 males) aged between 35 and 79 years. Images were blindly evaluated and compared with corresponding histopathologic findings.ResultsThe LC‐OCT imaging was able to detect with high accuracy the pustule structure including shape, margins, morphology and cellular content, along with peculiar epidermal and adnexal alterations in each condition, including: Acute Generalized Exanthematous Pustulosis, Generalized pustular psoriasis, Generalized pustular figurate erythema, Subcorneal Pustular Dermatosis, Intraepidermal IgA pustulosis, Palmoplantar pustulosis, Palmoplantar pustular psoriasis. Herpetic whitlow, Acrodermatitis continua of Hallopeau, Vesicopustular Sweet syndrome and Vesicopustular Eosinophilic cellulitis, with pustular appearance, were also compared.ConclusionsThe new LC‐OCT can represent a rapid, non‐invasive and painless tool which can help differentiating among PSD of different aetiology and microscopic morphology in clinical mimickers in daily practice.

Interleukin-17E, inducible nitric oxide synthase and arginase1 as new biomarkers in the identification of neutrophilic dermatoses.

SummaryBackgroundNeutrophilic dermatoses (ND) are a heterogeneous group of diseases, but can often have a relatively similar histological appearance.AimTo identify a combination of biomarkers allowing a better differentiation of ND types.MethodsBiopsies were obtained from normal human skin (NS; n = 4), chronic plaque‐type psoriasis (PsO; n = 7), paradoxical psoriasis (PP; n = 8), generalized pustular psoriasis (GPP; n = 9), subcorneal pustular dermatosis of Sneddon–Wilkinson (SPD; n = 3), acute generalized exanthematous pustulosis (AGEP; n = 3), hidradenitis suppurativa (HS; n = 7), Sweet syndrome (SS; n = 8) and pyoderma gangrenosum (PG; n = 8). Samples were analysed by immunofluorescence using three biomarkers, interleukin (IL)‐17E, inducible nitric oxide synthase (iNOS) and arginase1, each one in combination with two cell markers, myeloperoxidase (MPO) and CD68, which allow the identification of neutrophils and macrophages, respectively.ResultsWe found that SS is characterized by high expression of IL‐17E and iNOS in the epidermis, while PG exhibits low expression. The density of the neutrophil infiltrate helps to differentiate PP (high‐density infiltrate) from PsO (low‐density infiltrate). High expression of arginase1 in the granular layer of the epidermis is a hallmark of SPD. Finally, mature neutrophils and proinflammatory macrophages are readily detectable in PP, SPD and PG, whereas immature neutrophils and anti‐inflammatory macrophages are more frequent in GPP, AGEP, HS and SS.ConclusionsThe analysis of ND by immunofluorescence using IL‐17E, iNOS and arginase1 in combination with MPO and CD68 allows for characterization of differential expression patterns in the epidermis as well as the determination of the polarization status of the dermal neutrophils and macrophages. The appropriate markers may help in the differentiation of ND in clinical practice.

Persistent perianal “warts”

Persistent perianal “warts”

Subcorneal Pustular Dermatosis: A case report of a patient with diffuse scleroderma

Subcorneal pustular dermatosis (SPD) or Sneddon-Wilkinson infection is an uncommon, harmless, constant, sterile pustular ejection which is related with different foundational sicknesses including immunoglobinopathies, neoplasms, and immune system issues. This paper reports an instance of SPD in a patient with diffuse scleroderma in a 37-year-elderly person. The speculation that invulnerable dysregulation might assume a part in the pathogenesis of SPD was assumed by the concurrence of diffuse scleroderma and SPD in our patient.
 CBMJ 2021 January: vol. 10 no. 01 P: 50-53

Papulosquamous annular diseases

Papulosquamous diseases represent a commonly encountered group of cutaneous disorders in dermatology. Lesions can present with papules and plaques in various configurations, including annular forms. Some of these disorders are expected to appear in annular configurations, such as pityriasis rosea and subcorneal pustular dermatosis. Others may either begin as or even progress to annular configurations, including psoriasis vulgaris, seborrheic dermatitis, and nummular dermatitis. We have reviewed common papulosquamous diseases that can present with annular lesions, which includes psoriasis vulgaris, pityriasis rosea, subcorneal pustular dermatosis, contact dermatitis, seborrheic dermatitis, and nummular dermatitis. For each disorder, we have discussed the details of presentation and differential diseases to be considered.

COVID-19 Infection: The Virus and Its Origin, the Variants, the Immune Defense, the Multiorgan Autoimmune Reactions, and the Targeted Treatments

Background: SARS-CoV-2, the virus responsible for the current COVID-19 infection pandemic, has caused substantial damage and negative impacts in the world, including physical sickness, mental illness, death, society lock down, work interruption, and productivity reduction. From the onset in early 2020, the pandemic has not yet totally subsided as of July 2022. Although great efforts have been made to understand the nature of this pandemic by the medical and scientific communities, a comprehensive review of this pandemic has not been reported. Purpose: We aimed to perform a thorough review of the subject in order to come to a better understanding of the origin of the virus, its mutations and their corresponding health effects, its pathophysiology, and its responses to therapeutic intervention. A more comprehensive set of data on these subject matters, if available, would give healthcare providers a valuable tool in formulating the best methods to respond to the current disease and prevent the disease from spreading in the future. Method: An extensive literature search on the subjects of COVID-19 was conducted regarding the possible origin of the viral pathogen, its evolutionary changes and health impacts, the world’s responses to COVID-19 and outcomes of their responses, and healthcare professional’s actions to understand and manage the disease and the results of their actions. To gather these data, websites of PubMed and Google Scholar were utilized for the search with the following keywords: Pandemic, COVID-19, coronavirus, SARS, SARS-CoV, SARS-CoV-2, origin, pathogenesis, and treatment. Results: Our review revealed data that points to an interesting autoimmune phenomenon where most seriously sick patients affected by COVID-19 were documented by an IgA-dominant immune response to the pathogen, along with a neutrophil-directed infiltration to the vital organ in the lung aveola, resulting in critical lung injury, leading to respiratory failure, multi-organ failure, and death. Surprisingly, this IgA-mediated and neutrophil-directed disease pattern is nearly identical to a group of IgA-mediated autoimmune skin diseases, such as dermatitis herpetiformis, IgA bullous dermatosis, and IgA pemphigus, which respond well to treatment by dapsone, a sulfone class of antibiotic/anti-inflammatory drug. Moreover, the usefulness of dapsone was supported by a small clinical study. In addition, systemic corticosteroid, a trusted anti-inflammatory medication, has been used in this pandemic with variable degrees of success. Conclusion: The data collected from our review of the subject, together with our prior search knowledge, compel us to conclude that the underlying pathophysiology that causes serious respiratory distress and multi-organ failure is most likely to be autoimmune in nature and that strategies to counter these multifacet autoimmune disorders would be the most valuable in life-saving. Specifically, we identified clinical and laboratory evidence pointing to IgA autoimmune reaction as a key factor that causes significant mortality in many patients. Accordingly, we proposed the utilization of a combination of dapsone, corticosteroid, and anti-thrombotic drugs in severely ill patients at the earliest point of the disease process. The autoimmune multi-organ syndrome may explain the pathogenesis of COVID-19 as well as Post-COVID conditions and may guide healthcare professionals in a better direction to manage the disease. The possible origin of the viral pathogen may shed light on a better understanding of the pathogenesis of the disease.

An Updated Review of Pemphigus Diseases.

Clinicians may encounter a variety of skin conditions that present with vesiculobullous lesions in their everyday practice. Pemphigus vulgaris, pemphigus foliaceus, IgA pemphigus, and paraneoplastic pemphigus represent the spectrum of autoimmune bullous dermatoses of the pemphigus family. The pemphigus family of diseases is characterized by significant morbidity and mortality. Considering the risks associated with a delayed diagnosis or misdiagnosis and the potential for overlap in clinical features and treatment, evaluation for suspected pemphigus disease often requires thorough clinical assessment and laboratory testing. Diagnosis is focused on individual biopsies for histopathology and direct immunofluorescence. Additional laboratory methods used for diagnosis include indirect immunofluorescence and enzyme-linked immunosorbent assay. Recent advancements, including anti-CD20 therapy, have improved the efficacy and reduced the morbidity of pemphigus treatment. This contribution presents updates on the pathophysiology, clinical features, diagnostic work-up, and medical management of pemphigus. Improved strategies for diagnosis and clinical assessment are reviewed, and newer treatment options are discussed.

Comprehensive review on the pathophysiology, clinical variants and management of pemphigus (Review).

Pemphigus represents a group of chronic inflammatory disorders characterized by autoantibodies that target components of desmosomes, leading to the loss of intercellular adhesion between keratinocytes and causing intraepithelial blistering. The pemphigus group consists of four main clinical types with several variants: pemphigus vulgaris (with pemphigus vegetans and pemphigus herpetiformis as variants), pemphigus foliaceus, paraneoplastic pemphigus and IgA pemphigus (with two clinical variants: intraepidermal neutrophilic IgA dermatosis and subcorneal pustular dermatosis). Genetic factors are involved in the pathogenesis, with HLA-DR4 (DRB1*0402) and HLA-DRw6 (DQB1*0503) allele more common in patients with pemphigus vulgaris, HLA class II DRB1*0344 and HLA Cw*1445 correlated with paraneoplastic pemphigus, and HLA-DRB1*04:01, HLA-DRB1*04:06, HLA-DRB1*01:01, HLA-DRB1*14, associated with a higher risk of developing pemphigus foliaceus. Autoantibodies are conducted against structural desmosomal proteins in the skin and mucous membranes, mainly desmogleins, desmocollins and plakins. Cell-mediated immunity may also play a role, especially in paraneoplastic pemphigus. Patients may present erythema, blisters, erosions, and ulcers that may affect the skin, as well as mucosal surfaces of the oral cavity, eyes, nose, leading to severe complaints including pain, dysphagia, and fetor. Oral mucosal postbullous erosive lesions are frequently the first sign of disease in pemphigus vulgaris and in paraneoplastic pemphigus, without skin involvement, making the diagnosis difficult. Treatment options classically include immunosuppressive agents, such as corticosteroids and corticosteroid-sparing agents such as azathioprine, mycophenolate mofetil, cyclophosphamide, methotrexate or dapsone. Newer therapies focus on blocking cell signaling events induced by pathogenic autoantibodies and/or targeting specific autoantibodies. The disease evolution is conditioned by the treatment with maximum doses of corticosteroids and the side effects associated with long-term immunosuppressive therapy, which is why patients need a multidisciplinary approach in following the treatment. In this review, we provide a comprehensive overview of the epidemiology, pathophysiology, clinical aspect, diagnosis and management of the main intraepidermal blistering diseases from the pemphigus group.

A pemphigus csoport betegségei és terápiás lehetőségei

The diseases of the pemphigus group are chronic conditions belonging to the autoimmune blistering disorders. They appear with characteristic skin and mucous membrane symptoms. Their major forms are pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus. The aim of this review is to present the diseases of the pemphigus group and to summarize the latest therapeutic options with the exception of paraneoplastic and IgA pemphigus that are discussed separately

The epidemiology of autoimmune bullous diseases in Sudan between 2000 and 2016.

Autoimmune bullous diseases vary in their clinico-epidemiological features and burden across populations. Data about these diseases was lacking in Sudan. We aimed to describe the epidemiological profile and to estimate the burden of autoimmune bullous diseases in Sudan. This was a retrospective cross-sectional study conducted at Khartoum Dermatological and Venereal Diseases Teaching Hospital. We used routinely collected health care data, and included all patients with an autoimmune bullous disease who presented to the hospital between 2001 and 2016. Out of the 4736 patients who were admitted to the hospital during the study period, 923 (19.5%) had an autoimmune bullous disease. The average rate of patients at the hospital was 57.7 per year representing 1.3 per 100,000 population per year. After exclusion of patients where the final diagnosis was missing, 585 were included in the further analysis. Pemphigus vulgaris was the most common disease (50.9%), followed by bullous pemphigoid (28.2%), linear IgA disease/chronic bullous disease of childhood (8.4%), and pemphigus foliaceous (8.2%). Pemphigoid gestationis and IgA pemphigus constituted 1.4% and 1.2% of the cohort, respectively. Paraneoplastic pemphigus, mucous membrane pemphigoid, lichen planus pemphigoidis, bullous systemic lupus erythematosus, and dermatitis herpetiformis were rare. None of the patients had epidermolysis bullosa acquisita. The clinico-epidemiological characteristics vary among the types of autoimmune bullous diseases. Females were more predominant in most of them. Sudanese patients tended in general to present at a younger age than other populations. The pool of Sudanese patients with autoimmune bullous diseases is large which requires investigation for the local risk factors and presents a field for future trials.

Pathogenic Activation and Therapeutic Blockage of FcαR-Expressing Polymorphonuclear Leukocytes in IgA Pemphigus

Pathomechanisms in IgA pemphigus are assumed to rely on Fc-dependent cellular activation by antigen-specific IgA autoantibodies; however, models for the disease and more detailed pathophysiologic data are lacking. In this study, we aimed to establish invitro models of disease for IgA pemphigus, allowing us to study the effects of the interaction of anti-keratinocyte IgA with cell surface FcαRs. Employing multiple invitro assays, such as a skin cryosection assay and a human skin organ culture model, in this study, we present mechanistic data for the pathogenesis of IgA pemphigus, mediated by anti-desmoglein 3 IgA autoantibodies. Our results reveal that this disease is dependent on FcαR-mediated activation of leukocytes in the epidermis. Importantly, this cell-dependent pathology can be dose-dependently abrogated by peptide-mediated inhibition of FcαR:IgA-Fc interaction, as confirmed in an additional model for IgA-dependent disease, that is, IgA vasculitis. These data suggest that IgA pemphigus can be modeled invitro and that IgA pemphigus and IgA vasculitis are FcαR-dependent disease entities that can be specifically targeted in these experimental systems.

CPC04: IgA pemphigus, lymphomatoid papulosis and anaplastic large‐cell lymphoma presenting in the same patient: is there a link or is it bad luck?

CPC04: IgA pemphigus, lymphomatoid papulosis and anaplastic large‐cell lymphoma presenting in the same patient: is there a link or is it bad luck?

Pemphigus Vulgaris After COVID-19: a Case of Induced Autoimmunity.

Bullae autoimmune diseases can be induced by environmental factors in a genetically susceptible individual, and viruses may be important triggers for this process. Coronavirus disease 2019 (COVID-19) is a multisystemic disease known for developing many types of skin lesions. However, little is known about post-COVID-19 manifestations. A previous healthy male patient, 43 years old, with resistant mediastinal Hodgkin’s lymphoma stage II diagnosed in 2019, without treatment at the moment, developed monomorphic flaccid bullae on the trunk 40 days after testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although he had risk factors for IgA and paraneoplastic pemphigus, there were no elements for these diseases. The investigation confirmed a pemphigus vulgaris (PV). PV had a good response to treatment with prednisolone 1 mg/kg per day, and methotrexate 15 mg subcutaneously was added per week. The patient was discharged with oral methotrexate and prednisolone at the same dose. Prednisolone was decreased by 20 mg per day during the follow-up. Viruses such as herpesvirus, cytomegalovirus, and varicela zoster can act as triggers for PV. This process is not immediate after the infection because it depends on the change in antibodies initially produced against the virus that start to identify antigens present in the skin’s anchoring structures. SARS-CoV-2 can induce autoimmunity, as seen in Guillán-Barré syndrome and in Kawasaki disease. It is a highly immunogenic virus that is the perfect agent for triggering PV. This case can be considered a cutaneous autoimmune post-COVID-19 manifestation.

Characterizing the presence of neutrophil extracellular traps in neutrophilic dermatoses.

Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of multiple inflammatory dermatoses. However, characterization of NETs in neutrophilic dermatoses was performed on very limited number of patients; this limitation precluded definitive conclusions. In this case series of 57 patients, we compared the amounts of neutrophils producing NETs in cutaneous lesions of different entities of neutrophilic dermatoses (17 with pyoderma gangrenosum, 37 with Sweet's syndrome and three with subcorneal pustular dermatosis). NETs were identified by double immunofluorescence on formalin-fixed paraffin-embedded skin biopsies using antibodies against elastase and citrullinated histone 3. Percentages of neutrophils showing NETs were high across all three entities (62.9% in PG, 48.5% in SS and 37.8% in subcorneal pustular dermatosis). The differences in mean percentages were significant between entities, with PG showing significantly superior percentage of NETs compared with SS. In our series, 15.8% of neutrophilic dermatoses were associated with malignancies, 10.5% with autoimmune diseases and 73.7% were idiopathic. Percentages of NETs were not statistically different between aetiologies. These findings suggest that NETs are abundantly produced in the various entities and different aetiologies of neutrophilic dermatoses. In comparison with SS, the superior percentage of NETs in PG is clinically mirrored in its greater ulceronecrotic nature.

Revisiting the question of pemphigus classification

Analysis of various classifications of pemphigus shows that there are no fundamental differences between them. The main distinctions consist in use of diverse terms in naming of some forms of pemphigus and in inclusion or exclusion of certain subtypes from the classifications. Authors propose to use the following classification in the dermatological clinical practice, for educational and scientific purposes and for clinical guidelines: 1) pemphigus vulgaris (1.1. Pemphigu s vegetans); 2) pemphigus foliaceus (2.1. Pemphigus endemic (Fogo selvagem), 2.2. Pemphigus erythematosus (Senear Usher)); 3) herpetiform pemphigus; 4) paraneoplastic pemphigus; 5) IgA pemphigus (5.1. Subcorneal pustular dermatosis, 5.2. Intraepidermal neutrophilic dermatosis).

Analysis of clinical and diagnostic features and criteria for the effectiveness of treatment of autoimmune bullous dermatoses pemphigus group

The modern classification of autoimmune bullous dermatoses is represented by three groups of diseases that have not only clinical, but also histomorphological, histochemical and immunogenetic similarities. Autoimmune bullous dermatoses are a group of heterogeneous diseases accompanied by the formation of blisters and erosions on the skin and/or mucous membranes under the influence of specific autoimmune complexes. The main clinical manifestations and diagnostic markers of autoimmune bullous dermatoses (ABD) belonging to the pemphigus group are considered.Objective — to analyze the prevalence of clinical forms of pemphigus in the southern region of Ukraine for the period from 2010 to 2020.Materials and methods. The observation group consisted of 88 patients aged 21 to 75 years. The features of clinical manifestations of typical and atypical forms of pemphigus have been studied, a diagnostic algorithm and criteria for the effectiveness of treatment in the early stages of the disease have been developed.Results and discussion. Pemphigus vulgaris was found in 61 (69.3 %), pemphigus vegetans — in 7 (7.9 %), pemphigus erythematosus — in 6 (6.8 %), herpetiform pemphigus — in 4 (4.5 %), IgA pemphigus — in 3 (3.4 %), paraneoplastic pemphigus — in 3 (3.4 %) patients.Conclusions. Modern clinical diagnostic features of ABD (pemphigus group) require the inclusion of immunofluorescence microscopy, direct and indirect enzyme immunoassay in laboratory screening. Not only positive clinical dynamics, but also the rate of disappearance of autoantibodies that induce the diseases (desmoglein, desmoplakin, periplakin, etc.) should be considered the criteria of the effectiveness of treatment of patients with ABD. At the same time, knowledge of the clinical features of ABD and the diseases that mimic them remains an important aspect.

Subcorneal pustular dermatosis associated with IgG monoclonal gammopathy of undetermined significance

Subcorneal pustular dermatosis is a rare chronic relapsing bullous neutrophilic dermatosis. Because it can be associated with monoclonal gammopathy of undetermined significance and multiple myeloma, screening for these conditions is necessary. Herein, we present a case of subcorneal pustular dermatosis, with concurrent monoclonal gammopathy of undetermined significance, successfully treated with acitretin.

Retrospective Analysis of a Single- Kuwaiti Center Clinical Experience Toward Development of Proper Controlling Treatment of 84 Pemphigus Patients with a Long-Term Follow-Up: Efficacy and Safety of the Multidrug Protocol Combining Intravenous Immunoglobulin with the Cytotoxic Immunosuppressor Drugs

Pemphigus is the name of a group of autoimmune pathological entities characterized by the formation of intraepithelial blisters in the skin and/or mucosa. Pemphigus vulgaris (PV) and Pemphigus foliaceus (PF) are considered as classical forms. Rare, non-classical forms of Pemphigus include: Pemphigus herpetiformis, IgA pemphigus, Paraneoplastic pemphigus, IgG/IgA pemphigus. Aim: Aim of our study is to explore the prognostic influence of clinical, immunological and therapeutic drugs on disease course and remission in different pemphigus variants in Kuwait and to establish a safe and effective multidrug protocol. Plan of the study is to make a correlation between epidemiological factors, therapy used and clinical and immunological remission, as well as, follow up of comorbidities in our patients. 84 patients were evaluated, from 1st January 1990 to 31st December 2013. IVIG is used as a third-line adjuvant treatment initially flanked by high-dose systemic corticosteroids and steroid- sparing immune-suppressants. Thus, this multidrug IVIG regimen made it possible to achieve a rapid control of the pemphigus symptoms, with progression to a stable disease remission, while maintenance an overall safety of treatment.