Lupus erythematosus-specific bullous lesions.

Lupus erythematosus (LE)-specific bullous lesions are often difficult to distinguish from other bullous diseases presenting in patients with systemic lupus erythematosus. Herein, we describe a 49-year-old woman with systemic lupus erythematosus with recurrent tense bullae on the forearms. Clinical, histopathologic, and serologic findings led to the diagnosis of LE-specific bullous lesions. We also summarize the diagnostic clues for distinguishing LE-specific bullous lesions, bullous systemic lupus erythematosus, and erythema multiforme-like lesions in LE (Rowell syndrome).

Micro-diffusely abnormal white matter: An early multiple sclerosis lesion phase with intensified myelin blistering.

OBJECTIVE: Multiple sclerosis (MS) is a chronic central nervous system disease whose white matter lesion origin remains debated. Recently, we reported subtle changes in the MS normal appearing white matter (NAWM), presenting with an increase in myelin blisters and myelin protein citrullination, which may recapitulate some of the prodromal degenerative processes involved in MS pathogenesis. Here, to clarify the relevance of these changes for subsequent MS myelin degeneration we explored their prevalence in WM regions characterized by subtly reduced myelination (dubbed as micro-diffusely abnormal white matter, mDAWM). METHODS: We used an in-depth (immuno)histochemistry approach in 27 MS donors with histological presence of mDAWM and 5 controls. An antibody panel against degenerative markers was combined and the presence of myelin/axonal aberrations was analyzed and compared with the NAWM from the same cases/slices/regions. RESULTS: mDAWM-defined areas exhibit ill-defined borders, no signs of Wallerian degeneration, and they associate with visible veins. Remarkably, such areas present with augmented myelin blister frequency, enhanced prevalence of polar myelin phospholipids, citrullination, and degradation of myelin basic protein (MBP) when compared with the NAWM. Furthermore, enhanced reactivity of microglia/macrophages against citrullinated MBP was also observed in this tissue. INTERPRETATION: We report a new histologically defined early phase in MS lesion formation, namely mDAWM, which lacks signs of Wallerian pathology. These results support the prelesional nature of the mDAWM. We conceptualize that evolution to pathologically evident lesions comprises the previously documented imbalance of axo-myelinic units (myelin blistering) leading to their degeneration and immune system activation by released myelin components.

Incontinentia pigmenti Stage 1 is not simply vesiculo-bullous but vesiculo-pustular.

Incontinentia pigmenti (IP) is a rare X-linked dominant, male-lethal disorder characterized by pathognomic skin lesions. As described in the literature the typical cutaneous changes follow the pattern of Blaschko's lines and develop in four stages that usually start at birth. Stage 1 is called vesicular, bullous or inflammatory. The vesicles are rapidly filled with eosinophils and thus turn into pustules. Thus, the term "pustular" is relevant to the first phase of IP, and the stage can be considered as "vesiculopustular/inflammatory" to be more precise than "vesicular" or "bullous."

Advancements in Bullous Pemphigoid Treatment: A Comprehensive Pipeline Update.

ABASTRACT: Bullous pemphigoid (BP) is a common autoimmune bullous disease affecting mainly the elderly, with rising incidence due to increased life expectancy. This disease is characterized by tense bullous lesions on normal or erythematous skin, accompanied by pruritus. BP pathogenesis involves autoantibodies against hemidesmosomal proteins BP180 and BP230, leading to detachment at the dermo-epidermal junction as well as blister formation. BP is associated with coexisting comorbidities and drug exposure, and its management often requires high doses or chronic use of systemic glucocorticoids, posing risks of adverse effects. This review focuses on novel treatment options for BP, exploring therapies targeting different immune pathways. Rituximab, a CD20 monoclonal antibody, depletes B-lymphocytes and has shown efficacy in severe cases. Dupilumab, targeting interleukin (IL)-4 receptor α and thus blocking IL-4 and IL-13, downregulates type 2 helper (Th2) responses and has demonstrated promising results. Targeting eosinophil-related molecules using bertilimumab and AKST4290 has yielded positive results in clinical trials. Omalizumab, an immunoglobulin (Ig) E antibody, can reduce disease severity and allows corticosteroid tapering in a number of cases. Complement inhibitors such as nomacopan and avdoralimab are being investigated. IL-17 and IL-23 inhibitors such as secukinumab and tildrakizumab have shown potential in a limited number of case reports. Neonatal Fc receptor antagonists such as efgartigimod are under investigation. Additionally, topical therapies and Janus kinase inhibitors are being explored as potential treatments for BP. These novel therapies offer promising alternatives for managing BP, with potential to improve outcomes and reduce high cumulative doses of systemic corticosteroids and related toxicities. Further research, including controlled clinical trials, is needed to establish their efficacy, safety, and optimal dosing regimens for BP management.

Diagnostic Techniques in Autoimmune Blistering Diseases.

Autoimmune blistering diseases (AIBD) comprise a heterogeneous group of uncommon disorders of the skin and mucous membranes, characterised by antibodies targeting structural proteins within epithelial tissue and the underlying basement membrane. There can be significant overlap in clinical presentation of these diseases and accurate diagnosis relies on the detection and characterisation of relevant autoantibodies. Immunofluorescence provides the gold-standard diagnostic tool for these diseases, identifying both tissue-bound autoantibodies in biopsy material using direct immunofluorescence and circulating antibodies in serum through indirect immunofluorescence. Following advances in the identification and subsequent characterisation of numerous antigenic targets in these diseases, the development of antigen-specific tests, in particular, enzyme-linked immunosorbent assays on serum specimens, has provided a third key tool to not only identify, but also quantify AIBD autoantibodies. This quantification has proven particularly useful in monitoring disease activity and informing clinical management decisions. Accurate diagnosis of these diseases is important since optimal treatment strategies differ between them and, prognostically, some diagnoses are associated with an increased risk of malignancy. This review outlines the molecular pathology underlying the major AIBD and describes how the three principal techniques can be used in combination, to provide best practice for diagnosis and treatment monitoring.

Eosinophil-derived galectin-10 upregulates matrix metalloproteinase expression in bullous pemphigoid blisters.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune bullous disease in which abundant eosinophils accumulate in the blisters. Galectin-10 abounds in the cytoplasm of eosinophils and is released as a result of eosinophil extracellular trap cell death (EETosis). OBJECTIVE: To identify EETosis and the pathological roles of galectin-10 in BP. METHODS: EETosis and galectin-10 in BP blisters were confirmed by immunofluorescence and transmission electron microscopy. The concentrations of galectin-10 in serum and blister fluid from BP patients were studied by ELISA. The matrix metalloproteinase (MMP) expression in BP blisters was immunohistochemically compared to that in healthy controls. As an in vitro assay, normal human epidermal keratinocytes (NHEKs) and normal human dermal fibroblasts (NHDFs) were stimulated with galectin-10, followed by MMP expression measurement by real-time PCR and ELISA. The signaling pathways activated by galectin-10 were studied using Western blotting and confirmed by inhibition assays. RESULTS: Galectin-10-containing eosinophil infiltration and the extracellular deposition of major basic protein were observed in BP blisters. The ultrastructural characteristics of tissue eosinophils indicated piecemeal degranulation and EETosis. In the BP patients, the concentration of galectin-10 was higher in the blister fluid than in the serum. Several types of MMPs were upregulated in BP blisters. Galectin-10 upregulated the production of MMPs through the pathways of p38 MAPK, ERK and JNK in NHEKs and NHDFs. CONCLUSION: In the BP blisters, the eosinophils underwent EETosis and released galectin-10. Galectin-10 might contribute to BP blister formation through the production of MMPs by keratinocytes and fibroblasts.

Necrotizing fasciitis - a complication of autoimmune skin blistering diseases?

INTRODUCTION: Autoimmune bullous diseases (AIBD) are organ-specific skin blistering diseases clinically manifesting as bullae and vesicles of the skin and mucous membranes. The loss of skin barrier integrity renders patients susceptible to infection. Necrotizing fasciitis (NF), a rare yet severe infectious complication of AIBD has been insufficiently documented in the literature. CASE REPORT: We present a case of a 51-year-old male patient with NF initially misdiagnosed as herpes zoster. Given the local status, CT imaging, and laboratory parameters, NF diagnosis was made and the patient was taken for an urgent surgical debridement. In a further development, new bullae in remote areas erupted and a perilesional biopsy, direct immunofluorescence as well as local status, the patient's age, and atypical presentation, imposed an initial diagnosis of epidermolysis bullosa acquisita. Differential diagnoses were bullous pemphigoid (BP) and bullous systemic lupus. In the literature, 9 other described cases were found and are reviewed. CONCLUSIONS: Due to its unspecific clinical picture, necrotizing fasciitis itself presents a frequently misdiagnosed soft tissue infection. Altered laboratory parameters in immunosuppressed patients often lead to misdiagnosing of NF and loss of precious time, which plays a major role in survival. Given the manifestation of AIBD as loss of skin integrity and immunosuppressive therapy, these patients could be more predisposed to NF than the general population.

Histopathological characterisation of trunk-dominant canine pemphigus foliaceus, and comparison with classic facial and insecticide-triggered forms.

BACKGROUND: While the clinical features were described recently, the histopathological characterisation of trunk-dominant canine pemphigus foliaceus (PF) is lacking, and whether it differs from classic facial or insecticide-triggered PF is unknown. HYPOTHESIS/OBJECTIVES: This study describes the histopathological findings of trunk-dominant PF, and compares the results to classic facial and insecticide-triggered PF. ANIMALS: Skin biopsies from 103 dogs with clinically characterised trunk-dominant (n = 33), classic facial (n = 26) and insecticide-triggered PF (n = 44) were included. MATERIALS AND METHODS: Histological sections, randomised and blinded, were scored for over 50 morphological parameters of pustules, epidermis, dermis, adnexa and crusts. Intact pustule area and width were measured by digital microscopy. RESULTS: In trunk-dominant PF, 77 intact pustules were predominantly subcorneal (0.0019-1.940 mm2 area, 0.0470-4.2532 mm wide), and contained from one to over 100 acantholytic keratinocytes. Pustules had boat acantholytic cells, corneocytes, perinuclear eosinophilic rings, neutrophil rosettes, acantholytic cell necrosis, rafts, cling-ons and/or eosinophils. Peripustular epidermal spongiosis, necrosis and lymphocyte exocytosis occurred, as did follicular pustules. Mixed dermal inflammation often contained eosinophils. Trunk-dominant PF did not differ from the other PF groups except for few parameters, such as having fewer rafts (p = 0.003). Additional autoimmune inflammatory patterns occurred in all PF groups. CONCLUSIONS AND CLINICAL RELEVANCE: Trunk-dominant PF and other canine PF variants are histologically similar, which indicates shared pathomechanisms. The identification of common boat acantholytic cells and corneocyte separation has implications for the mechanisms of acantholysis. The diversity of histopathological and polyautoimmunity features support complicated immune mechanisms. Finally, results indicate that diagnostic biopsies cannot differentiate between these PF variants in dogs.

Three cases of subcorneal pustular dermatosis with immunohistochemical examinations.

Subcorneal pustular dermatosis, a rare, benign skin disease, is a type of neutrophilic dermatosis. The authors reported three cases of subcorneal pustular dermatosis. In case 1, a 9-year-old girl developed a skin rash with blisters following a mycoplasma infection and had a flare-up due to a common cold. She was successfully treated with a topical corticosteroid. In case 2, a 70-year-old woman who had been treated for rheumatoid arthritis with adalimumab, salazosulfapyridine, and leflunomide developed 3- to 5-mm pustules on her trunk and thighs 4 days after flu vaccination. The rash disappeared with drug withdrawal and treatment with diaminodiphenyl sulfone. In case 3, an 81-year-old man, who was diagnosed with pyoderma gangrenosum at 61 years old, developed multiple small flaccid pustules on his trunk and extremities due to an infection in the arteriovenous shunt area on the forearm. The pustule disappeared with intravenous antibiotic therapy; however, the pustules subsequently flared up along with ulcers typical of pyoderma gangrenosum. He was given oral prednisolone therapy, which was effective for the small pustules and some ulcers. Immunohistochemical examination of the three cases revealed neutrophilic infiltration in the subcorneal layer of the epidermis. The pustules contained neutrophils as well as some CD68+ and a few CD1a+ cells. The epidermis and dermis were more predominantly infiltrated by CD4+ cells than by CD8+ cells. Positive stainings for interleukin 8, interleukin 36γ, and phospho-extracellular signal-regulated kinases 1 and 2 were observed in the upper layers of the epidermis below the pustules. Although the pathogenesis of subcorneal pustular dermatosis has not been clarified, the current results suggest that a variety of inflammatory cells, including those responsible for both innate and acquired immunity, are involved in the accumulation of neutrophils in subcorneal pustular dermatosis.

Mouse models of pemphigus: valuable tools to investigate pathomechanisms and novel therapeutic interventions.

Autoimmune blistering diseases (AIBD) are paradigms of autoantibody-mediated organ-specific autoimmune disorders that involve skin and/or mucous membranes. Compared to other autoimmune diseases, the pathogenicity of autoantibodies in AIBD is relatively well described. Pemphigus is a potentially lethal autoantibody driven autoimmune disorder with a strong HLA class II association. It is mainly characterized by IgG against the desmosomal adhesion molecules desmoglein 3 (Dsg3) and Dsg1. Several murine pemphigus models were developed subsequently, each allowing the analysis of a characteristic feature, such as pathogenic IgG or Dsg3-specific T or B cells. Thus, the models can be employed to preclinically evaluate potentially novel therapies. We here thoroughly summarize past and recent efforts in developing and utilizing pemphigus mouse models for pathomechanistic investigation and therapeutic interventions.

Development of a Skin-Directed Scoring System for Stevens-Johnson Syndrome and Epidermal Necrolysis: A Delphi Consensus Exercise.

Importance: Scoring systems for Stevens-Johnson syndrome and epidermal necrolysis (EN) only estimate patient prognosis and are weighted toward comorbidities and systemic features; morphologic terminology for EN lesions is inconsistent. Objectives: To establish consensus among expert dermatologists on EN terminology, morphologic progression, and most-affected sites, and to build a framework for developing a skin-directed scoring system for EN. Evidence Review: A Delphi consensus using the RAND/UCLA appropriateness criteria was initiated with a core group from the Society of Dermatology Hospitalists to establish agreement on the optimal design for an EN cutaneous scoring instrument, terminology, morphologic traits, and sites of involvement. Findings: In round 1, the 54 participating dermatology hospitalists reached consensus on all 49 statements (30 appropriate, 3 inappropriate, 16 uncertain). In round 2, they agreed on another 15 statements (8 appropriate, 7 uncertain). There was consistent agreement on the need for a skin-specific instrument; on the most-often affected skin sites (head and neck, chest, upper back, ocular mucosa, oral mucosa); and that blanching erythema, dusky erythema, targetoid erythema, vesicles/bullae, desquamation, and erosions comprise the morphologic traits of EN and can be consistently differentiated. Conclusions and Relevance: This consensus exercise confirmed the need for an EN skin-directed scoring system, nomenclature, and differentiation of specific morphologic traits, and identified the sites most affected. It also established a baseline consensus for a standardized EN instrument with consistent terminology.

Usefulness of immunofluorescence overlay antigen mapping in the identification of autoantigen in anti-p200 pemphigoid.

Anti-p200 pemphigoid is a rare subepidermal blistering disease showing immunoglobulin G (IgG) autoantibodies reactive with a 200-kDa protein. In most patients, serum IgG antibodies react with laminin γ1. The diagnosis of anti-p200 pemphigoid is occasionally difficult, mainly due to the lack of standardized tests. We performed fluorescence overlay antigen mapping by laser scanning confocal microscopy (FOAM-LSCM) to identify autoantigens in an anti-p200 pemphigoid patient and assessed its usefulness for the diagnosis. A 71-year-old man presented with blisters and erosions on the bilateral forearms. No mucosal lesions were observed. Laboratory examinations revealed mild leukocytosis and antinuclear antibody negativity. A histopathological examination showed subepidermal blisters with neutrophil infiltration. Direct immunofluorescence showed linear IgG staining along the basement membrane zone. Indirect immunofluorescence using 1 M NaCl-split skin sections revealed IgG reactivity on the dermal side. Immunoblotting detected circulating IgG autoantibodies that reacted with a 200-kDa protein. Accordingly, anti-p200 pemphigoid was diagnosed. FOAM-LSCM revealed that the patient's IgG signals were co-localized with laminin γ1 but were observed above type VII collagens. A direct immunofluorescent analysis for IgG deposition patterns showed an n-serrated pattern. Thus, FOAM-LSCM may be useful for diagnosing anti-p200 pemphigoid.

Giant and potentially malignant bullae in a dog.

Background: Primary lung neoplasms are, frequently represented by solid, solitary, or multiple formations. However, malignant cavitary lesions may be presented as lung adenocarcinomas. Those malignant lesions differ from benignant bullae by the thickness heterogeneity of its surrounding shape. Case Description: The present clinical case reports a 14-year-old female dog, of mixed breed, with an increase in the coughs frequency, fatigue, and exercise intolerance. A chest X-ray was taken, a large emphysematous cystic area was found, with thickened and irregular walls located in the left caudal pulmonary lobe, which measured 8 × 7.5 × 3 cm, and rejected the bronchial branch corresponding to the left caudal pulmonary lobe, in addition to thickening of the bronchial walls, compatible with bronchopathy. The tomographic examination of the cavity showed an air content structure, oval to round in shape, with irregular thick hyperattenuating walls measuring approximately 0.4 cm in thickness, occupying more than 30% of the left hemithorax, and pulmonary lobectomy was chosen. Histopathology confirmed the diagnosis of bronchoalveolar adenocarcinoma, with the presence of sparse areas of necrosis and dystrophic calcification. Conclusion: The present case successfully diagnosed a malignant bulae, after a surgical remove. The tomographic finds although not confirmatory, suggest a malignant component by the shape and thickness of its wall. The tomographic exam is of great importance, because only through it, it is possible to evaluate if there is lymph node or pleural involvement or the presence of small metastasis foci. There is indication for surgery and histopathological examination of the piece for a definitive diagnosis.

Autoimmune Skin Conditions: Autoimmune Blistering Disease.

There are many types of autoimmune blistering skin disease. Two of the most common are bullous pemphigoid and pemphigus vulgaris. Bullous pemphigoid is characterized by tense bullae created by a subepidermal split resulting from autoantibodies targeted at the hemidesmosomes at the dermal-epidermal junction. Bullous pemphigoid typically occurs in elderly people and often can be drug-induced. Pemphigus vulgaris is characterized by flaccid bullae because of an intraepithelial split triggered by autoantibodies targeting desmosomes. Diagnosis can be made for both conditions by physical examination, biopsy for routine histology, biopsy for direct immunofluorescence, and serologic studies. Both bullous pemphigoid and pemphigus vulgaris are associated with significant morbidity and mortality and diminished quality of life, making early recognition and diagnosis paramount. Management proceeds in a stepwise approach using potent topical corticosteroids along with immunosuppressant drugs. Rituximab recently has been shown to be the drug of choice for most people with pemphigus vulgaris.

Selected genodermatoses - Status quo and future prospects.

Genodermatoses are monogenetic disorders, which may manifest with symptoms either exclusively on the skin or also involve other organs in the context of an associated syndrome. Over the past 30 years, numerous hereditary hair, tumor, blistering, and keratinization diseases have been characterized both clinically and genetically. This has resulted in the continuous development of disease-specific classifications as well as diagnostic algorithms and examination techniques, and has also led to new pathogenesis-based therapeutic approaches. While the deciphering of the underlying genetic defects of these diseases is already well advanced, there is still much room for the development of new translationally motivated treatment strategies.

Treatment of corneal ulceration and bullous keratopathy using a nictitating membrane flap in two horses.

OBJECTIVE: The aim of this study was to describe placement of a nictitating membrane flap as a treatment for corneal ulceration and bullous keratopathy in two horses. ANIMALS STUDIED: A 13-year-old American Saddlebred mare presented for severe corneal edema, superficial stromal ulceration, and a central bulla of the left eye. A 4-year-old Trakhener stallion also presented with a large axial bulla of the left eye with concurrent severe corneal edema and a deep stromal ulcer. PROCEDURE: A complete ophthalmic examination was performed. Samples were obtained for corneal cytology, and both horses were started on aggressive medical therapy. Both underwent general anesthesia for placement of a nictitating membrane flap and a subpalpebral lavage system (SPLS). RESULTS: Corneal cytology for each horse revealed a mixed bacterial population. Moderate Pseudomonas aeruginosa was cultured from the mare, while Aspergillus species and a few Enterococcus gallinarum were cultured from the stallion. The bullae in both horses resolved at 3 and 4 weeks and vision returned in the affected eye 4.5 and 3 months postoperatively at the last follow-up, respectively. CONCLUSION: Aggressive medical management with concurrent placement of a nictitating membrane flap is effective to treat bullous keratopathy in two horses. The described treatments could be used to treat horses that develop severe or progressive bullous corneal lesions.

Distinguishing annular pustular psoriasis from subcorneal pustular dermatosis-A diagnostic dilemma in a 10-year-old boy.

Subcorneal pustular dermatosis (SPD) and annular pustular psoriasis (APP) are very rare in childhood and difficult to differentiate both clinically and histopathologically. We report the case of a 10-year-old male with a 9-year history of erythematous scaly annular plaques with scattered pustules on the trunk. Although initially diagnosed as SPD, a lack of response to dapsone, presence of spongiosis on histology, and early age of disease onset led to consideration of APP. The patient was subsequently treated with adalimumab 80 mg weekly and completely cleared. This case illustrates the overlapping features of SPD and APP and suggests that the two disorders may represent a spectrum of the same disease.

Vesiculobullous and Other Cutaneous Manifestations of COVID-19 Vaccines: a Scoping and Narrative Review.

As coronavirus disease (COVID-19) vaccines continue to be administered, dermatologists play a critical role in recognizing and treating the cutaneous manifestations (CM) associated with the vaccines. Adverse cutaneous reactions of COVID-19 vaccines reported in the literature range from common urticarial to rare vesiculobullous reactions. In this study, we performed a (1) scoping review to assess the occurrences of vesicular, papulovesicular, and bullous CMs of COVID-19 vaccines and their respective treatments, and (2) a narrative review discussing other common and uncommon CMs of COVID-19 vaccines. Thirty-six articles were included in the scoping review, and 66 articles in the narrative review. We found that vesicular, papulovesicular, and bullous lesions are infrequent, reported mostly after the first dose of Moderna or Pfizer vaccines. Eleven of the 36 studies reported vesicular reactions consistent with activation or reactivation of the herpes zoster virus. Most vesicular and bullous lesions were self-limited or treated with topical corticosteroids. Other CMs included injection-site, urticarial or morbilliform reactions, vasculitis, toxic epidermal necrolysis, and flaring of or new-onset skin diseases such as psoriasis. Treatments for CMs included topical or oral corticosteroids, antihistamines, or no treatment in self-limited cases. Although most CMs are benign and treatable, the data on the effect of systemic corticosteroids and immunosuppressive therapies on the immunogenicity of COVID-19 vaccines is limited. Some studies report reduced immunogenicity of the vaccines after high-dose corticosteroids use. Physicians may consult local guidelines where available when recommending COVID-19 vaccines to immunosuppressed patients, and when using corticosteroids to manage the CMs of COVID-19 vaccines.

Lymphocyte-predominant lesional inflammatory infiltrates of the skin are associated with mucosal-dominant phenotype in pemphigus.

INTRODUCTION: Pemphigus is a potentially life-threatening autoimmune blistering disease. To date, studies assessing the association of histopathology with clinical phenotype are lacking. We sought to evaluate the main histopathologic findings and, also, the potential links between cutaneous inflammatory infiltrates and clinical characteristics in pemphigus. METHODS: We conducted a retrospective cohort study in patients diagnosed with pemphigus vulgaris (PV) and pemphigus foliaceus (PF) in a referral center for autoimmune blistering diseases. RESULTS: A total of 124 patients were included in the study (97 had PV and 27 had PF). On biopsy specimens, PV was more frequently associated with the "row of tombstones" feature (36.1% vs. 11.1%, p = 0.013), and PF was associated with acanthosis (44.4% vs. 23.7%, p = 0.034). Acantholysis was found in the upper half of the epidermis in PF (96.3% vs. 5.15%, p < 0.001), as opposed to the lower half in PV (75.2% vs. 0%, p = 0.002). Patients with lymphocyte-predominant inflammatory infiltrates in lesional skin specimens presented with a higher frequency of the mucosal-dominant phenotype (25.5% vs. 9.1%, p = 0.014), higher-density cellular infiltrate (100% vs. 41.6%, p < 0.001), and more frequent acantholytic cells (42.6% vs. 23.4%, p = 0.025). Neutrophil-predominant infiltrates in specimens from lesional skin were linked to a milder disease based on median Pemphigus Disease Area Index (38.9% vs. 13.2%, p = 0.036) and Autoimmune Bullous Skin Disorder Intensity Score (20.2 vs. 36.3, p = 0.019), while eosinophil-predominant inflammatory infiltrates were more often associated with eosinophilic spongiosis (100% vs. 23.1%, p = 0.014). CONCLUSIONS: Lymphocyte-predominant infiltrates in lesional skin specimens of pemphigus patients predict a mucosal-dominant phenotype, while neutrophil-predominant infiltrates are associated with a milder disease.