Subcorneal Acantholysis Research Articles

Red crusty plaques in a young man.

Pemphigus foliaceus is a superficial blistering disorder characterized by erosions and scaling in a seborrheic distribution. The condition typically occurs in healthy individuals but issues arise from delayed diagnosis. Many cases remain undiagnosed or misdiagnosed due to the lack of awareness of the condition. With use of common diagnostic tools, pemphigus foliaceus can be easily identified and monitored. Histological analysis exhibits "chicken wire" patterning along keratinocytes in the upper epidermis, whereas immunofluorescence study displays subcorneal acantholysis. Pemphigus foliaceus is confirmed via ELISA studies revealing the presence of autoantibodies against desmoglein 1. Once correctly diagnosed, typically the condition is responsive to corticosteroid therapy. However in recalcitrant cases such as in ours, adjunctive immunosuppressive therapy with dapsone or rituximab may be indicated.

Recalcitrant psoriasiform dermatosis of the face: Is it related to pityriasis rubra pilaris?

There are patients with recalcitrant psoriasiform plaques that do not fit into conventional categories of facial dermatoses. Our study aims to describe the clinicopathological characteristics of several patients with a unique presentation of persistent psoriasiform facial rashes. This retrospective cross-sectional study analyzed clinical and histological data of known cases of recalcitrant psoriasiform dermatosis of the face diagnosed at National Skin Centre, Singapore, over 10 years. There were 8 Chinese patients with mean age at onset of 29 years. Majority had pink to pink-orange well-defined plaques with dry scale (n = 6, 75%), distributed mostly on the cheeks (100%) and chin (n = 7, 88%). Hyperkeratosis, parakeratosis, preserved granular layer and psoriasiform hyperplasia were showed in all biopsies. Other common findings included subtle subcorneal acantholysis, "checkerboard" alternating ortho-/parakeratosis, vacuolated keratinocytes and follicular plugging. All patients showed little treatment response. One patient eventually developed features of type II pityriasis rubra pilaris (PRP). Our study was limited by its small sample size and lack of a pre-existing diagnostic code. This recalcitrant psoriasiform facial dermatosis seems to be a distinct entity, with consistent and reproducible clinical features and a PRP-like histology, bearing some resemblance to the recently described condition-facial discoid dermatosis.

An unusual case of pemphigus erythematosus

Pemphigus erythematosus is characterized by fragile vesicles or bullae, erosions, crusts, and scales in seborrheic area. There are several forms of atypical lesions such as erythematous papules and plaques, verrucous plaques, pustules, and lichenification. Here, we report an atypical pemphigus erythematosus with erythematous papules, plaques, and pustules skin lesions. A 52-year-old Indonesian man presented with prominent pruritic erythematous macules, papules, plaques on the scalp, trunk, and extremities, and also a pustule for each on the back and right arm. Clinically, the patient was diagnosed as small-plaque parapsoriasis, but histopathology examination on the pustule revealed a subcorneal acantholysis and direct immunofluorescence staining showed immunoglobulin G and complement C3 on the cell surface of keratinocytes. These result suitable for pemphigus erythematosus. The patient was treated with topical and systemic corticosteroid, and there were significant improvements in the skin lesions. Pemphigus erythematosus may present with prominent erythematous papules, plaques, and a few pustules. A careful assessment of the clinical manifestation and histopathological findings enabled us to make a correct diagnosis and succesfully treat the patient.

'Hints' in the horn: diagnostic clues in the stratum corneum.

The stratum corneum or horny layer is the uppermost layer of the epidermis, and is mainly responsible for the skin's barrier function. In spite of its complexity at the ultrastructural and molecular level, the features accessible to visualization on conventional histology are relatively limited. Nevertheless, knowledge of subtle clues that one may observe in the stratum corneum can prove useful in a wide range of situations in dermatopathology. We herein review a selection of common and rare entities in which the horny layer may reveal significantly important hints for the diagnosis. These clues include parakeratosis and its different patterns (focal, confluent, alternating, associated with spongiosis, epidermal hyperplasia or lichenoid changes), subcorneal acantholysis, infectious organisms in the stratum corneum (including fungal, bacterial and parasitic), thickening or thinning of the stratum corneum and the presence of different kinds of pigment. Even when normal, the horny layer may prove to be useful when seen in association with severe epidermal damage, a combination of features testifying to the acute nature of the underlying pathological process.

The Incidence of Acantholysis in Pityriasis Rubra Pilaris-Histopathological Study Using Multiple-Step Sections and Clinicopathologic Correlations.

The classical histopathological findings in the epidermis of pityriasis rubra pilaris (PRP) do not include acantholysis; however, acantholysis was described in several case reports and a few series of PRP with variable frequencies. We sought to establish the incidence of acantholysis in biopsies from consecutively referred PRP cases using multiple-step sections and clinicopathologic correlations. Twenty-three biopsies from 12 consecutively referred patients with classical (type 1) PRP were studied histopathologically. Each specimen was completely step sectioned. The clinical files of the patients were also reviewed. Small foci of acantholysis were observed in some of the step sections of 5 of 23 (22%) biopsies obtained from 4 patients. Three biopsies showed suprabasal acantholysis, 1 of which also demonstrated mild dyskeratosis and 2 showed midepidermal acantholytic foci as well. The remaining 2 biopsies demonstrated midepidermal and subcorneal acantholysis, respectively. Small erosions were described in the physical examination of 2 of the 4 (50%) patients with acantholysis and in 1 of the 8 (12.5%) patients without acantholysis. The number of cases. Small foci of acantholysis may be found in the minority of PRP biopsies, and it may be related to small erosions clinically in some patients.

Errata

British Journal of DermatologyVolume 170, Issue 6 p. 1382-1382 ErratumFree Access Errata This article corrects the following: What's in a disease name? E. Sprecher, Volume 170Issue 5British Journal of Dermatology pages: 1005-1007 First Published online: May 19, 2014 First published: 19 June 2014 https://doi.org/10.1111/bjd.13179AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat In the Editorial by Sprecher1, on the example that subcorneal acantholysis has been reported in sinobrachial allergic mycosis syndrome, in page 1005, was incorrect. The correct statement appears below: For example, subcorneal acantholysis has been reported in staphylococcal scalded skin syndrome, caused by a bacterial toxin, in pemphigus foliaceus, caused by autoantibodies and in severe dermatitis, allergic reactions and metabolic wasting (SAM) syndrome, caused by mutations in the desmoglein 1 gene. References 1Sprecher E. What's in a disease name?. Br J Dermatol 2014; 170: 1005– 7. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar Volume170, Issue6June 2014Pages 1382-1382 ReferencesRelatedInformation

PRP with subcorneal acantholysis: case report and review

Although the clinical findings of pityriasis rubra pilaris (PRP) are striking, the microscopic diagnosis can be difficult because changes can be subtle and can overlap with other skin diseases. Suprabasal acantholysis can be seen in PRP, mimicking pemphigus vulgaris. We report a patient with PRP whose initial biopsies demonstrated subcorneal acantholysis mimicking pemiphigus foliaceus.

IgA/IgG Pemphigus: A New Atypical Subset of Pemphigus?

The classical types of pemphigus are well characterized clinically, histologically and immunologically. The tar-get antigens were found to be desmoglein 1 (Dsg1) for pemphigus foliaceus and Dsg3 for pemphigus vulgaris (1). However, there are atypical cases which could not be classified into either of these types. At present two major atypical forms are recognized: pemphigus herpetiformis (PH) (2, 3) and IgA pemphigus with its subsets: subcor-neal pustular dermatosis (SPD) (4–6) and intraepidermal neutrophilic IgA dermatosis (IEN) (7–9).The clinical pattern of PH and IgA pemphigus may to varying degrees resemble dermatitis herpetiformis (eryt-hematous, herpetiform eruption, often in annular arrange-ment). The histological pattern is not characteristic since subcorneal acantholysis may be slight or absent (10). Since the clinical and histological differentiation of PH and IgA pemphigus might be difficult or even not possible, the diagnosis is based on immunological findings: IgG antibodies in PH (3) and IgA antibodies in IgA pemphigus (6, 8, 11). The most interesting problem is coexistence in some cases of both IgA and IgG antibodies, referred to as IgA/IgG pemphigus (12). Since this subset of pemphigus is still not known we present under this name a case with clinical and histological features of PH and immunological pattern of IgA pemphigus of IEN type and reactivity of both IgG and IgA antibodies exclusively to Dsg1.CASE REPORT

Transition from Pemphigus Foliaceus to Pemphigus Vulgaris: Case Report with Literature Review

The transition between the main subtypes of pemphigus, pemphigus vulgaris (PV), and pemphigus foliaceus (PF) has rarely been reported. Moreover, the development of PV in a patient with PF is much more unusual than that of PF in a patient with PV. We report a 48-year-old man who presented with cutaneous lesions showing the typical clinical and histological features of PF. Five years later, his skin lesions became extensive and he developed oral erosions. His condition did not respond well to steroids and azathioprine. Histological examination of a vesicle disclosed suprabasal acantholysis in contrast to the subcorneal acantholysis discovered upon initial histological evaluation. Indirect immunofluorescence revealed IgG antikeratinocyte cell surface antibodies at a titer of 1:640. The titer was 1:160 at initial diagnosis. Upon immunoblotting, the patient's serum reacted with 130 kiloDalton (kDa) and 160 kDa proteins, suggesting desmoglein (Dsg) 3 and 1, respectively. We herein report an unusual case of PV that developed from PF during the disease's flare-up.

Mycophenolate Mofetil as an Adjuvant Therapy for Classic and Endemic Pemphigus Foliaceus

Pemphigus foliaceus is an autoimmune cutaneous disease with subcorneal acantholysis and pathogenic IgG4 autoantibodies directed against desmoglein 1. We present our experience with mycophenolate mofetil (MMF) in the treatment of one case of endemic pemphigus foliaceus (fogo selvagem) and two cases of the classic form. All patients had severe, refractory disease and developed marked adverse effects due to long-term corticosteroid therapy. MMF proved to be an effective corticosteroid-sparing agent at doses varying from 35 to 45 mg/kg/d. It was well tolerated, and we found no significant adverse effects from this drug.

230-kDa and 190-kDa proteins in addition to desmoglein 1 as immunological targets in a subset of pemphigus foliaceus with a combined cell-surface and basement membrane zone immune staining pattern.

Pemphigus erythematosus, initially described as a combination of pemphigus with lupus erythematosus, and pemphigus foliaceus are now frequently considered localized and generalized variants of superficial pemphigus. Yet diagnostic criteria for pemphigus erythematosus remain controversial. Distinct from pemphigus foliaceus, pemphigus erythematosus displays immune depositions at the dermal-epidermal junction, which suggests additional immunopathological mechanisms. We present three patients with clinical and histopathologic signs of superficial pemphigus, who all exhibited an immunomorphology characteristic of pemphigus erythematosus. Complement depositions in a granular-linear fashion were consistently found at the dermal-epidermal junction besides in vivo bound and circulating antikeratinocyte cell-surface autoantibodies. Histopathology showed subcorneal acantholysis, and all sera contained antidesmoglein 1 but not antidesmoglein 3 autoantibodies detected by enzyme-linked immunosorbent assays (ELISA). Additional autoantibodies against a 230-kDa protein and against a 190-kDa protein comigrating with bullous pemphigoid antigen 1 (BP230) and periplakin, respectively, were present in all the patients' sera. As two sera specifically reacted with BP230 by ELISA, the presence of BP230-specific autoantibodies could be associated with dermal-epidermal immune staining in these patients. In pemphigus erythematosus, dermal-epidermal immune staining is generally attributed to the deposition of immune complexes, while the presence of BP230-specific autoantibodies has not been reported in this disease previously. Perhaps, the unique autoantibody profile of the patients in the study permits discrimination between patients with superficial pemphigus that display additional dermal-epidermal immune staining from those with conventional pemphigus foliaceus on a molecular basis. Further studies will be required to substantiate the frequency of this occurrence and to unravel its pathogenic significance.

Desmosomal localization of beta-catenin in the skin of plakoglobin null-mutant mice.

Plakoglobin, a protein belonging to the Armadillo-repeat gene family, is the only component that adherens junctions and desmosomes have in common. Plakoglobin null-mutant mouse embryos die because of severe heart defects and may exhibit an additional skin phenotype, depending on the genetic background. Lack of plakoglobin affects the number and structure of desmosomes, resulting in visible defects when cells are subjected to increasing mechanical stress, e.g. when embryonic blood starts circulating or during skin differentiation. By analysing plakoglobin-negative embryonic skin differentiation in more detail, we show here that, in the absence of plakoglobin, its closest homologue, beta-catenin, becomes localized to desmosomes and associated with desmoglein. This substitution may account for the relatively late appearance of the developmental defects seen in plakoglobin null-mutant embryos. beta-catenin cannot, however, fully compensate a lack of plakoglobin. In the absence of plakoglobin, there was reduced cell-cell adhesion, resulting in large intercellular spaces between keratinocytes, subcorneal acantholysis and necrosis in the granular layer of the skin. Electron microscopic analysis documented a reduced number of desmosomes, and those present lacked the inner dense plaque and had fewer keratin filaments anchored. Our analysis underlines the central role of plakoglobin for desmosomal assembly and function during embryogenesis.

Effect of colchicine in the subcorneal pustular dermatosis type of IgA pemphigus

Background: IgA pemphigus of the subcorneal pustular dermatosis (SPD) type is characterized by subcorneal acantholysis and by an abundance of neutrophils, making colchicine a reasonable pharmacologic option for treatment. Objective: We attempted to determine the efficacy of colchicine in the treatment of SPD-type IgA pemphigus. Methods: Two patients with SPD-type IgA pemphigus were treated with colchicine 1.5 mg/day as monotherapy. Results: A sustained clinical response was achieved within 2 to 3 weeks of therapy. Relapses were noted each time colchicine was stopped. Conclusion: Colchicine should be considered in the treatment of SPD-type IgA pemphigus. (J Am Acad Dermatol 1999;40:91-4.)

Embryonic Heart and Skin Defects in Mice Lacking Plakoglobin

Plakoglobin is the only component common to both the desmosomal plaque and the cadherin–catenin cell adhesion complex in the adherens junction. It is highly homologous to vertebrate β-catenin and toDrosophilaarmadillo protein and may—like these proteins—be also involved in signaling pathways. To analyze the role of plakoglobin during mouse development we inactivated theplakoglobingene by homologous recombination in embryonic stem cells and generated transgenic mice.Plakoglobinnull-mutant embryos died from Embryonic Day 10.5 onward, due to severe heart defects. Some mutant embryos developed further, especially on a C57BL/6 genetic background, and died around birth, presumably due to cardiac dysfunction, and with skin blistering and subcorneal acantholysis. Ultrastructural analysis revealed that here desmosomes were greatly reduced in number and structurally altered. Thus, using reversed genetics we demonstrate that plakoglobin is an essential structural component for desmosome function. The skin phenotype in plakoglobin-deficient mice is reminiscent of the human blistering disease, epidermolytic hyperkeratosis.

Erythema Annulare-like Acantholytic Dermatosis (EAAD): Nonbullous Pemphigus or a New Entity?

This article describes a case of unusual annular erythema-like dermatosis, with histological features of pemphigus foliaceus (subcorneal acantholysis) and IgG antibodies in circulation and bound in vivo to the keratinocyte surface. The reactivity of the antibodies, restricted to human squamous epithelium, was unique, differing from that of all known forms of pemphigus. This also was confirmed by immunoprecipitation. The problem is that these circulating antibodies could be missed if not determined on human substrate. It is to be established whether such cases present a new type of pemphigus or a unknown dermatosis with an autoimmune response of a pemphigus type.

A Vegetating Variety of Pemphigus foliaceus

A 77-year-old man was seen with florid, vegetating nodules in the umbilical, axillary and inguinal areas, scaly erythema in the trunk and fragile nails. Histologically, marked to moderate acanthosis and papillomatosis with intraepidermal abscesses composed of acantholytic cells, eosinophils and neutrophils were seen in the vegetating lesions which showed intercellular IgG deposit by the direct immunofluorescence technique. There were no circulating pemphigus antibodies. The lesions were successfully treated by topical corticosteroids. However, flaccid bullae with hypopyon showing subcorneal acantholysis and intercellular IgG deposits continued to develop. After 3 1/2 years, circulating pemphigus antibody of IgG2 subclass was demonstrated.

Induction of Acantholysis in Organ Explant Culture by Penicillamine and Captopril

Pemphigus is an autoimmune disease proved to be mediated by IgG autoantibodies. Skin lesions clinically and histologically identical to pemphigus may occur in patients receiving penicillamine and captopril, but some of these patients lack circulating or tissue-bound autoantibodies. Therefore, we examined the ability of these drugs to produce acantholysis directly in organ explant culture. Human skin explants were prepared from split-thickness graft skin from adults and from neonatal foreskins. Explants were cultured in media containing 0.1 to 200 mmol/L of penicillamine or captopril; parallel drug-free control cultures were also prepared. Acantholysis occurred in all split-thickness graft skin cultures incubated for 72 hours with at least 20 mmol/L of penicillamine and at 24 to 48 hours in those incubated with at least 10 mmol/L of captopril. Acantholysis occurred less frequently in foreskin cultures, being present in 1 (8%) of 12 of those exposed to at least 20 mmol/L of penicillamine and 3 (12%) of 25 of those exposed to at least 10 mmol/L of captopril. None of the parallel drug-free control cultures developed acantholysis. Subcorneal acantholysis, resembling that seen in pemphigus foliaceus, and suprabasilar acantholysis, resembling that seen in pemphigus vulgaris, were induced in vitro. Our results indicate that both drugs can act as ligands and produce acantholysis in organ explant culture in the absence of autoantibody. This ligand-induced acantholysis may also be responsible for induction of the disease in vivo in those patients who lack demonstrable autoantibodies.

Pemphigus vulgaris and pemphigus foliaceus

The blistering diseases of the skin grouped under the term pemphigus comprise unique organospecific autoimmune disorders in which the epidermis is injured by autoantibodies. The clinical syndromes manifested depend on the specificity of the autoantibodies Present in the patient, i.e., pemphigus vulgaris (PV) autoantibodies produce suprabasilar acantholysis while pemphigus foliaceus autoantibodies cause subcorneal acantholysis. The antigens recognized by these autoantibodies appear to be desmosomal-associated glycoproteins. The etiology of all forms of pemphigus is unknown except for the endemic form of pemphigus foliaceus known as fogo selvagem (PS). FS is thought to be initiated by exposure to environmental factors) present in certain regions of Brazil in which the disease is endemic. This review examines the relevant clinical, histological, and immunologic characteristics of PV and FS. PV is a potentially lethal disease that affects predisposed individuals sharing the HLA-DRw4 and -DRw6 phenotypes and a unique-DQ β-restriction fragment length of the major histocompatibility complex (MHC) polymorphism. Patients develop mucosal erosions and vesicles and bullae in the skin. The majority of patients possess autoantibodies directed against a cell surface antigen of squamous epithelia. The epidermal lesions show suprabasilar acantholysis. Experimental data strongly implicate PV autoantibodies as the cause of the epidermal lesions by mechanisms under current investigation. The IgG fraction from the sera of these patients induces similar lesions when injected into experimental animals. Similarly, F(ab′) 2 but not Fab′ fragments from PV IgG are pathogenic. These findings suggest that cross-linking of a keratinocyte surface antigen by the autoantibodies may be the initial step in the development of acantholysis in the epidermis of patients with PV. FS is a superficial erosive dermatosis that affects young adults and children living in remote villages of certain regions of Brazil where there are more than 15,000 registered cases. Epidemiological data strongly implicate an environmental factor(s) as the cause of FS. If this is established, it would represent a major step forward in the understanding of human autoimmunity. The disease involves only the skin and produces subcorneal vesicles that can lead to exfoliated erythroderma. The majority of patients have autoantibodies against a keratinocyte surface antigen, desmoglein I. These autoantibodies induce epidermal subcorneal vesicles when injected intraperitoneally into experimental animals. FS IgG as well as the F(ab′) 2 and Fab′ fragments are pathogenic when tested in the experimental animal model. This suggests that the autoantibodies in this disease may trigger subcorneal acantholysis by impairing the function of a cell adhesion molecule of the keratinocyte. The mechanisms by which pemphigus autoantibodies precipitate acantholysis continue under investigation in different laboratories. Current experiments suggest that activation of proteases such as plasminogen activator may be implicated in this process. Experimental data from other investigators suggest that complement activation may be an amplifying mechanism of acantholysis. Finally, it has been postulated that pemphigus autoantibodies may impair the assembly of desmosomes, thereby inducing acantholysis. The advances in the immunopathology of pemphigus have proved important in establishing the rationale for the treatment of these patients. All therapies are focused on lowering and eliminating pemphigus autoantibodies from the circulation of the patient. Thus, these therapies for PV and FS (as a prototype of pemphigus foliaceus) include systemic steroid and immunosuppressive agents. As we advance in the understanding of the etiology and pathogenesis of pemphigus, we will be able to develop new approaches in the management of these patients.