Disease burden, clinical management and unmet treatment need of patients with moderate to severe atopic dermatitis; consensus statements, insights and practices from CERTADE (Central/Eastern EU, Russia, Turkiye AD Experts) Delphi panel.

Background: There is limited insight into the current disease burden and everyday clinical management of moderate-to- severe AD in Poland, Czechia, Russia, and Turkiye. Therefore, this study aimed to get information-driven insights regarding the current disease burden and clinical management of patients with moderate-to-severe AD with common and differentiating aspects of the patient journey and establish a consensus. Methods: In this modified 2-round Delphi panel, 133 questions were asked in total to 27 dermatologists. A consensus was achieved when 70% of the panel members strongly agreed or agreed (or strongly disagreed or disagreed) with an item. Statements with <40% agreement dropped from the Delphi rounds and were not repeated. Results: The results state that AD has a significant impact on the quality of life for both patients and their families with social and economic consequences in these countries. While there were significant dissimilarities regarding the current treatment approach by preference order and treatment duration among participants, there was also a high percentage of consensus on literature and guideline-based statements. Current topical therapies and the immune response modifiers were not found to be sufficient by panelists to cover the therapeutic needs of patients with moderate-to-severe AD. Moreover, panelists highlighted the significant burden of adverse events with the off-label use of currently available immunosuppressants. Conclusions: These results underlined that there is a significant disease burden with an unmet treatment need for patients with moderate-to-severe AD in Poland, Czechia, Russia, and Turkiye.

Is There a Need to Educate Patients with Atopic Dermatitis in Baseline Therapy?

INTRODUCTION: The baseline therapy of atopic dermatitis (AD) includes emollient therapy, prevention of triggering factors and proper patients' education. Appropriate level of education about AD among patients is crucial for successful treatment of the disease. AIMS: To compare and evaluate the level of knowledge about baseline therapy in atopic dermatitis (AD) between the adults with AD and the parents of children with AD. MATERIALS AND METHODS: Adult patients with AD (n=180) and parents of children with AD (n=106) completed an original questionnaire covering issues of emollient therapy and bathing. For statistical comparison a chi - square test was used with significance level of 0,05. RESULTS: With significance level of 0,05, the chi - square test showed a statistically significant difference comparing both groups. 52,38% adults and 68,73% parents proved to know the principles of basic therapy (p<0,05). 55,00% adults and 50,00% parents have not been informed how to apply emollients appropriately (p>=0,05). 75,56% and 74,53%, respectively, seek additional education about it (p>=0,05). 63,89% adults and 49,06% parents have not been informed about the principles of bathing (p<0,05). 70,00% and 74,54%, respectively, expect more comprehensive explanation of bathing rules (p>=0,05). CONCLUSIONS: Adults with AD have lesser knowledge about baseline therapy than parents of children with AD. Both groups express a very strong need for education about baseline therapy in AD.

Tape Stripping - Searching for Minimally Invasive Biomarkers in Atopic Dermatitis.

Atopic dermatitis (AD) is nowadays entering a new era of more targeted treatments. However, to make personalized medicine, which we are currently striving for, a reality, a reliable set of validated biomarkers is needed. The most practical seem to be biomarkers that can be obtained easily and minimally invasively. Tape stripping (TS) is a method that provides such an opportunity. This review summarizes the potential biomarkers of AD identified by the minimally invasive TS method. Thymic stromal lymphopoietin (TSLP), interleukin (IL)-13, CC chemokine ligand 17 (CCL17)/thymus and activation-regulated chemokine (TARC) and stratum corneum (SC) lipids can be used as predictive biomarkers for AD occurrence. CCL17/TARC also holds great promise for being reliable biomarkers for AD severity as well as treatment response. Nitric oxide synthase 2 (NOS2)/inducible nitric oxide synthase (iNOS) which high expression is specific for psoriasis may be a good biomarker for differential diagnosis between psoriasis and AD in challenging clinical situations. AD children with food allergy (FA) have a unique endotype characterized by selectively altered expression of various molecules in the skin that can indicate FA coexistence. Unfortunately, although numerous potential biomarkers have been found, none of these candidates have been validated and implemented into routine clinical practice, which still separates us from the possibility of a precise approach to AD patients.

Disease burden, clinical management and unmet treatment need of patients with moderate to severe alopecia areata; consensus statements, insights, and practices from CERTAAE (Central/Eastern EU, Russia, Türkiye AA experts) Delphi panel.

Objectives: This study aims to update the understanding of Alopecia Areata (AA) in Poland, Czechia, Russia, and Türkiye, focusing on the disease burden, clinical management, and patient journey. It seeks to establish a consensus on optimal management strategies for AA in these regions. Methods: A modified 2-round Delphi panel was conveyed with 23 Dermatologists (Russia; 4, Türkiye; 7, Poland; 6, and Czechia; 6). The Delphi questionnaire consisted of 61 statements and 43 questions designed to obtain an overall understanding of the perception and acceptance of available information regarding the care of patients with alopecia areata. Results: The study revealed that moderate-to-severe AA significantly impacts patients' and their families' QoL, consistent with previous studies. AA was found to cause more substantial impairment when additional lesions appeared in visible areas besides the scalp. Work and productivity impairment were notably higher in adults with moderate-to-severe AA. Diagnostic consensus highlighted the importance of skin biopsies and trichoscopy, while the need for more practical severity scoring systems was emphasized. Current treatments, including topical therapies, corticosteroids, and systemic immune modifiers, were deemed insufficient, highlighting the unmet medical need. Conclusion: The Delphi study underscores a significant disease burden and unmet medical needs in patients with moderate-to-severe AA. It highlights the necessity of access to novel treatments and further research to develop more effective therapies with a tolerable safety profile. The findings align with global research, emphasizing the psychosocial impact of AA and the need for standardized, effective treatment protocols.

Gastrointestinal Comorbidities Associated with Atopic Dermatitis-A Narrative Review.

The current understanding of atopic dermatitis (AD) seems to be extending beyond a skin-confined condition frequently associated with allergic comorbidities, as in a number of epidemiological studies, the prevalence rate of a range of illnesses has been determined to be greater in patients with AD, or inversely. In most cases, the reasons for this are vague. A subset of these conditions are gastrointestinal disorders, including food sensitization (FS) and food allergy (FA), eosinophilic esophagitis (EoE) (it is of mixed background, both IgE-dependent and independent), food protein-induced enterocolitis syndrome (FPIES) (it exemplifies an IgE-independent food allergy), Crohn's disease (CD), colitis ulcerosa (CU), celiac disease, irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD). In this review, we performed a comprehensive search of the literature using the PubMed database. We addressed the epidemiology of the increased co-occurrence of these diseases with AD and discussed potential causes for this subject. Multiple gastroenterological comorbidities appear to be more common in patients with AD, according to our review. The mechanisms that underlie this phenomenon are largely unknown, highlighting the need for further study in this field.

Role of acrylates in the development of contact dermatitis in diabetic patients-A Polish dermatology tertiary centre experience.

BACKGROUND: In recent years, an increasing number of contact dermatitis cases triggered by acrylates contained in diabetes medical devices have been reported. Acrylates seem to play a major role in the development of irritant contact dermatitis and allergic contact dermatitis (ACD) in diabetic patients. OBJECTIVES: To study a group of patients with contact dermatitis caused by diabetes medical devices with a focus on acrylates as possible allergens responsible for contact dermatitis. PATIENTS AND METHODS: Fifteen patients with diabetes mellitus type 1 and contact dermatitis from diabetic devices were patch tested to 25 acrylate allergens. RESULTS: Three patients (20%) reacted to the following allergens: three patients reacted to isobornyl acrylate (IBOA) and one of them additionally to 2-hydroxyethyl acrylate (2-HEA); results were of clinical relevance. All three patients were using insulin pumps and glucose sensors (GS)-in one patient contact dermatitis was towards the insulin pump and the GS, in one patient only towards the insulin pump and in one patient only towards the GS. Twelve patients (80%) did not show any skin reaction towards the allergens tested. CONCLUSION: A majority of diabetic patients showed no reactions towards any acrylate allergen tested; yet, the presence of untested allergens must be kept in mind. IBOA proved to be a cause of ACD in diabetes patients. 2-HEA might be another culprit allergen, but its presence in the devices must first be confirmed.

Potential Role of IL-37 in Atopic Dermatitis.

Interleukin 37 (IL-37) is a recently discovered member of the IL-1 cytokine family that appears to have anti-inflammatory and immunosuppressive effects in various diseases. IL-37 acts as a dual-function cytokine, exerting its effect extracellularly by forming a complex with the receptors IL-18 α (IL-18Rα) and IL-1R8 and transmitting anti-inflammatory signals, as well as intracellularly by interacting with Smad3, entering the nucleus, and inhibiting the transcription of pro-inflammatory genes. Consequently, IL-37 is linked to IL-18, which plays a role in the pathogenesis of atopic dermatitis (AD), consistent with our studies. Some isoforms of IL-37 are expressed by keratinocytes, monocytes, and other skin immune cells. IL-37 has been found to modulate the skewed T helper 2 (Th2) inflammation that is fundamental to the pathogenesis of AD. This review provides an up-to-date summary of the function of IL-37 in modulating the immune system and analyses its potential role in the pathogenesis of AD. Moreover, it speculates on IL-37's hypothetical value as a therapeutic target in the treatment of AD.

Erythrodermic Presentation of Atopic Dermatitis in a Patient with Secondary Adrenal Insufficiency Caused by Oral Glucocorticosteroid Abuse.

Dear Editor, A 41-year-old man presented to the Department of Dermatology for the first time due to an exacerbation of atopic dermatitis (AD) in the form of erythroderma. The patient had a history of atopic diseases, with being AD active from infancy. On clinical examination, generalized erythematous skin lesions causing acute pruritus and accompanied by severe skin exfoliation and dryness were present. On closer examination, the patient had a collection of signs and symptoms characterizing Cushing syndrome that included a round and full face (''moon face''), supraclavicular fat pads, and proximal muscle atrophy. The patient stated that AD had exacerbated six years earlier. He had received systemic treatment consisting of methotrexate followed by cyclosporine in another medical facility. However, both medications had proven ineffective and caused malaise. Only oral glucocorticosteroids had proven successful. The patient had been satisfied with the quick and observable effects, and, as he stated, he refrained from regular dermatological visits for six years. During that time, he consistently took 4 mg of methylprednisolone twice daily. Laboratory tests showed undetectably low levels of cortisol, triacylglycerols (TAG) at 288 mg/dL, and total cholesterol levels (CHC) of 81 mg/dL. Based on laboratory findings, clinical presentation, and histopathological evaluation of the skin biopsy, the diagnoses were secondary adrenal insufficiency caused by oral glucocorticosteroid abuse and AD in the form of erythroderma. The endocrinologist suggested a progressive reduction of the dose of methylprednisolone, starting at 2 mg twice daily. Total and sudden drug withdrawal was unacceptable, as it could cause an adrenal crisis. Methylprednisolone was eventually discontinued after being administered for 5 months while the blood levels of ACTH, cortisol, ionized sodium, and ionized potassium were monitored every 4 weeks. 25 mg of hydroxycortisol in divided doses was the actual treatment for adrenal insufficiency, with plans to also gradually reduce the dose. Since the commencement of endocrinological treatment, the dose was reduced to 15 mg after 5 months and to 10 mg after 7 months. Following an 8-month period, the patient began taking 10 mg as needed, usually a few times each month. Calcium carbonate in a dose of 1000 mg taken once daily before a meal for 5 months and vitamin D3 protected the patient from osteoporosis, another manifestation of Cushing syndrome. An initial dose of 4000 IU was prescribed. It is vital to emphasize that all dose adjustments in the endocrinological treatment of Cushing syndrome were a direct consequence of laboratory testing that was performed. In terms of erythrodermic AD management, the patient was treated with cyclosporin, which was once again ineffective. The patient was then prepared for the introduction of dupilumab. A 300 mg dose of the medication was subcutaneously administered every 2 weeks for over a year with positive outcomes, with an initial dose of 600 mg. The patient developed gynecomastia at the beginning of the treatment, initially categorized as another manifestation of Cushing syndrome. However, due to its unilateral nature, it was later identified a benign adverse event of dupilumab, as described in the literature (1). Due to a decline in effectiveness, the treatment was recently switched from dupilumab to baricitinib, with positive outcomes. Erythroderma, which the patient presented in our case, is an acute condition characterized by erythema and scaling that involves more than 90% of the skin's surface area (2,3). It can be potentially fatal due to electrolyte imbalance, fluid loss from capillary dilation, and significant heat dissipation (3). According to estimates, erythroderma is relatively rare, affecting approximately 1-2 patients for every 100,000 people per year, with AD comprising 8.7% of all cases of erythroderma (2,4). Despite growing therapeutic possibilities for AD, corticosteroids remain the drug of choice in severe exacerbations, including erythroderma, when we cannot afford to wait for the effects of therapy. Oral glucocorticosteroids can be an effective treatment for acute flares of AD (5). However, there is a lack of evidence for the long-term efficacy and safety of oral glucocorticosteroids in the treatment of AD (5). Reported side-effects include endocrine disturbances, gastric ulcers, cardiovascular disorders (arterial hypertension, atherosclerotic disease), osteoporosis, glaucoma, cataracts, and an increased risk of infections. Corticosteroids also have an undesired action on the skin that can result in steroid acne, skin atrophy, striae, telangiectasias, hypertrichosis, and impaired wound healing. The psychological adverse effects of steroid treatment can be quite severe and include depression and psychosis (6), The therapy should only be applied in the short-term, not exceeding one week, due to the occurrence of the abovementioned side-effects, which presented in as Cushing syndrome our patient (5). However, glucocorticoids are one of the most commonly used drugs in clinical dermatology practice, raising concerns about the risk of their misuse, which can lead to secondary adrenal insufficiency, among other complications (7). When no other treatment options are available, it should be noted that many of the side-effects of oral glucocorticosteroids can be mitigated through close monitoring and the implementation of appropriate preventive measures (7).

Impact of the COVID-19 Pandemic on Adult Patients with Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic, inflammatory, itchy dermatosis with periods of remissions and exacerbations. Social isolation and lockdown measures may cause increased stress which in turn may affect the skin condition of patients with AD. We aimed to investigate the impact of the COVID-19 pandemic on the course of AD and the mental health of adult patients with AD. The study was based on an anonymous online questionnaire. A total of 91 adult patients with AD participated in this survey. The study population consisted of 77 (84.6%) female and 14 (15.4%) male patients. The average age of patients was 28.3 years. Fifty-four respondents out of 91 (59.3%) noticed a worsening in the course of AD. Patients with worsened AD most often indicated exacerbating itching of the skin (92.6% of 54). Only 54 (59.3%) patients continued treatment as directed by the attending physician. Of those that did not, 13 (14.3%) took or applied fewer medications and 24 (26.4%) stopped taking or applying medications altogether. Of all respondents, 60 (65.9%) believed that their mental health had deteriorated and 11 (12.1%) patients developed suicidal thoughts during the COVID-19 pandemic. The results indicate that the COVID-19 pandemic had a negative impact on the course of AD among adult patients. Forced life changes, increased stress, and poor adherence to treatment may have been contributing factors. Increased stress may have also worsened the mental health of patients with AD, which in turn may have exacerbated AD.

Contact Dermatitis to Diabetes Medical Devices.

Skin adverse reactions to diabetes medical devices have been reported frequently over recent years. Adhesives attaching glucose sensors and continuous insulin infusion sets to the skin are proven to cause both allergic contact dermatitis and irritant contact dermatitis in patients with diabetes mellitus. Several allergens contained in adhesives and/or parts of medical devices are documented to cause allergic contact dermatitis, with acrylate chemicals being the most common culprit-especially isobornyl acrylate (IBOA), but also 2,2'-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate or cyanoacrylates. Epoxy resin, colophonium and nickel were also identified as causative allergens. However, repetitive occlusion, maceration of the skin and resulting disruption of the skin barrier seem to have an impact on the development of skin lesions as well. The purpose of this study is to highlight the burden of contact dermatitis triggered by diabetes medical devices and to show possible mechanisms responsible for the development of contact dermatitis in a group of diabetic patients.

Excess filaggrin in keratinocytes is removed by extracellular vesicles to prevent premature death and this mechanism can be hijacked by Staphylococcus aureus in a TLR2-dependent fashion.

Filaggrin (FLG) protein is indispensable for multiple aspects of the epidermal barrier function but its accumulation in a monomeric filaggrin form may initiate premature keratinocytes death; it is unclear how filaggrin levels are controlled before the formation of storing keratohyalin granules. Here we show that keratinocyte-secreted small extracellular vesicles (sEVs) may contain filaggrin-related cargo providing a route of eliminating excess filaggrin from keratinocytes; blocking of sEV release has cytotoxic effects on those cells. Filaggrin-containing sEVs are found in plasma in both healthy individuals and atopic dermatitis patients. Staphylococcus aureus (S. aureus) enhances packaging and secretion of filaggrin-relevant products within the sEVs for enhanced export via a TLR2-mediated mechanism which is also linked to the ubiquitination process. This filaggrin removal system, preventing premature keratinocyte death and epidermal barrier dysfunction, is exploited by S. aureus which promotes filaggrin elimination from the skin that could help safeguard bacterial growth.

How to Understand Personalized Medicine in Atopic Dermatitis Nowadays?

Atopic dermatitis (AD) is a heterogeneous disease in terms of its phenotypical, barrier, and immunological presentation. Emerging therapies are undoubtedly contributing to a new chapter in the treatment of AD, bringing an excellent possibility of individualization, and thereby creating a tailored approach. The two most promising substance groups are biological drugs (dupilumab, tralokinumab, lebrikizumab, nemolizumab) and Janus kinase inhibitors (JAKis) (baricitinib, upadacitinib, and abrocitinib). The vision that certain well-defined phenotypes and endotypes, as well as personal preferences, may guide the future treatment of AD is both tempting and appealing, but not yet reality. The accessibility of new drugs such as biologics and small molecules has opened up the discussion regarding personalized medicine, referring to the complex nature of AD as well as the experiences from clinical trials and real-world evidence. We have now reached the point of creating new strategies and AD treatment goals by increasing the amount of new information concerning the efficacy and safety of new drugs. This article has reviewed the novel treatment options for AD in the light of the heterogeneity of this disease and proposes a broader vision on the strategy of personalized treatment of AD.

The Associations of Single Nucleotide Polymorphisms of the COL3A1, COL6A5, and COL8A1 Genes with Atopic Dermatitis.

The pathophysiology of atopic dermatitis (AD) is complex, multifactorial, and not fully understood. Genes encoding collagens, the most abundant proteins in the extracellular matrix (ECM), may play a potential role in the pathogenesis of AD. Our study aimed to estimate the associations between Col3A1/rs1800255, Col6A5 /29rs12488457, and Col8A1/rs13081855 polymorphisms and the occurrence, course, and features of AD in the Polish population. Blood samples were collected from 157 patients with AD and 111 healthy volunteers. The genotype distribution of the investigated collagens genes did not differ significantly between the AD and control subjects (p > 0.05). The AA genotype of Col3A1/rs1800255 was significantly associated with the occurrence of mild SCORAD (OR = 0.16; 95% Cl: 0.03-0.78; p = 0.02) and mild pruritus (OR = 18.5; 95% Cl: 3.48-98.40; p = 0.0006), while the GG genotype was significantly associated with severe SCORAD (OR = 6.6; 95% Cl: 1.23-32.35; p = 0.03). Regarding Col6A5/29rs12488457 polymorphism, the average SCORAD score was significantly lower in the group of patients with genotype AA than in patients with the AC genotype (39.8 vs. 53.4; p = 0.04). Nevertheless, both average SCORAD scores were high, and represent the moderate and severe grades of the diseases, respectively. The single nucleotide polymorphisms (SNPs) of COL3A1/ rs1800255 and Col6A5/29rs12488457 seem to be associated with AD courses and symptoms, suggesting new disease biomarkers. The modulation of collagens, the major component of the ECM, may serve as a therapeutic target of AD in the future.

Characterization of Chronic Urticaria and Associated Conditions - A Web-Based Survey.

INTRODUCTION: Chronic urticaria is a common disease, characterized by the development of wheals, angioedema, or both, which can be associated with several comorbidities. Most of the available studies have focused on specific common comorbidities and their association with CU, but have seldom reported the overall burden of comorbidities. OBJECTIVES: This study aimed to investigate and analyze self-reported comorbidities in Polish patients with CU. METHODS: An anonymous online survey consisting of 20 questions was conducted on members of an Urticaria group on the social media platform Facebook. A total of 102 people took part in this survey. The results were analyzed in Microsoft Excel 2016. RESULTS: In the group, 95.1% were females and 4.9% males, with a mean age of 33.8 years. The most common diagnosed type of urticaria was spontaneous (52.9%). Angioedema accompanied urticaria in 68.6% of the respondents, mainly those with delayed pressure urticaria (86.4%). 85.3% of respondents reported comorbidities, most often atopic diseases and allergies (49%), chronic inflammation and infections (36.3%), thyroid (36.3%) and psychiatric disorders (25.5%). Moreover, in 30.4% of patients, at least one autoimmune disease was noted. As compared to the patients without autoimmune urticaria, many more with autoimmune urticaria had a coexisting autoimmune disease (50% vs. 23.7%). Family history of autoimmune diseases was positive in 42.2%, and the familial history of urticaria and atopy was positive in 7.8% and 25.5%, respectively. CONCLUSIONS: The knowledge of comorbidities of chronic urticaria may support clinicians to manage and treat patients with this common condition.

Regnase-1 plays an essential role in maintaining skin immune homeostasis via regulation of chemokine expression.

Regnase-1 is an endoribonuclease that regulates the stability of target genes. Here, we investigated whether Regnase-1 plays a regulatory role in the pathophysiology of atopic dermatitis, a chronic inflammatory skin disease. Regnase-1 levels were decreased in skin and serum of atopic dermatitis patients and mice. Regnase-1+/- mice exhibited more severe atopic dermatitis symptoms than wild-type mice in a house dust mite allergen-induced atopic dermatitis model. Regnase-1 deficiency led to the global changes in gene expression related with innate immune and inflammatory responses, in particular chemokines. The skin Regnase-1 level had an inverse relationship with chemokine expression when we analyzed samples of atopic dermatitis patients and Regnase-1-deficient mice, suggesting that potentiated chemokine production contributes to the augmented inflammation at lesion sites. Subcutaneous administration of recombinant Regnase-1 to mice significantly ameliorated atopic dermatitis-like skin inflammation with reduced chemokine production in a house dust mite-induced atopic dermatitis NC/Nga mouse model. These results indicate that Regnase-1 plays an essential role in maintaining skin immune homeostasis as a regulator of chemokine expression. Modulating Regnase-1 activity may be an efficient therapeutic strategy for treating chronic inflammatory diseases, including atopic dermatitis.

Is Atopic Dermatitis Only a Skin Disease?

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory dermatosis that imposes significant patient and population burdens. In addition to the cutaneous signs and symptoms, growing evidence suggests that AD is systemic in nature. Certain diseases can possibly co-occur with AD as a result of coincidental exposure to similar environmental factors. However, it is also suspected that they are linked to the pathogenesis of AD through more complex genetic and immunological mechanisms, but these correlations remain less understood. It is of great need to seek explanations for the higher frequency of the number of cardiovascular, autoimmune, neurological, psychiatric, and metabolic disorders that have been observed in epidemiologic investigations among AD patients. Moreover, analysing the immunology of chronic inflammation and its correction, activation, or suppression may prevent the development of a variety of comorbidities. As comorbid diseases in patients diagnosed with AD may potentially go undetected, physicians should be aware of them.

Differences in the detection of circulating Hsp90 alpha between patients with atopic dermatitis and dermatitis herpetiformis.

Heat shock protein 90 alpha (Hsp90α) is one of the key intra- and extracellular chaperones responsible for the biological activity of various signaling molecules that are involved in (auto)immune-mediated inflammatory diseases. Recent epidemiologic data suggest that patients with atopic dermatitis (AD) are at risk for several autoimmune diseases, including dermatitis herpetiformis (DH), an extraintestinal manifestation of celiac disease (CD). In addition, pruritic diseases such as AD may be confused clinically with DH. In this study, we aimed to determine the role of circulating Hsp90α in patients with AD in relation to patients with DH, CD, and healthy controls. Using an enzyme-linked immunosorbent assay, levels of circulating Hsp90α were determined in serum samples derived from patients with AD (n = 31), DH (n = 26), CD (n = 15), and healthy controls (n = 55). Although serum concentrations of Hsp90α were similar between patients with DH, CD, and healthy controls, we found that serum levels of Hsp90α were significantly higher (mean value of 5.08-fold; p < 0.0001) in patients with AD when compared to patients with DH. A cutoff value calculated as 2 × standard deviation above the mean concentration of Hsp90α in DH patients revealed that 83.9% (26/31) of AD patients were Hsp90α positive, whereas none of the DH patients (0/26) displayed such a positivity. This preliminary study suggests a distinct role for extracellular Hsp90α in the pathogenesis of AD compared to DH and its potential use in distinguishing AD from DH. Nevertheless, the potential role of the evaluation of extracellular Hsp90α for distinguishing between AD and DH is at present speculative and requires further and careful observations.