A case of autoimmune pulmonary alveolar proteinosis during the course of treatment of rapidly progressive interstitial pneumonia associated with anti-MDA5 antibody-positive dermatomyositis.

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (APAP) is a diffuse lung disease that causes abnormal accumulation of lipoproteins in the alveoli; however, its pathogenesis remains unclear. Recently, APAP cases have been reported during the course of dermatomyositis. The combination of these two diseases may be coincidental; however, it may have been overlooked because differentiating APAP from a flare-up of interstitial pneumonia associated with dermatomyositis is challenging. This didactic case demonstrates the need for early APAP scrutiny. CASE PRESENTATION: A 50-year-old woman was diagnosed with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatitis and interstitial pneumonia in April 2021. The patient was treated with corticosteroids, tacrolimus, and cyclophosphamide pulse therapy for interstitial pneumonia complicated by MDA5 antibody-positive dermatitis, which improved the symptoms and interstitial pneumonia. Eight months after the start of treatment, a new interstitial shadow appeared that worsened. Therefore, three additional courses of cyclophosphamide pulse therapy were administered; however, the respiratory symptoms and interstitial shadows did not improve. Respiratory failure progressed, and 14 months after treatment initiation, bronchoscopy revealed turbid alveolar lavage fluid, numerous foamy macrophages, and numerous periodic acid-Schiff-positive unstructured materials. Blood test results revealed high anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody levels, leading to a diagnosis of APAP. The patient underwent whole-lung lavage, and the respiratory disturbance promptly improved. Anti-GM-CSF antibodies were measured from the cryopreserved serum samples collected at the time of diagnosis of anti-MDA5 antibody-positive dermatitis, and 10 months later, both values were significantly higher than normal. CONCLUSIONS: This is the first report of anti-MDA5 antibody-positive dermatomyositis complicated by interstitial pneumonia with APAP, which may develop during immunosuppressive therapy and be misdiagnosed as a re-exacerbation of interstitial pneumonia. In anti-MDA5 antibody-positive dermatomyositis, APAP comorbidity may have been overlooked, and early evaluation with bronchoalveolar lavage fluid and anti-GM-CSF antibody measurements should be considered, keeping the development of APAP in mind.

Knowledge of nursing staff before and after training on incontinence-associated dermatitis.

OBJECTIVE: To verify the knowledge of nursing staff before and after training on incontinence-associated dermatitis. METHOD: A study before and after an educational intervention carried out with nursing staff from the medical and surgical clinics and intensive care unit of the university hospital in June 2023. The training took place over three meetings. Data was collected using a questionnaire administered immediately before and after the training. McNemar's test for dependent samples was used to compare before and after training. RESULTS: 25 nurses and 14 nursing technicians took part. The items that showed statistical significance were related to the identification and correct differentiation of dermatitis associated with incontinence and pressure injury; and the correct way to sanitize the skin. CONCLUSION: The training of the nursing team made it possible to assess their knowledge of how to identify, prevent and treat incontinence-associated dermatitis.

An Update on Current Clinical Management and Emerging Treatments in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a severe, debilitating, chronic inflammatory skin disease characterized by recurrent painful nodules, abscesses and draining sinus tracts in intertriginous areas. While this condition appears to stem from follicular unit dysfunction, its cause is multifactorial and the exact pathogenesis has yet to be fully elucidated. These factors make treatment selection challenging and contribute to variable therapeutic response among affected patients. Typical regimens consist of a combination of medical and surgical modalities, tailored to individual responses. However, HS is often refractory to traditional treatments, prompting the need for newer and more effective therapies. Herein, we review current and emerging HS therapies.

Secoemestrin C Ameliorates Psoriasis-like Skin Inflammation in Mice by Suppressing the TNF-α/NF-κB Signaling Pathway.

OBJECTIVE: Secoemestrin C (SC), an epitetrathiodioxopiperazine isolated from Aspergillus nidulans, has been previously reported to have immunomodulatory and hepatoprotective effects against acute autoimmune hepatitis. However, the effect of SC on regulating the inflammation and its underlying mechanisms in the pathogenesis of psoriasis remain unclear. This study aimed to evaluate the effects of SC on inflammatory dermatosis both in vitro and in vivo. METHODS: In vitro, HaCaT cells were induced with tumor necrosis factor-alpha (TNF-α, 10 ng/mL) to establish an inflammatory injury model, and the expression of nuclear transcription factor-κB (NF-κB) pathway components was measured using qRT-PCR and Western blotting. An in vivo mouse model of imiquimod (IMQ)-induced psoriasis-like skin inflammation was used to evaluate the effectiveness of SC in alleviating psoriasis. RESULTS: SC significantly blocked the activation of NF-κB signaling in TNF-α-stimulated HaCaT cells. In addition, systemic and local administration of SC improved psoriatic dermatitis in the IMQ-induced mouse model. SC reduced skin scale and significantly inhibited the secretion of inflammatory factors in skin lesions. CONCLUSION: The protective effect of SC against psoriatic-associated inflammation reveals its potential therapeutic value for treating psoriasis.

Sweet Syndrome and Neutrophilic Dermatosis of the Dorsal Hands.

Sweet syndrome is a rare cutaneous condition with a broad clinical differential diagnosis. It can be classified into 3 subtypes: classic, malignancy-associated, and drug-induced. There are numerous associated disorders and provoking medications. Uncommonly, it can present as a multiorgan disease and cause significant morbidity. Systemic corticosteroids are the gold standard of treatment and yield rapid improvements in both lesions and symptoms. Nonsteroidal therapies may be effective alternatives, although high-quality comparative data are lacking. Some treatments for Sweet syndrome have paradoxically been implicated in the induction of disease.

Palisaded Neutrophilic Granulomatous Dermatitis, Bowel-Associated Dermatosis-Arthritis Syndrome, and Rheumatoid Neutrophilic Dermatitis.

Neutrophilic dermatosis is a heterogeneous group of inflammatory skin diseases characterized by the presence of a sterile neutrophilic infiltrate on histopathology. Three specific types of neutrophilic dermatoses are reviewed in this article: palisaded neutrophilic granulomatous dermatitis, bowel-associated dermatosis-arthritis syndrome, and rheumatoid neutrophilic dermatitis. The authors review the literature and highlight the clinical and histopathological features, disease pathogenesis, and the association of these conditions with various systemic diseases such as rheumatoid arthritis, inflammatory bowel disease, and others. A multidisciplinary approach is necessary for the diagnosis and management of these inflammatory skin conditions.

Association of different cell types and inflammation in early acne vulgaris.

Acne vulgaris, one of the most common skin diseases, is a chronic cutaneous inflammation of the upper pilosebaceous unit (PSU) with complex pathogenesis. Inflammation plays a central role in the pathogenesis of acne vulgaris. During the inflammatory process, the innate and adaptive immune systems are coordinately activated to induce immune responses. Understanding the infiltration and cytokine secretion of differential cells in acne lesions, especially in the early stages of inflammation, will provide an insight into the pathogenesis of acne. The purpose of this review is to synthesize the association of different cell types with inflammation in early acne vulgaris and provide a comprehensive understanding of skin inflammation and immune responses.

Clinical characteristics of the well-defined upper eyelid vascular network pattern in patients with rosacea.

BACKGROUND: Rosacea is a chronic inflammatory skin disease. The diagnosis is based on the symptoms and physical signs, which still lacks objective laboratory tests or imaging tests. OBJECTIVES: To propose and evaluate the upper eyelid network pattern in rosacea. METHODS: Participants included patients diagnosed with rosacea, other facial erythematous skin diseases, and normal controls, all of whom underwent full-face imaging utilizing the VISIA® system software. According to these images, researchers evaluated the condition of the upper eyelid vascular network, developed the grading scale and then compared the difference of distribution in the three groups. RESULTS: The occurrence rate of upper eyelid vascular network in rosacea was significantly higher than that in other facial erythematous skin diseases (84.3 vs. 32.0%, P < 0.001) and normal controls (84.3 vs. 28.0%, P < 0.001). The upper eyelid vascular network pattern was proposed (none [no clearly reticular vessels], mild [10-50% area of reticular vessels], moderate-to-severe [>50% area of reticular vessels]). Moderate-to-severe grade was defined as well-defined upper eyelid vascular network pattern, which was specific to patients with rosacea (rosacea vs. other facial erythematous skin diseases, adjusted odds ratio [aOR] = 5.814, 95% confidence interval [CI]: 3.899-8.670) (rosacea vs. heathy controls, aOR = 12.628, 95% CI: 8.334-19.112). The severity of the well-defined pattern had no significant association with age, duration, and phenotypes of rosacea (P > 0.05). CONCLUSION: The well-defined upper eyelid vascular network pattern specifically appeared in patients with rosacea, which could be a possible clue to the diagnosis of rosacea.

Post-inflammatory hyperpigmentation: A systematic review of treatment outcomes.

Post-inflammatory hyperpigmentation is a common consequence of inflammatory dermatoses. It is more common in patients with darker skin and has significant morbidity. This systematic review summarizes treatment outcomes for post-inflammatory hyperpigmentation to help physicians better predict clinical response and improve patient outcomes. Embase, MEDLINE, PubMed databases and clinicaltrials.gov were searched in accordance with PRISMA guidelines using a combination of relevant search terms. Title, abstract and full text screening were done in duplicate. Studies were included if they met our predetermined PICOS framework criteria. Results are presented in descriptive form. In total, 41 studies representing 877 patients were included. Complete response was achieved by laser and energy-based devices in 18.1% (n = 56/309) of patients, topicals in 5.4% (n = 20/369) and combination therapies in 2.4% (n = 4/166). Partial response was achieved by combination modalities in 84.9% (n = 141/166) of patients, topicals in 72.4% (n = 267/369), laser and energy-based devices in 61.2% (n = 189/309) and peels in 33.3% (n = 5/15). Poor to no response occurred with peels in 66.7% (n = 10/15) of patients, topicals in 22.2% (n = 82/369), laser and energy-based devices in 18.1% (n = 56/309) and combination modalities in 12.7% (n = 21/166). Additionally, in 2.6% (n = 8/309) of patients treated with laser and energy-based devices, post-inflammatory hyperpigmentation worsened. Adverse events were reported in 10 patients, all while using topical treatments. In conclusion, the current treatment approaches yielded unsatisfactory rates of complete response. However, combination therapies, laser and energy-based devices and topical therapies showed high rates of partial response. Of note, the majority of post-inflammatory hyperpigmentation cases included were associated with acne, and therefore, the findings and conclusions drawn may have limited applicability to other types of post-inflammatory hyperpigmentation.

What's New in Cutaneous T-Cell Lymphoma-Associated Pruritus.

Cutaneous T-cell lymphomas are a heterogenous group of lymphomas that cause various skin manifestations. Severe pruritus occurs frequently in cutaneous T-cell lymphoma and negatively impacts patients' quality of life. The pathophysiology of cutaneous T-cell lymphoma-associated itch is complex and involves various immune cells, inflammatory cytokines, and neuroimmune interactions. Treating cutaneous T-cell lymphoma pruritus can be challenging, and there have been few randomized controlled studies evaluating the use of antipruritic treatments in these patients. Systemic therapies targeting the disease have also been shown to have some antipruritic effects. Furthermore, although biologic therapy has revolutionized the treatment of other pruritic skin conditions, the use of biologics in cutaneous T-cell lymphoma remains controversial.

[Two cases of anti-nuclear matrix protein 2 antibody-positive dermatomyositis sine dermatitis with severe diffuse subcutaneous edema and dysphagia].

Case 1 involved a 68-year-old woman who was admitted to our hospital because of muscle weakness, diffuse subcutaneous edema, dysphagia, and an elevated serum creatine kinase level that had worsened within the previous month. Case 2 involved a 78-year-old woman who was admitted to our hospital because of muscle weakness, bilateral shoulder pain, diffuse subcutaneous edema, and dysphagia that had gradually worsened during the past 5 months. Both patients showed severe diffuse subcutaneous edema and dysphagia and underwent enteral tube feeding. Although they had no skin lesions consistent with dermatomyositis, muscle biopsies showed myxovirus resistance protein A (MxA) expansion, and blood tests showed positivity for anti-nuclear matrix protein 2 (anti-NXP-2) antibody. Therefore, both presents were diagnosed with anti-NXP-2 antibody-positive dermatomyositis sine dermatitis (DMSD). Anti-NXP-2 antibody-positive dermatomyositis has been reported to be closely associated with DMSD, severe edema and dysphagia. Differential diagnosis for patients who develop myositis with severe subcutaneous edema and dysphagia should include anti-NXP-2 antibody-positive dermatomyositis, and it is important to consider measurement of anti-NXP-2 antibody.

Radiobiological modelling of radiation-induced acute skin toxicity (dermatitis): A single institutional study of breast carcinoma.

Purpose: The purpose of the study was to estimate the fitting parameters of the sigmoidal dose response (SDR) curve of radiation-induced acute dermatitis in breast cancer patients treated with intensity-modulated radiation therapy for calculation of normal tissue complication probability (NTCP). Materials and Methods: Twenty-five breast cancer patients were enrolled to model the SDR curve for acute dermatitis. The acute radiation-induced (ARI) dermatitis toxicity was assessed weekly for all the patients, and their scores were determined using the common terminology criterion adverse events version 5.0. The radiobiological parameters n, m, TD50, and γ50 were derived using the fitted SDR curve obtained from breast cancer Patient's clinical data. Results: ARI dermatitis toxicity in carcinoma of breast patients was calculated for the end point of acute dermatitis. The n, m, TD50, and γ50 parameters from the SDR curve of Grade-1 dermatitis are found to be 0.03, 0.04, 28.65 ± 1.43 (confidence interval [CI] 95%) and 1.02 and for Grade-2 dermatitis are found to be 0.026, 0.028, 38.65 ± 1.93 (CI. 95%) and 1.01 respectively. Conclusion: This research presents the fitting parameters for NTCP calculation of Grade-1 and Grade-2 acute radiation-induced skin toxicity in breast cancer for the dermatitis end point. The presented nomograms of volume versus complication probability and dose versus complication probability assist radiation oncologists in establishing the limiting dose to reduce acute toxicities for different grades of acute dermatitis in breast cancer patients.

Outbreaks of dermatopathy caused by Tephrosia noctiflora intoxication in Brazilian cattle.

This study aims to update the knowledge concerning the intoxication by Tephrosia noctiflora in Brazilian cattle herds by reporting new cases of intoxication in lactating cows, their calves and bulls and highlight the epidemiology, clinical signs, pathogenesis, gross, and microscopic lesions. The morbidity and mortality of this intoxication in the farms studied was low. Gross lesions in all affected cattle consisted of dermatitis with hyperpigmentation, crusts, ulceration, erythema, and lichenification in the skin of limbs, ventral abdomen, perianal and perineal areas of lactating calves and adult cattle. Microscopically, the main lesion observed consisted of severe dermatitis with parakeratotic hyperkeratosis, papillated proliferation, and diffuse, accentuated lymphoplasmacytic inflammatory infiltrate in the epidermis and dermis. The presence of skin lesions mainly in the limbs and ventral abdomen of cattle implies the pathogenesis of intoxication is related to a primary contact dermatitis, and the occurrence of similar lesions on the skin of nursing calves reinforces this hypothesis. The putative toxins of T. noctiflora have been thought to be rotenoids. Additional work is needed to define better if these compounds are the main toxin responsible for the dermatopathy observed in these herds.

Revisiting the interleukin 17 family of cytokines in psoriasis: pathogenesis and potential targets for innovative therapies.

Psoriasis is a common chronic inflammatory skin disease, associated with substantial comorbidity. TH17 lymphocytes, differentiating under the influence of dendritic cell-derived IL-23, and mediating their effects via IL-17A, are believed to be central effector cells in psoriasis. This concept is underlined by the unprecedented efficacy of therapeutics targeting this pathogenetic axis. In recent years, numerous observations made it necessary to revisit and refine this simple "linear" pathogenetic model. It became evident that IL-23 independent cells exist that produce IL-17A, that IL-17 homologues may exhibit synergistic biological effects, and that the blockade of IL-17A alone is clinically less effective compared to the inhibition of several IL-17 homologues. In this review, we will summarize the current knowledge around IL-17A and its five currently known homologues, namely IL-17B, IL-17C, IL-17D, IL-17E (also known as IL-25) and IL-17F, in relation to skin inflammation in general and psoriasis in particular. We will also re-visit the above-mentioned observations and integrate them into a more comprehensive pathogenetic model. This may help to appreciate current as well as developing anti-psoriatic therapies and to prioritize the selection of future drugs' mode(s) of action.

Bacterial species distribution on the genital skin of hospitalized patients with stroke manifesting incontinence-associated dermatitis: A cross-sectional study.

AIM: To compare the isolated and identified bacterial species colonizing on the genital skin between patients with and without incontinence-associated dermatitis. METHODS: This cross-sectional study included 102 patients with stroke admitted to an acute hospital in Japan. Swabs were collected, and bacterial species found in swabs were isolated and identified using a selective agar medium and simple identification kits. In addition to demographic information, severity of incontinence-associated dermatitis and the total bacterial counts were measured. RESULTS: Incontinence-associated dermatitis was present in 53.9% of the participants. Staphylococcus aureus was found in 50% of the participants with incontinence-associated dermatitis and only 17.9% of those without incontinence-associated dermatitis (P = 0.0029). Bacterial species distribution by erythema and skin erosion, which denote severity of incontinence-associated dermatitis, was different, but not significant; additionally, the total number of bacterial colonies was equivalent. CONCLUSIONS: Bacterial species distribution differed between patients with and without incontinence-associated dermatitis, whereas the total number of bacterial colonies was equivalent. A high detection rate of S. aureus on genital skin sites potentially affects the presence of incontinence-associated dermatitis and its severity. Geriatr Gerontol Int 2023; 23: 537-542.

Microblading-Induced Granulomatous Reaction: Case Report and Review of the Literature.

ABSTRACT: Microblading is a common cosmetic procedure that can modify the appearance of one's eyebrows. Although generally well-tolerated, the procedure can cause a number of dermatologic issues; on rare occasions, granulomatous reactions can manifest. We use this case to highlight a presentation of a nonsarcoidal granulomatous dermatitis and review the literature on granulomatous reactions secondary to microblading. Of the 21 cases included in our review, approximately half (10/21) were diagnosed with foreign-body granulomas and the other half with sarcoidosis (7 of 21 with systemic sarcoidosis and 4 of 21 with cutaneous sarcoidosis). Although microblading remains a commonplace cosmetic technique, it is not without risk. Much like other types of tattoos, microblading can cause granulomatous reactions for which we must be vigilant, and further workup for sarcoidosis might be considered in select patients.

Inborn Errors of Immunity in Hidradenitis Suppurativa Pathogenesis and Disease Burden.

Hidradenitis suppurativa (HS), also known as Verneuil's disease and acne inversa, is a prevalent, debilitating, and understudied inflammatory skin disease. It is marked by repeated bouts of pathological inflammation causing pain, hyperplasia, aberrant healing, and fibrosis. HS is difficult to manage and has many unmet medical needs. There is clinical and pharmacological evidence for extensive etiological heterogeneity with HS, suggesting that this clinical diagnosis is capturing a spectrum of disease entities. Human genetic studies provide robust insight into disease pathogenesis. They also can be used to resolve etiological heterogeneity and to identify drug targets. However, HS has not been extensively investigated with well-powered genetic studies. Here, we review what is known about its genetic architecture. We identify overlap in molecular, cellular, and clinical features between HS and inborn errors of immunity (IEI). This evidence indicates that HS may be an underrecognized component of IEI and suggests that undiagnosed IEI are present in HS cohorts. Inborn errors of immunity represent a salient opportunity for rapidly resolving the immunological landscape of HS pathogenesis, for prioritizing drug repurposing studies, and for improving the clinical management of HS.

A case of palisaded neutrophilic and granulomatous dermatitis associated with systemic lupus erythematosus presenting with pustules.

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a relatively rare skin disease that is characterized by a reactive granulomatous histopathological pattern and is often associated with systemic autoimmune diseases. We encountered a case of PNGD that presented with pustules, although the prototypical clinical presentation of PNGD is mainly erythema and papules. Here, this rare case of PNGD with pustules is presented and discussed in relation to the relevant literature.

Clinical tolerance of untreated reflux after iliac vein stent placement.

BACKGROUND: We have recently demonstrated in a large patient cohort that the prevalence and severity of reflux will improve in most limbs after stenting and that most limbs will not develop new-onset reflux. In the present report, we have focused on the long-term clinical outcomes associated with untreated reflux in the same patient cohort who had undergone iliofemoral venous stenting without correction of residual reflux. METHODS: The clinical outcomes data from 1379 limbs treated with only iliac vein stenting without correction of superficial or deep reflux from 1997 to 2018 were analyzed (23-year follow-up period). Of the 1379 limbs, 632 (46%) had had preexisting reflux before stenting and 747 (54%) had did not. The reflux data (reflux segmental score, air plethysmography, ambulatory venous pressure) for these patients have been previously reported in detail. The subsets were compared perioperatively with each other using the following variables: grade of swelling, visual analog scale for pain score, venous clinical severity score, venous stasis dermatitis, ulceration, and quality of life measures. RESULTS: Both groups demonstrated improvements in the venous clinical severity score, grade of swelling, visual analog scale score, and quality of life. No differences were found in ulcer healing (5% vs 3% for limbs with and without prestent reflux, respectively) and resolution of dermatitis (6% vs 5% for limbs with and without prestent reflux, respectively) between the two groups. Of the 632 limbs with preexisting reflux, 218 (34%) had had axial reflux and 414 had had nonaxial reflux (66%). The clinical outcomes were similar between the two groups. Using a multisegment reflux score, the limbs with prestent reflux (n = 632) were divided into two groups. A segmental score of ≥3 indicated severe reflux and a score of <3 indicated moderate reflux. Of these 632 limbs, 161 (25%) had severe reflux and 471 (75%) had moderate reflux. The two groups demonstrated similar outcomes for most clinical parameters. The post-thrombotic limbs and nonthrombotic limbs also showed similar outcomes. CONCLUSIONS: The long-term follow-up of patients after iliac vein stenting showed that uncorrected reflux is well tolerated by most patients across most clinical measures.

Neutrophilic dermatosis of the dorsal hands: A review of 123 cases.

Neutrophilic dermatosis of the dorsal hands (NDDH) is an uncommon localized variant of Sweet syndrome first described in 1995. It is characterized by tender erythematous plaques, pustules, and bullae on the dorsa of the hands. A total of 123 cases of NDDH are included in this review. The mean patient age was 62.1 years, and there was a slight female preponderance. Overall, 78.0% of cases had bilateral involvement, and other sites were affected in almost a third of cases. Underlying disease was found in ∼40% of patients, with the most common associations being hematologic disorders (gammopathies, myelodysplasias, or malignancies), recent infection, solid organ tumors, and inflammatory bowel disease. Systemic or topical corticosteroids or both were employed in the treatment of 88.1% of cases, while dapsone, colchicine, and tetracyclines were the most common steroid-sparing agents used. Improvement was often rapid and complete resolution the norm. Although uncommon, NDDH is frequently misdiagnosed, and thus, its exact prevalence is probably underestimated. Misdiagnosis might have significant implications, including treatment delays or incorrect management. Moreover, recognition of NDDH is important, since a correct diagnosis should trigger a search for underlying diseases and proper treatment with corticosteroids, steroid-sparing agents, or both, which is almost invariably curative.