搜索结果：Case reports in dermatology

Introduction Relapsing polychondritis (RP) is an uncommon disease that may be associated with other rheumatologic or autoimmune conditions (30%–35%) and with myelodysplasia (5%–10%) (24,28,34). RP is characterized by recurrent inflammation and degeneration of cartilaginous tissue, especially auricular, nasal, and laryngeal/tracheal cartilages. In fact, many other tissues may be involved, such as the eye, heart, blood vessels, and inner ear (23,25,32,34). Dermatologic manifestations have been relatively poorly studied compared to other signs. In previous studies (23,34), a significant number of patients with RP were reported to have leukocytoclastic vasculitis. We conducted the present study to analyze the dermatologic manifestations of 200 patients with RP. Patients and Methods Between 1974 and 2000, 200 patients with RP were followed in our university referral center for connective tissue disorders as in-or outpatients. To qualify for the study, patients had to fulfill the diagnostic criteria defined by Michet et al (25). Indeed, all had a documented history of inflammatory episodes, involving at least 2 of 3 sites (auricular, nasal, laryngotracheal cartilages) or 1 of these sites together with 2 other manifestations, including ocular inflammation (conjunctivitis, keratitis, episcleritis, uveitis), hearing loss, vestibular dysfunction, or seronegative inflammatory arthritis (25). Histologic proof of cartilage involvement was not required for inclusion. The patients, 129 women and 71 men, had a mean age of 43 ± 18 years (range, 6–87 yr) at the time of the first chondritis. Patients were seen by 1 of us (JCP) and the presence of cutaneous or mucosal lesions was systematically checked. All those who displayed dermatologic involvement were examined at least once by an experienced dermatologist (CF) who recorded all previous and current dermatologic manifestations. Clinical and laboratory data were analyzed retrospectively. Oral aphthosis was diagnosed when recurrences occurred at least 3 times during a 12-month period according to O’Duffy criteria for aphthae in Behçet disease (22). Genital aphthae were always noted regardless of the number of recurrences (18). Complex aphthosis is defined as the association of oral and genital aphthoses. Raynaud phenomenon and frequent infectious skin lesions, such as herpes infections, were not taken into account. Associated diseases were diagnosed using standard criteria. Patients with an associated disease with possible dermatologic involvement or chronic dermatitis were analyzed separately; the clinical and laboratory data for the remaining patients, with or without dermatologic manifestations, were compared. Myelodysplasia was diagnosed in patients with chronic macrocytic refractory anemia (hemoglobin < 10 g/dL) not explained by vitamin or hormone deficiency or renal failure. Age at the time of the first chondritis, sex ratio, and frequency of dermatologic manifestations were compared between patients without associated disorders and those with myelodysplastic syndrome. A total of 82 skin or mucosal biopsy specimens available from 59 patients were examined by 1 of us (JLL) who had no knowledge of the clinical data. All specimens were stained with hematoxylin-eosin-saffron. Direct immunofluorescence was performed on 17 skin biopsy specimens clinically suggestive of vasculitis. Statistical comparisons were made using the chi-square test for qualitative data and the Wilcoxon test for quantitative data. Values of p less than 0.05 were considered significant. Results Seventy-three (27 male/46 female patients) of the 200 patients with RP had at least 1 associated disease with potential dermatologic involvement or chronic dermatitis (Table 1). The other 127 patients (44 male/83 female) had a mean age of 41.4 ± 17 years (range, 5–84 yr) at the time of the first chondritis. Forty-five (35.4%) of them had dermatologic manifestations (Table 2), which were the first manifestations of RP in 15 (12%) cases. The dermatologic manifestations preceded the first chondritis in 20 (15.7%) cases by 10 days to 20 years (mean, 45.6 ± 64 mo), appeared concomitantly with the first chondritis in 11 (8.6%) cases, and appeared secondarily in 14 (11%) cases with a mean time lapse from the first chondritis of 59 ± 56 months (range, 1–172 mo). They occurred concomitantly with chondritis attacks in 23 cases and independently in 22 cases. Oral aphthosis was the most common manifestation, present in 21 patients, 7 of whom also had genital involvement. No patient had genital without oral aphthae. Nodules on the limbs frequently appeared as erythema nodosum-like lesions. However, the histologic findings in these lesions were diverse since septal panniculitis was observed in only 3 of 8 biopsy specimens. Other histologic findings included thrombosis or vasculitis of skin vessels and deep dermal neutrophil infiltrates resembling those seen in some deep lesions of Sweet syndrome. Purpura corresponded to leukocytoclastic or, rarely, lymphocytic vasculitis. Papules were either urticarial corresponding to leukocytoclastic or lymphocytic vasculitis, or bluish-red corresponding to Sweet syndrome or leukocytoclastic vasculitis. Superficial phlebitis was confirmed by venous echoDöppler without biopsy. Skin ulcerations were observed predominantly on the limbs and were secondary to small-vessel vasculitis or thrombosis. In 1 case, the ulceration had the clinical and histologic features of pyoderma gangrenosum. Taken altogether regardless of the clinical features, histologic findings showed leukocytoclastic vasculitis (n = 17), lymphocytic vasculitis (n = 2), neutrophil infiltrates (n = 6), thrombosis of skin vessels (n = 4), septal panniculitis (n = 3), or minor changes (n = 2). Direct immunofluorescence performed on skin biopsy specimens with leukocytoclastic vasculitis (n = 9) was either negative (n = 5) or positive with vascular deposits of C3 (n = 4), IgG (n = 2), and/or IgM (n = 2). No clear preferential association was observed among the various clinical dermatologic lesions (Table 3). Patients with and without dermatologic manifestations did not differ with regard to male/female ratio (15/30 versus 29/53); age at RP onset (40.5 ± 18 yr versus 42 ± 17 yr); prevalence of auricular (93% versus 76%), nasal (71% versus 71%), or laryngotracheobronchial chondritis (62% versus 55%); and prevalence of articular (96% versus 79%), ocular (78% versus 60%), audiovestibular (51% versus 41%), large artery (26% versus 12%), or deep venous (6% versus 2%) involvement.TABLE 1: Associated diseases in 73 patients with relapsing polychondritisTABLE 2: Dermatologic manifestations and histologic findings in 45 of 127 patients with relapsing polychondritis without associated diseaseTABLE 3: Number of patients with associated dermatologic manifestations among the 45 patients without associated diseaseTwenty-two patients had myelodysplasia; some of these patients were reported briefly previously (26). One had dermatomyositis diagnosed 2 years before RP without other dermatologic lesions. In another patient, Crohn disease was diagnosed 1 month after RP. The dermatologic manifestations observed in 20 of these 22 patients and their corresponding clinicopathologic findings are listed in Table 4. Eight patients presented with dermatologic manifestations 10.3 ± 10 months (range, 0.5–24 mo) before the first chondritis episode. Dermatologic manifestations developed concomitantly with the first chondritis in 5 cases and secondarily in 7 (mean time lapse, 56 ± 20 mo; range, 3–153 mo). They occurred simultaneously with chondritis attacks in 12 cases and independently in 8 cases. One of the 2 patients with IgA myeloma had urticarial vasculitis with IgA skin vessel deposits. Direct immunofluorescence performed on skin biopsy specimens from patients with myelodysplastic syndrome with leukocytoclastic vasculitis (n = 7) was either negative (n = 3) or positive with vascular deposits of C3 (n = 4), IgG (n = 1), and/or IgM (n = 1).TABLE 4: Dermatologic manifestations and histologic findings in 22 patients with relapsing polychondritis and myelodysplastic syndromeDermatologic manifestations that may be related to RP in patients with other diseases are reported in Table 5. Among patients with systemic lupus erythematosus, 4 had acute cutaneous lupus erythematosus, 2 had subacute cutaneous lupus erythematosus, and 1 had discoid lupus erythematosus. All patients with mixed connective tissue disease had acrosclerosis. Cutaneous lesions of dermatomyositis were obvious in patients with this diagnosis.TABLE 5: Dermatologic manifestations that may be related to relapsing polychondritis in 51 patients with relapsing polychondritis and other diseases (except myelodysplastic syndrome)*Eight patients had autoimmune thyroid diseases. One of them also had myelodysplasia with several dermatologic manifestations: livedo reticularis, nodules, sterile pustules, nonurticarial papules, superficial phlebitis, and distal necrosis. Four skin biopsy specimens of different lesions showed dermal neutrophil infiltrates, leukocytoclastic vasculitis, lymphocytic vasculitis, or deep vessel thromboses. Among the other 7 patients, 3 had dermatologic manifestations: purpura (n = 2), nodules (n = 1), superficial phlebitis (n = 1), and limb ulcerations (n = 1). Nine patients had associated chronic dermatitis. One also had dermatomyositis, and another had aseptic visceral abscesses. In only 1 of the 2 patients with lichen planus, erythema nodosum-like lesions of the legs could be associated with RP and occurred concomitantly with attacks. Both patients with histologically proven Crohn disease presented with dermatologic manifestations, which could be attributed to either Crohn disease or RP. One patient had oral aphthosis; the other had purpura, urticarial vasculitis, and superficial phlebitis in association with myelodysplasia. The 4 patients with deep aseptic abscesses had dermatologic manifestations, including erythema nodosum-like lesions (n = 3), aphthosis (complex: n = 1; oral: n = 1), and aseptic skin abscesses with subsequent ulceration (n = 2). The frequency of dermatologic manifestations (91% versus 35.4%; p < 0.0001), sex ratio (18 male/4 female versus 44 male/83 female; p < 0.0001), and age at the time of the first chondritis (63.3 ± 14 yr versus 41.4 ± 17 yr; p < 0.0002) were significantly higher in the 22 patients with myelodysplasia than in the 127 patients without any associated disease. Discussion Dermatologic manifestations have been reported frequently in various series of patients with RP, but without details of the clinical features and corresponding pathologic findings. The frequency of skin lesions ranged from 17% to 36% in the largest series reported in the literature (23,25,32,34), but adjacent mucosal involvement was not specified. In contrast, dermatologic manifestations have been described accurately in isolated case reports (4,8,30). The lack of specificity of the observed dermatologic manifestations and the high frequency of associated diseases potentially featuring similar skin or mucosal involvement complicated the analysis of dermatologic manifestations in this series. All patients with such overlapping disorders, with the exception of Sjögren syndrome which was not systematically searched for, were analyzed separately. This approach meant that a minimum frequency of dermatologic manifestations, that is, 35.5% in the group of 127 patients with “pure” RP, was reported. Indeed, the frequency of dermatologic manifestations was extremely high in some groups of patients, especially those with RP-associated myelodysplasia or Crohn disease (91% and 2 of 2, respectively), confirming our preliminary report (28). These frequencies were much higher than those usually observed when these disorders are not associated with RP, suggesting that RP plays its own role in their occurrence. Cutaneous involvement in unselected patients with myelodysplasia can take the form of either a malignant infiltration or various benign lesions. Both types of lesions were observed in 14 (7.8%) patients in a recent series of 180 patients, with the latter present in 12 (2). Besides the cutaneous infections common in neutropenic patients, benign lesions included cutaneous vasculitis and various neutrophilic dermatoses (2). The frequency of dermatologic manifestations in patients with Crohn disease has been reported to be as high as 34%. These manifestations include granulomatous-specific lesions, reactive lesions, other miscellaneous disorders, and malnutrition-associated lesions (6,15). The most common reactive lesions are similar to those observed in RP, that is, aphthosis, neutrophilic dermatosis, vasculitis, and urticaria. Oral aphthosis was the most common dermatologic manifestation seen in our series. Aphthae in RP did not differ from those of simple recurrent aphthosis. Oral aphthae were associated with genital aphthae in 12 cases: 7 patients without associated disease (see Table 2), 2 patients with myelodysplastic syndrome (see Table 4), and 3 patients with other diseases (see Table 5). Complex aphthosis is not synonymous with Behçet disease; it has also been reported in patients with inflammatory bowel diseases (6) and chronic myeloid leukemia patients treated with interferon-alpha (5). Due to the lack of specificity of complex aphthosis, patients with oral and genital aphthae were not considered to have the association of Behçet disease and RP, termed “MAGIC syndrome” (Mouth And Genital ulcers with Inflamed Cartilage) by Firestein et al in 1985 (10). Indeed, patients with and without complex aphthosis did not differ with regard to other dermatologic (see Table 3) or systemic manifestations of RP. For example, ocular manifestations, present in 9 of 12 (75%) patients with complex aphthosis, were similar to those observed in RP (19) : scleritis (n = 5), conjunctivitis (n = 5), and/or keratitis (n = 3). One patient with associated spondylarthropathy had iridocyclitis. No patients suffered from retinal vasculitis, posterior uveitis, or anterior uveitis with hypopyon, which are common in patients with Behçet disease (3). Nodules on the limbs were the most common skin lesions; they have been described frequently as erythema nodosum-like lesions (30). Indeed, septal panniculitis was noted in many cases. However, other pathologic findings were also observed, such as thrombosis, vasculitis (29), and deep neutrophil infiltrates. Nodules corresponding to the latter were always associated with other neutrophilic dermatoses (see Tables 2, 4), such as Sweet syndrome (7 cases), pyoderma gangrenosum (1 case), and erythema elevatum diutinum (2 cases). These neutrophilic dermatoses may occur as diseases confined to the skin (idiopathic), but they also may be associated with hematologic disorders and arthritis. All these diverse neutrophilic dermatoses have been reported previously in isolated cases of patients with RP (19,21). Sweet syndrome-like lesions and pyoderma gangrenosum may be associated also with inflammatory bowel diseases (6) or Behçet disease (14). Pyoderma gangrenosum-like lesions have been observed also in patients with systemic vasculitis, such as Wegener granulomatosis or Takayasu arteritis (11,12). Four of our patients with RP had deep splenic or mesenteric abscesses associated with various dermatologic manifestations, that is, pseudofolliculitis, cutaneous abscesses, aphthosis, erythema nodosum-like lesions; they preceded the onset of chondritis, which provided the diagnosis of RP. In these patients, no inflammatory bowel disease was detected by endoscopy, unlike the majority of patients with aseptic visceral abscesses reported in our group (1). Palpable purpuric and urticarial lesions corresponding to leukocytoclastic vasculitis or necrotizing venulitis may be drug-induced or encountered in many diseases, such as infections, connective tissue diseases, systemic vasculitis, inflammatory bowel diseases, and hematologic and other malignant disorders. Only 1 patient with IgA myeloma had IgA skin vessel deposits excluding in others the diagnosis of IgA-mediated vasculitis. No correlation was found between skin vasculitis and the presence of antineutrophil cytoplasm antibodies previously detected in 24% of RP patients (26). The importance of vasculitis in the pathogenesis of RP has been emphasized by several authors, especially with regard to its dermatologic manifestations (17,23,24). Our data confirm that a vasculitic process is indeed frequently present, but other aspects also may be discovered by histologic examination. Among them, thrombosis of skin vessels was observed in 4 patients without associated disorders and in 3 patients with myelodysplasia. The mechanism of thrombosis remains unclear. These patients did not have antiphospholipid antibodies (lupus anticoagulant or anticardiolipin antibodies), monoclonal cryoglobulin, or cryofibrinogen. Extensive investigations to detect other thrombophilic abnormalities were not performed in the oldest cases. Antiphospholipid antibodies were mostly detected when RP overlapped with another disorder, such as systemic lupus erythematosus in women and myelodysplasia in older men (27). The lack of specificity of the diverse dermatologic manifestations frequently encountered in patients with RP explains why these manifestations were not included in the diagnostic criteria proposed by Michet et al in 1986 (25). Nonetheless, their development coincided with chondritis in half the cases. Furthermore, they may be observed without any associated disorder and therefore are probably directly related to RP. Other dermatologic manifestations, such as psoriasis (7,9,16), Reiter syndrome (31), lichen planus, alopecia areata (20), or vitiligo, probably result from associated immune disturbances. In conclusion, dermatologic manifestations of RP are frequent, especially in association with myelodysplasia. They are nonspecific, similar to those observed in Behçet and inflammatory bowel diseases. Their presence in the elderly warrants repeated blood cell counts to detect a smouldering myelodysplasia. Summary Dermatologic manifestations of relapsing polychondritis (RP) have been relatively poorly studied compared to other manifestations. In this study we describe dermatologic manifestations in a large series of patients with RP and the corresponding pathologic findings. In this retrospective, single-center review of 200 patients diagnosed with RP according to Michet’s criteria, we analyzed separately those suffering from associated diseases with potential dermatologic involvement or chronic dermatitis. Skin or mucosal biopsies taken from 59 patients were examined without knowledge of the clinical data. Among the 200 patients with RP, 73 had chronic dermatitis or associated diseases with potential dermatologic involvement, especially hematologic disorders (n = 24) and connective tissue diseases (n = 22). Among the other 127 patients, 45 (35.4%) had dermatologic manifestations: aphthosis (n = 21; oral in 14 and complex in 7), nodules on the limbs (n = 19), purpura (n = 13), papules (n = 10), sterile pustules (n = 9), superficial phlebitis (n = 8), livedo reticularis (n = 7), ulcerations on the limbs (n = 6), and distal necrosis (n = 4). Dermatologic manifestations were the presenting feature of RP in 15 cases (12%), and appeared concomitantly (n = 23) or not (n = 22) with attacks of chondritis. Histologic findings included vasculitis (n = 19, leukocytoclastic in 17 and lymphocytic in 2), neutrophil infiltrates (n = 6), thrombosis of skin vessels (n = 4), septal panniculitis (n = 3), and minor changes (n = 2). Patients with and without dermatologic manifestations did not differ with regard to male/female ratio; age at RP onset; frequency of auricular, nasal, or tracheobronchial chondritis; or frequency of rheumatologic, ocular, audiovestibular, renal, arterial, or venous involvement. The frequency of dermatologic manifestations (91% versus 35.4%; p < 0.0001), sex ratio (18 male/4 female versus 44 male/83 female, p < 0.0001), and age at first chondritis (63.3 ± 14 yr versus 41.4 ± 17 yr; p < 0.0002) were significantly higher in the 22 patients with myelodysplastic syndrome than in the 127 patients without any associated disease. In conclusion, although dermatologic manifestations occur frequently in patients with RP, especially in association with myelodysplasia, they are nonspecific and sometimes resemble those observed in Behçet disease or inflammatory bowel diseases. Their presence in the elderly warrants repeated blood cell counts to detect a smouldering myelodysplasia.

Levamisole is a veterinary anthelmintic drug with immunomodulatory properties in humans. It has become increasingly common as a contaminant in cocaine and is now detected in the majority of cocaine seized in the United States. A variety of adverse reactions have been reported in association with levamisole, the most severe being agranulocytosis, vascular occlusive disease, and thrombotic vasculopathy, with or without vasculitis. The combination of rapidly progressive cutaneous ecchymosis and purpura leading to necrosis, often affecting the ears and cheeks; neutropenia or agranulocytosis; serologic autoantibodies; and thrombotic vasculopathy, with or without associated vasculitis, in a patient who has recently used cocaine is characteristic of exposure to contaminant levamisole. We report the case of a 54-year-old man who presented with the clinical findings of levamisole-contaminated cocaine use and review the literature regarding cutaneous reactions associated with levamisole. Our case highlights this important public health issue and represents a clinical course that is unusually severe.

First described in 1878, vulvar hidradenoma papilliferum (HP) is a rare but benign adnexal tumor derived from mammary-like glands in the anogenital region.1 Among cutaneous lesions, adnexal tumors are rare, with incidence and prevalence data of these benign tumors lacking in comparison to that of malignant adnexal tumors.2, 3 Of the benign adnexal vulvar lesions, HP is the most common, accounting for approximately 60% of benign vulvar adnexal lesions and 40% of total vulvar adnexal lesions.1 Cases of HP have been reported in patients from 20 to 90 years of age, most commonly occurring in the fourth to fifth decade of life.1, 4 This aligns with the age pattern noted for other cutaneous adnexal lesions.2 All published cases of vulvar HP have occurred in postpubertal individuals, with some studies suggesting that reproductive hormones may play a role.4 The exact causal mechanism of this age predilection, however, is unknown. Most patients with vulvar HP are asymptomatic (>70%) and their lesions are described as slow-growing.4 When symptomatic, the most common symptoms reported are increasing size, pruritus, and bleeding.4 The location of these lesions mirrors the distribution of anogenital mammary-like glands, most commonly occurring in the labia minora and majora, and less frequently affecting the fourchette and clitoris.4 Histologically, HP is analogous to intraductal papilloma arising in the breast showing glands and papillae, which are interconnected and anastomosing with an inner epithelial layer and outer myoepithelial layer.5 Epithelial metaplasia (oncocytic/apocrine or clear cell change), along with solid and cystic architecture, can also be seen. HP is a dermal-based lesion and typically lacks a connection to the overlying epidermis. A 48-year-old woman reported a 6-month history of a right vulvar lesion, initially described as pea-sized, nonpruritic, and nontender. No preceding trauma, irritation, or similar lesions in the past were noted. She was initially seen by her family physician who recommended sitz baths and topical analgesia while awaiting outpatient gynecologic consult with minimal improvement following the implementation of these conservative measures. An outpatient ultrasound was performed 3 months after the lesion was first appreciated, which described an 11 × 6 × 12-mm complex cyst with internal echoes. The margins were smooth and well circumscribed, with peripheral hyperemia noted. Differential diagnosis based on this ultrasound included an epidermal inclusion cyst or skin appendage lesion. The patient presented to the emergency department for assessment when the lesion became acutely painful and pruritic over a 2-week period. It was gradually enlarging and bled secondary to friction. On examination, there was a well-circumscribed, 15 × 15-mm erythematous nodular lesion at the 10-o'clock position of the right labia majora (Figure 1). No spontaneous drainage or frank bleeding was noted from the lesion; however, it was visibly friable and tender to palpation. Her review of symptoms was negative, and findings from physical examination were otherwise unremarkable. She was given a prescription for topical lidocaine, and a biopsy of the lesion was recommended. She subsequently underwent wide local excision of the right vulvar mass, under general anesthetic, with no postoperative complications. The surgical specimen was sent for histopathological examination, which revealed a diagnosis of HP (Figures 2 and 3). Despite being first described almost 150 years ago, vulvar HP remains a relatively unfamiliar diagnosis among healthcare providers. Multidecade studies have reported <100 cases,1 with the most recent reports documenting <10 cases.6 Vulvar HP lesions also display significant variation in their dermatological appearance, including color (red, nonpigmented, and blue lesions have been described), size (<10 mm up to 25 mm), and morphologies (nodules, plaques, ulcerations, and others).4, 6 As a result, clinically, there is often a broad differential diagnosis including but not limited to cystadenoma, adenofibroma, syringocystadenoma papilliferum, bartholin gland cyst/abscess, melanoma, adenocarcinoma, and squamous cell carcinoma.1, 2, 4, 6 The rarity, dermatological variation, and generally asymptomatic nature of vulvar HP contribute to its under recognition in healthcare settings. It is pertinent to obtain a histopathological diagnosis of vulvar HP to rule out a malignant neoplasm and assess margins.2 HP is benign but local recurrence may follow incomplete excision. Malignant transformation is exceptionally rare; malignant tumors analogous to malignant breast tumors, including carcinoma in situ resembling breast ductal carcinoma in situ and mammary-type carcinoma, have been reported.7, 8 As such, recommended management includes complete excision with margins and histopathological assessment.2 Case reports on vulvar HP expand our knowledge of this rare lesion and its diverse dermatological presentations. We encourage additional studies that demonstrate its heterogenous appearance, especially in Black, Indigenous, and People of Color (BIPOC) who are currently underrepresented in vulvar HP literature.6 Patient consent was obtained for publication and dissemination of these findings and all associated images. As per the second edition of the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS 2), case reports are exempt from research ethics board review. As the primary author, AS wrote the manuscript. SL performed the histopathologic assessment, provided the histopathological images, and provided manuscript editing and feedback. KL obtained patient consent and provided feedback, editing, and final approval on the manuscript. AS and KL were directly involved in the clinical care of this patient. The authors have nothing to report. None. The authors have no conflicts of interest. Data sharing is not applicable to this article as no new data were created or analyzed in this study.

During the course of the coronavirus disease 2019 (COVID-19) pandemic, reports of a new multisystem inflammatory syndrome in children (MIS-C) have been increasing in Europe and the United States (1-3). Clinical features in children have varied but predominantly include shock, cardiac dysfunction, abdominal pain, and elevated inflammatory markers, including C-reactive protein (CRP), ferritin, D-dimer, and interleukin-6 (1). Since June 2020, several case reports have described a similar syndrome in adults; this review describes in detail nine patients reported to CDC, seven from published case reports, and summarizes the findings in 11 patients described in three case series in peer-reviewed journals (4-6). These 27 patients had cardiovascular, gastrointestinal, dermatologic, and neurologic symptoms without severe respiratory illness and concurrently received positive test results for SARS-CoV-2, the virus that causes COVID-19, by polymerase chain reaction (PCR) or antibody assays indicating recent infection. Reports of these patients highlight the recognition of an illness referred to here as multisystem inflammatory syndrome in adults (MIS-A), the heterogeneity of clinical signs and symptoms, and the role for antibody testing in identifying similar cases among adults. Clinicians and health departments should consider MIS-A in adults with compatible signs and symptoms. These patients might not have positive SARS-CoV-2 PCR or antigen test results, and antibody testing might be needed to confirm previous SARS-CoV-2 infection. Because of the temporal association between MIS-A and SARS-CoV-2 infections, interventions that prevent COVID-19 might prevent MIS-A. Further research is needed to understand the pathogenesis and long-term effects of this newly described condition.

Teledermatology has become a widely accepted communication method in daily clinical practice, enabling remote care while showing strong agreement with in-person visits. Poor image quality remains an unsolved problem in teledermatology and is a major concern to practitioners, as bad-quality images reduce the usefulness of the remote consultation process. However, research on Image Quality Assessment (IQA) in dermatology is sparse, and does not leverage the latest advances in non-dermatology IQA, such as using larger image databases with ratings from large groups of human observers. In this work, we propose cross-domain training of IQA models, combining dermatology and non-dermatology IQA datasets. For this purpose, we created a novel dermatology IQA database, Legit.Health-DIQA-Artificial, using dermatology images from several sources and having them annotated by a group of human observers. We demonstrate that cross-domain training yields optimal performance across domains and overcomes one of the biggest limitations in dermatology IQA, which is the small scale of data, and leads to models trained on a larger pool of image distortions, resulting in a better management of image qualit

In 2004, Dai, Lathrop, Lutz, and Mayordomo defined and investigated the finite-state dimension (a finite-state version of algorithmic dimension) of a sequence $S \in Σ^\infty$ and, in 2018, Case and Lutz defined and investigated the mutual (algorithmic) dimension between two sequences $S \in Σ^\infty$ and $T \in Σ^\infty$. In this paper, we propose a definition for the lower and upper finite-state mutual dimensions $mdim_{FS}(S:T)$ and $Mdim_{FS}(S:T)$ between two sequences $S \in Σ^\infty$ and $T \in Σ^\infty$ over an alphabet $Σ$. Intuitively, the finite-state dimension of a sequence $S \in Σ^\infty$ represents the density of finite-state information contained within $S$, while the finite-state mutual dimension between two sequences $S \in Σ^\infty$ and $T \in Σ^\infty$ represents the density of finite-state information shared by $S$ and $T$. Thus ``finite-state mutual dimension'' can be viewed as a ``finite-state'' version of mutual dimension and as a ``mutual'' version of finite-state dimension. The main results of this investigation are as follows. First, we show that finite-state mutual dimension, defined using information-lossless finite-state compressors, has all of the pro

Resistance to cephalosporins and/or fluoroquinolones by Staphylococcus intermedius has remained low in Europe, with effective drugs generally available for systemic therapy in pets. However, multiresistant, mecA-positive S. intermedius isolated from dogs and cats is now emerging in Europe. Twelve S. intermedius isolates, highly resistant to at least five antimicrobial classes, were isolated from skin and ear infections in 11 dogs and a cat. The 12 isolates represented 23% of all S. intermedius submissions from one veterinary dermatology referral clinic in northern Germany to veterinary diagnostic laboratories during an 18-month period and resistance included cefalexin, methicillin and enrofloxacin. The animals had been referred to the clinic with recurrent superficial pyoderma, deep pyoderma, pododermatitis or chronic otitis, all unresponsive to systemic beta-lactam-antibiotics or fluoroquinolones. Infection resolved in 10 dogs and the cat on a combination of antimicrobial treatment and correction of underlying causes. Four dogs and a cat required systemic and topical therapy; in six dogs topical antimicrobial therapy alone was successful. Phenotypic and genotypic characteristics of the S. intermedius isolates were determined; species identification was confirmed by polymerase chain detection of thermonuclease genes (nuc) and the presence and expression of the gene conferring resistance to all beta-lactam antibiotics (mecA) were demonstrated in all; based on pulsed-field gel electrophoresis, six were indistinguishable, the others closely or possibly related. The emergence of multiresistant, mecA-positive S. intermedius in Europe is alarming. Zoonotic implications, awareness among veterinary laboratories and strategies for the use of antimicrobials in small animal practice need to be considered.

Racial bias in medicine, such as in dermatology, presents significant ethical and clinical challenges. This is likely to happen because there is a significant underrepresentation of darker skin tones in training datasets for machine learning models. While efforts to address bias in dermatology have focused on improving dataset diversity and mitigating disparities in discriminative models, the impact of racial bias on generative models remains underexplored. Generative models, such as Variational Autoencoders (VAEs), are increasingly used in healthcare applications, yet their fairness across diverse skin tones is currently not well understood. In this study, we evaluate the fairness of generative models in clinical dermatology with respect to racial bias. For this purpose, we first train a VAE with a perceptual loss to generate and reconstruct high-quality skin images across different skin tones. We utilize the Fitzpatrick17k dataset to examine how racial bias influences the representation and performance of these models. Our findings indicate that VAE performance is, as expected, influenced by representation, i.e. increased skin tone representation comes with increased performance

Medical vision-language models (VLMs) have shown promise as clinical assistants across various medical fields. However, specialized dermatology VLM capable of delivering professional and detailed diagnostic analysis remains underdeveloped, primarily due to less specialized text descriptions in current dermatology multimodal datasets. To address this issue, we propose MM-Skin, the first large-scale multimodal dermatology dataset that encompasses 3 imaging modalities, including clinical, dermoscopic, and pathological and nearly 10k high-quality image-text pairs collected from professional textbooks. In addition, we generate over 27k diverse, instruction-following vision question answering (VQA) samples (9 times the size of current largest dermatology VQA dataset). Leveraging public datasets and MM-Skin, we developed SkinVL, a dermatology-specific VLM designed for precise and nuanced skin disease interpretation. Comprehensive benchmark evaluations of SkinVL on VQA, supervised fine-tuning (SFT) and zero-shot classification tasks across 8 datasets, reveal its exceptional performance for skin diseases in comparison to both general and medical VLM models. The introduction of MM-Skin and S

Vision-language models (VLMs) are increasingly important in medical applications; however, their evaluation in dermatology remains limited by datasets that focus primarily on image-level classification tasks such as lesion recognition. While valuable for recognition, such datasets cannot assess the full visual understanding, language grounding, and clinical reasoning capabilities of multimodal models. Visual question answering (VQA) benchmarks are required to evaluate how models interpret dermatological images, reason over fine-grained morphology, and generate clinically meaningful descriptions. We introduce DermaBench, a clinician-annotated dermatology VQA benchmark built on the Diverse Dermatology Images (DDI) dataset. DermaBench comprises 656 clinical images from 570 unique patients spanning Fitzpatrick skin types I-VI. Using a hierarchical annotation schema with 22 main questions (single-choice, multi-choice, and open-ended), expert dermatologists annotated each image for diagnosis, anatomic site, lesion morphology, distribution, surface features, color, and image quality, together with open-ended narrative descriptions and summaries, yielding approximately 14.474 VQA-style ann

We report results of the CASE 2022 Shared Task 1 on Multilingual Protest Event Detection. This task is a continuation of CASE 2021 that consists of four subtasks that are i) document classification, ii) sentence classification, iii) event sentence coreference identification, and iv) event extraction. The CASE 2022 extension consists of expanding the test data with more data in previously available languages, namely, English, Hindi, Portuguese, and Spanish, and adding new test data in Mandarin, Turkish, and Urdu for Sub-task 1, document classification. The training data from CASE 2021 in English, Portuguese and Spanish were utilized. Therefore, predicting document labels in Hindi, Mandarin, Turkish, and Urdu occurs in a zero-shot setting. The CASE 2022 workshop accepts reports on systems developed for predicting test data of CASE 2021 as well. We observe that the best systems submitted by CASE 2022 participants achieve between 79.71 and 84.06 F1-macro for new languages in a zero-shot setting. The winning approaches are mainly ensembling models and merging data in multiple languages. The best two submissions on CASE 2021 data outperform submissions from last year for Subtask 1 and Su

BACKGROUND: Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical presentation, and outcomes of infection are poorly defined. METHODS: We formed an international collaborative group of clinicians who contributed to an international case series to describe the presentation, clinical course, and outcomes of polymerase-chain-reaction-confirmed monkeypox virus infections. RESULTS: We report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having ≤10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported. CONCLUSIONS: In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.

Dapsone (4,4'-diaminodiphenylsulfone) is an aniline derivative belonging to the group of synthetic sulfones. In 1937 against the background of sulfonamide era the microbial activity of dapsone has been discovered. Shortly thereafter, the use of dapsone to treat non-pathogen-caused diseases revealed alternate antiinflammatory mechanisms that initially were elucidated by inflammatory animal models. Thus, dapsone clearly has dual functions of both: antimicrobial/antiprotozoal effects and anti-inflammatory features similarly to non-steroidal anti-inflammatory drugs. The latter capabilities primarily were used in treating chronic inflammatory disorders. Dapsone has been investigated predominantly by in vitro methods aiming to get more insights into the effect of dapsone to inflammatory effector cells, cytokines, and/or mediators, such as cellular toxic oxygen metabolism, myoloperoxidase-/halogenid system, adhesion molecules, chemotaxis, membrane-associated phospholipids, prostaglandins, leukotrienes, interleukin-8, tumor necrosis factor α, lymphocyte functions, and tumor growth. Moreover, attention has been paid to mechanisms by which dapsone mediates effects in more complex settings like impact of lifespan, stroke, glioblastoma, or as anticonvulsive agent. Additionally, there are some dermatological investigations in human being using dapsone and its metabolites (e.g., leukotriene B4-induced chemotaxis, ultraviolet-induced erythema). It could be established that dapsone metabolites by their own have anti-inflammatory properties. Pharmacology and mechanisms of action are determining factors for clinical use of dapsone chiefly in neutrophilic and/or eosinophilic dermatoses and in chronic disorders outside the field of dermatology. The steroid-sparing effect of dapsone is useful for numerous clinical entities. Future avenues of investigations will provide more information on this fascinating and essential agent.

A major barrier to developing vision large language models (LLMs) in dermatology is the lack of large image--text pairs dataset. We introduce DermaSynth, a dataset comprising of 92,020 synthetic image--text pairs curated from 45,205 images (13,568 clinical and 35,561 dermatoscopic) for dermatology-related clinical tasks. Leveraging state-of-the-art LLMs, using Gemini 2.0, we used clinically related prompts and self-instruct method to generate diverse and rich synthetic texts. Metadata of the datasets were incorporated into the input prompts by targeting to reduce potential hallucinations. The resulting dataset builds upon open access dermatological image repositories (DERM12345, BCN20000, PAD-UFES-20, SCIN, and HIBA) that have permissive CC-BY-4.0 licenses. We also fine-tuned a preliminary Llama-3.2-11B-Vision-Instruct model, DermatoLlama 1.0, on 5,000 samples. We anticipate this dataset to support and accelerate AI research in dermatology. Data and code underlying this work are accessible at https://github.com/abdurrahimyilmaz/DermaSynth.

Deep Learning approaches in dermatological image classification have shown promising results, yet the field faces significant methodological challenges that impede proper evaluation. This paper presents a dual contribution: first, a systematic analysis of current methodological practices in skin disease classification research, revealing substantial inconsistencies in data preparation, augmentation strategies, and performance reporting; second, a comprehensive training and evaluation framework demonstrated through experiments with the DINOv2-Large vision transformer across three benchmark datasets (HAM10000, DermNet, ISIC Atlas). The analysis identifies concerning patterns, including pre-split data augmentation and validation-based reporting, potentially leading to overestimated metrics, while highlighting the lack of unified methodology standards. The experimental results demonstrate DINOv2's performance in skin disease classification, achieving macro-averaged F1-scores of 0.85 (HAM10000), 0.71 (DermNet), and 0.84 (ISIC Atlas). Attention map analysis reveals critical patterns in the model's decision-making, showing sophisticated feature recognition in typical presentations but sig

A set $S\subseteq V$ is a dominating set of $G$ if every vertex in $V - S$ is adjacent to at least one vertex in $S$. The domination number $γ(G)$ of $G$ equals the minimum cardinality of a dominating set $S$ in $G$; we say that such a set $S$ is a $γ$-set. A generalization of this is partial domination which was introduced in 2017 by Case, Hedetniemi, Laskar, and Lipman [3,2] . In partial domination a set $S$ is a $p$-dominating set if it dominates a proportion $p$ of the vertices in $V$. The p-domination number $γ_{p}(G)$ is the minimum cardinality of a $p$-dominating set in $G$. In this paper, we investigate further properties of partial dominating sets, particularly ones related to graph products and locating partial dominating sets. We also introduce the concept of a $p$-influencing set as the union of all $p$-dominating sets for a fixed $p$ and investigate some of its properties.

Class-Incremental Learning (CIL) aims to learn new classes over time without forgetting previously acquired knowledge. The emergence of foundation models (FM) pretrained on large datasets presents new opportunities for CIL by offering rich, transferable representations. However, their potential for enabling incremental learning in dermatology remains largely unexplored. In this paper, we systematically evaluate frozen FMs pretrained on large-scale skin lesion datasets for CIL in dermatological disease classification. We propose a simple yet effective approach where the backbone remains frozen, and a lightweight MLP is trained incrementally for each task. This setup achieves state-of-the-art performance without forgetting, outperforming regularization, replay, and architecture based methods. To further explore the capabilities of frozen FMs, we examine zero training scenarios using nearest mean classifiers with prototypes derived from their embeddings. Through extensive ablation studies, we demonstrate that this prototype based variant can also achieve competitive results. Our findings highlight the strength of frozen FMs for continual learning in dermatology and support their broad