Perivascular Inflammatory Infiltrates Research Articles

Immunohistochemical Analyses of Monkeypox Skin Lesions with MPXV A29 and A35 Antibodies: A Novel Insight for Clinical-Histopathological Forms.

The aim of this study was to describe the clinical, histopathological, and immunohistochemical characteristics of MPX and offer meaningful insights into the clinicopathology of MPX. We recruited eight men who had sex with men diagnosed with MPX based on positive results from MPX Virus (MPXV)-specific polymerase chain reaction. Skin biopsies were obtained from four selected lesions, including typical and atypical lesions. Histopathological examinations of atypical solitary ulceration revealed infiltrating inflammatory cells predominantly composed of plasma cells and lymphocytes, forming a "sleeve" around the superficial vessels of the dermis. These features might be misinterpreted as indicative of cutaneous syphilis infection. Meanwhile, typical pustular lesions displayed central necrotic epidermis accompanied by perivascular inflammatory infiltrate dominated by neutrophils, as well as ballooning and reticular degeneration of keratinocytes. Additionally, multinucleated keratinocytes and eosinophilic cytoplasmic inclusions known as Guarnieri's bodies were also observed. Importantly, this study represented the pioneering report on immunohistochemical detection of MPXV A29 and A35 proteins in skin lesions, distinguishing it from previous studies that focused on detecting vaccinia virus protein. The anti-MPXV A29 antibody exhibited robust cytoplasmic staining specifically within affected keratinocytes in both adjacent epidermis and hair follicles, thereby it could contribute to the diagnosis of MPX, especially for cases with atypical skin lesions.

An Unusual Skin Finding in a Rare Case of Goltz Syndrome

Abstract Introduction/Objective Goltz Syndrome (Focal Dermal Hypoplasia) is a rare X linked dominant genetic disorder with various dermatologic, musculoskeletal and neurologic manifestations, secondary to a mutation in the PORCN gene. Skin findings include telangiectasias, raspberry-like papillomas (angiofibroma like lesions), nodular fat herniation, xerosis and photosensitivity. Lesions are bilateral, and asymmetrically distribututed along the lines of Blasco. The adipocytic lesions can be diagnosed via a skin biopsy showing adipose tissue in the superficial epidermis and dermis or via molecular techniques showing a mutation in the PORCN gene. Here we report a case of Goltz Syndrome with unique dermal findings. Methods/Case Report A male infant presented at birth with mild diffuse xerosis, large hypopigmented and depigmented atrophic patches and plaques and multiple pink yellow red exophyitic soft papules distributed asymetrically across the body along the lines of Blascho. Additionally the patient had clinodactly, widely spaced nipples, extra pads of fat in the toes and philtrum and fingernails with longitudal ridges and lateral nail plate deviation. A diagnosis of Goltz syndrome was made via molecular analysis that showed mosiacism at C.502G>A (p.Gly168Arg) in the PORCN gene. The patient had a very superficial 2-3 mm erosion at the intersection between the scrotum and perineum. At 18 months, this had grown to finger like projections and eventually grew into multiple tan red exophytic warty papillomatous telangactatic like lesions measuring 3.0 x 0.8 cm that were painful and bled easily. A biopsy of this lesion showed focal mild epidermal hyperplasia and elongation of the rete ridges with wide spread diffuse vascular proliferation with multiple ectactic vessels along with mild dermal and perivascular inflammatory infiltrates. Also noted was infiltration of mature adipose tissue in the superficial epidermis and dermis. We preformed elastin and trichrome stains to identify if this lesion was reactive in nature or de novo. Our results showed retained elastin staining with a negative trichrome eluding to a denovo process. Additionally GLUT1 was negative, ruling out an infantile hemangioma. The above findings in this lesion do not represent any previously described dermatologic entity. Results (if a Case Study enter NA) NA Conclusion This is a rare and unique dermatologic finding of a case of Goltz sydrome, which itself is a rare disorder. In our literature review, this is the only case of Goltz Syndrome thusfar to have presented with this unique skin lesion.

Pulmonary Hyalinizing Granuloma: Case Report and Discussion of Diagnostic Challenges and Terminology.

Pulmonary hyalinizing granuloma (PHG) is a rare, benign condition characterized by slow-growing pulmonary nodules, often mimicking malignant lesions radiologically. Its pathogenesis is unclear but is thought to result from an exaggerated immune response to persistent antigenic stimuli. This report presents a case of a 71-year-old male with PHG, incidentally detected during imaging for acute appendicitis. Diagnostic challenges arose due to the radiological resemblance to metastatic disease, and inadequate biopsy samples. Surgical resection revealed fibrocollagenous nodules with perivascular inflammatory infiltrates. Immunohistochemistry and special stains excluded malignancy and infection. The clinical course of PHG is typically benign, with surgery being the treatment of choice for solitary lesions. However, the current terminology may be misleading, as the lesions are not true granulomas but rather fibrosing lesions. Further research is needed to clarify the underlying pathophysiology and improve diagnostic accuracy.

Purified L-glutaminase effects against multidrug-resistant Pseudomonas aeruginosa in experimental vaginosis model: An immunological and histopathological observation

The antimicrobial activity of crude and purified L-glutaminase (EC 3.5.1.2), obtained from Lactobacillus gasseri, was evaluated against multidrug-resistant Pseudomonas aeruginosa in the in vivo vaginosis condition. The L-glutaminase possessed significant antimicrobial and anti-biofilm formation activity against multi-drug resistance P. aeruginosa, which were confirmed in the BALBc rat vaginosis model, together with its effects on the immunological and histopathological aspects. The untreated animals showed heavy vaginitis, characterized by sub-epithelial edema and infiltration of mononuclear leukocytes, perivascular heavy inflammatory cells infiltration in the vaginal tissue, and moderate stromal edema. However, the L-glutaminase treatment exhibited no changes in vaginal tissue structure with normal appearance of the epithelium and lamina propria with marked repair of the vaginal section when compared with normal, uninfected, control group A. The immunomodulatory actions of the L-glutaminase were confirmed by observance of higher concentrations of tumor necrosis factor-γ (TNF-γ), and interleukin −12 (IL-12) in treated animals, while the interleukin-10 (IL-10) was higher in the infected, untreated animals' sera samples. Therefore, the L-glutaminase showed corrective and healing actions, which were observed through histopathological observations of the vaginal tissue. The investigations led to imply that L-glutaminase may have the potential to be an effective antimicrobial agent for preventing and inhibiting bacterial growth, as well as inhibiting the biofilm formation in the P. aeruginosa-originated vaginosis. The observations may be of promising value for future clinical use.

Clinical and Genetic Heterogeneity of Nuclear Envelopathy Related Muscular Dystrophies in an Indian Cohort.

Nuclear envelopathies occur due to structural and/or functional defects in various nuclear envelope proteins such as lamin A/C and lamin related proteins. This study is the first report on the phenotype-genotype patterns of nuclear envelopathy-related muscular dystrophies from India. In this retrospective study, we have described patients with genetically confirmed muscular dystrophy associated with nuclear envelopathy. Data on clinical, laboratory findings and muscle MRI were collected. Sixteen patients were included with median age at onset of 3 years (range: 1 month - 17 years). Three genes were involved: LMNA (11, 68.75%), EMD (4, 25%) and SYNE1 (1, 6.25%). The 11 patients with LMNA variants were Congenital muscular dystrophy (MDCL)=4, Limb Girdle Muscular Dystrophy (LGMD1B)=4 and Emery-Dreifuss Muscular Dystrophy (EDMD2)=3. On muscle biopsy, one patient from each laminopathy phenotype (n = 3) revealed focal perivascular inflammatory infiltrate. Other notable features were ophthalmoparesis in one and facial weakness in one. None had cardiac involvement. Patients with EDMD1 had both upper (UL) and lower limb (LL) proximo-distal weakness. Cardiac rhythm disturbances such as sick sinus syndrome and atrial arrhythmias were noted in two patients with EDMD1. Only one patient with variant c.654_658dup (EMD) lost ambulation in the 3rd decade, 18 years after disease onset. Two had finger contractures with EMD and SYNE1 variants respectively. All patients with LMNA and SYNE1 variants were ambulant at the time of evaluation. Mean duration of illness (years) was 11.6±13 (MDCL), 3.2±1.0 (EDMD2), 10.4±12.8 (LGMD1B), 11.8±8.4 (EDMD1) and 3 (EDMD4). One patient had a novel SYNE1 mutation (c.22472dupA, exon 123) and presented with UL phenotype and prominent finger and wrist contractures. The salient features included ophthalmoparesis and facial weakness in LMNA, prominent finger contractures in EMD and SYNE1 and upper limb phenotype with the novel pathogenic variant in SYNE1.

Exploratory phase I study of HF1K16 for the treatment of patients with refractory/recurrent advanced glioma: Preliminary efficacy and mechanism as a monotherapy.

e14030 Background: The absence of I.O success in advanced glioma treatment suggests that a deeper understanding of the brain tumor and the immune microenvironment is critical. It is well-documented that refractory/recurrent glioma has an immunosuppressive nature. One frequent observation is the high level of circulating myeloid-derived suppressor cells (MDSCs). We conducted a exploratory study to assess an immunomodulatory approach for relieving immune suppression employing HF1K16, a liposome all-trans retinoic acid (ATRA) suspension. Methods: This Phase I study (NCT05388487) comprise a conventional 3+3 dose escalation plus an advanced glioma-specific expansion arm. Eligible patients had prior confirmed advanced solid tumor and failed standard treatment. HF1K16 infusions were administered in 21-day cycles (q.o.d days 1-14). Prior to and during treatment, peripheral blood mononuclear cells were collected and analyzed with flow cytometry to monitor the changes in myeloid cell phenotype and T cell composition. Survival data were calculated as it is difficult to determine the timing of progression for immunotherapies owing to pseudoprogression. Results: As of Feb 2th, 2024, 14 recurrent/refractory glioma patients including 6 males and 8 females had been enrolled in this study. 2 of them withdrew before finished 1st cycle. 7 had received treatment for at least 3 cycles and 1 had achieved CR after 15 cycles. For the 8 primary diagnosed grade IV glioma patients, the mOS is 7.8m, and 6 (75%) are alive. The mOS for the primary dignosed grade II/III is 13.7m and 100% patients are alive (n=4). There is 1 recurrent GBM patent who had received 5 cycles of treatment. MRI showed an enlargement of tumor lesion while KPS score remained >90. A surgical resection was performed and we subsequently studied the posttreatment tumor specimens (window of opportunity). IHC and flow cytometry analysis revealed prominent perivascular and intratumoral inflammatory infiltrate, containing CD8+CTL cells and HLA-DR expressing cells. Conclusions: While the interpretation of our data is limited by the small sample size, the results provide an encouraging signal and warrants further assessment. Patient recruitment continues with anticipated completion in 2024. Clinical trial information: NCT05388487 . [Table: see text]

DRESS as a rare differential diagnosis in eosinophilia, skin rash and acute hepatitis

A 21-year-old female patient presented with fever, pharyngitis, lymphadenopathy and generalized exanthema that had started 2 weeks prior. Allergies were not known, the family and travel history were negative. Due to depression, Duloxetine had been taken for 1.5 years, and due to bipolar disorder, a treatment with Lamotrigine was started four weeks prior but was stopped because of increased transaminase levels. Laboratory findings on admission showed eosinophilia (1.327 /nl), lymphocytosis and acute hepatitis (GOT 428 U/l, GPT 438 U/l) with deranged coagulation. Inflammatory parameters were increased. Ultrasound revealed hepatosplenomegaly with ascites. Acute viral or parasitic infection was excluded serologically. A skin biopsy showed a perivascular inflammatory infiltrate, compatible with a drug reaction. An inflammatory infiltrate was found in the liver biopsy, consistent with drug-induced hepatitis. Cough, dyspnea and pleural effusion occurred. In summary of the findings and with the help of the RegiSCAR-Score, the diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) could be made. Under high-dose prednisolone therapy, a gradual decrease of transaminases and reconstitution of liver synthesis could be observed.In patients with eosinophilia, lymphadenopathy, acute hepatitis and generalized exanthema, DRESS is a rare but-due to its potentially life-threatening consequences-important differential diagnosis. The most important measure is to stop the suspected inducing medication immediately. Severe cases should be treated with high-dose systemic corticosteroids.

Diagnosing the Dermatologic Blues: Systematic Review of the Rare Conundrum, Psychogenic Purpura.

Psychogenic purpura is an idiopathic psychodermatologic condition of recurrent, painful purpura precipitated by psychological stress, predominantly affecting young females. Little consensus exists on the diagnostic guidelines for this rare condition, often resulting in costly, unnecessary, and stressful investigations as well as prolonged hospital admissions. With this first up-to-date systematic review of 134 cases of psychogenic purpura in over a decade, we aim to thoroughly investigate the diagnostic strategy and treatment regimens used in the last decade. With a sooner diagnosis, patient stress and nosocomial ecchymoses can be minimized, and treatment can be expedited. We conducted a literature review of 4 databases (PubMed, Ovid Embase, Ovid MEDLINE, and Web of Science) on October 5, 2022 that yielded 46 full-text articles, which were reviewed and extracted by 2 independent reviewers. We analyzed a total of 134 cases, consisting largely of females (125/134, 93.3%) with purpura on the upper (103/134, 76.9%) or lower limbs (112/134, 83.6%). Apart from a paresthesia prodrome, patients commonly experienced headaches, malaise, and arthralgia or myalgia. Approximately 70% (95/134) of patients reported a physiological or psychological stressor or psychiatric diagnosis before the development of the purpura. Laboratory testing almost always revealed unremarkable results. The intradermal washed autoerythrocyte sensitization test was positive in 98% (42/43) of cases. Histopathology biopsy findings commonly revealed dermal erythrodiapedesis or hemorrhage (n=34) and perivascular inflammatory infiltrates (n=17). Approximately 42% (56/134) of patients received a novel psychiatric diagnosis, with depression being the most common (40/72, 56%). In both patients with and those without a novel psychiatric diagnosis, observation, counseling, treatment with antidepressants (ie, selective serotonin reuptake inhibitors), and psychotherapy (ie, cognitive behavioral therapy) prevailed in the resolution of the purpura. Due to the unclear etiology and infrequent presentation of this condition, it remains a diagnosis of exclusion based on clinical suspicion evaluating the presence of stressors or psychiatric comorbidities and exclusion of systemic conditions. Clinical confirmation can be sought through a positive autoerythrocyte sedimentation test, characteristic histopathology findings, and remission of purpura after psychiatric treatment.

Collagen-Filler Injection Associated Dermopathy and COVID-19

COVID-19 and cosmetic skin-fillers are two prevalent topics of today’s medicine, yet their interaction is not sufficiently studied. This article is based on a clinico-morphological case where the patient, a 37-year-old female, visited the clinic with complaints of painless palpable subcutaneous pathologic nodular lesions at the site of collagen cosmetic filler injection after severe acute respiratory syndrome coronavirus 2 infection. In order to verify the pathological processes of the lesions, punch biopsy of the affected skin was taken, and histological, histochemical, and immunohistochemical studies were conducted. Atrophy, acanthosis, parakeratosis with vacuolisation of nuclei of the epidermis; sclerosis and abnormal deposition of collagen fibres in the subepithelial layer of dermis; and vasculitis with endothelial hypertrophy and lymphoid perivascular infiltration (CD3 lymphocytes and CD68 macrophages) were found. Spike and nuclear capsid proteins of severe acute respiratory syndrome coronavirus 2 were localised in cells of perivascular inflammatory infiltrates, endothelial cells, and epithelium of glands and epidermis of the skin. The association between the dermatopathy in COVID-19 virus infection and cosmetic fillers were established. The authors discuss and hypothesise possible autoimmune processes that lead to autoimmune vasculitis.

Surgical treatment of tracheal stenosis during Covid-19 era: a single-center experience and lessons learnt on the field

SARS-CoV2 outbreak led to several healthcare system challenges, especially concerning respiratory support to Covid-19 patients. In the first 2 years of pandemic (2020–2021), we assisted to a marked increase of post-invasive mechanical ventilation (IMV) tracheal stenosis incidence, many of them requiring surgical treatment, namely resection and primary end-to-end anastomosis. Our aim is to describe our experience during the abovementioned biennium, focusing on postoperative outcomes of patients who have had Covid-19 (“post-Covid”). We retrospectively collected pre-, intra- and postoperative data on all patients who underwent tracheal surgery for benign stenosis in our Unit from May 2020 to October 2021, including previous Covid-19. Comparison between “post-Covid-19” and “non-Covid-19” groups’ outcomes was then performed. Patients were 9 males and 6 females, and mean age was 57.4 ± 13.21 years. Nine patients had previous Covid-19 (60%). All patients underwent multidisciplinary preoperative evaluation. Almost every operation was conducted by cervicotomy, and the mean length of the resected specimen was 23.9 ± 6.5 mm. Postoperative complications were: dysphonia (3 cases), wound infection (1), bleeding (1), ab-ingestis pneumonia (1), anastomosis dehiscence (2), and stenosis recurrence (1). Thirty-day mortality rate was 6.7% (1 patient). No significant differences between “post-Covid-19” and “non-Covid-19” groups were identified. Pathology revealed, in 5 “post-Covid-19” patients, signs of vasculitis or perivascular inflammatory infiltrate. Tracheal stenosis’ surgical treatment has always been known as a challenging procedure because of high perioperative morbidity and mortality rates. Our experience shows that previous Covid-19 and ongoing pandemic did not significantly affect perioperative outcomes of patients who underwent tracheal resection and primary end-to-end anastomosis in a high-volume Center and after multidisciplinary workup.Graphical abstract

Clinical, Neurophysiologic, and Pathologic Features in Patients With Early-Onset Postradiation Neuropathy.

The objective of this study was to study early-onset radiation-induced neuropathy reviewing neurologic course, steroid response, and available nerve biopsies. Patients coded with radiation-induced neuropathy within 6 months of radiation were reviewed from January 1,1999, to August 31, 2022. Patients had to have electrodiagnostically confirmed neuropathy localized within or distal to radiation fields. Neurologic course and nerve biopsies were reviewed. Twenty-eight patients (16 male and 12 female patients, mean age 63.8 years) were identified. The average radiation dose was 4,659 cGy (range 1,000-7,208). Tumor infiltration was not observed on MRI and PET. Postradiation onsets averaged 2 months (range 0-5). Localizations included brachial (n = 4) plexopathies, lumbosacral (n = 12) plexopathies, radiculopathies (n = 10), and mononeuropathies (n = 2). Neuropathic pain (n = 25) and weakness (n = 25) were typical. The clinical courses were subacute monophasic (n = 14), chronic progressive (n = 8), or static (n = 1), and 5 were without follow-up. Nerve biopsies (n = 8) showed an inflammatory ischemic process with perivascular inflammatory infiltrates (n = 7) or microvasculitis (n = 2). Nine patients, 7 with monophasic courses, received steroid burst therapy with symptom improvement in 8. No patients recovered entirely back to baseline. In contrast to chronic radiation-induced neuropathy, early-onset patients most commonly have painful monophasic courses with residual deficits, possibly steroid responsive. An ischemic inflammatory pathogenesis is suggested.

A fatal case of fulminant group: a streptococcal infection in a neonate

BackgroundFulminant hemolytic streptococcal infection is a condition of sudden onset and rapidly progressing septic shock caused by Streptococcus pyogenes. It causes beta (complete) hemolysis. Although type A Streptococcus occurs more frequently, all streptococci that cause beta-hemolysis are eligible as causes. This report describes a rare autopsy case of fulminant group A streptococcal infection in a neonate.Case presentationA 16-day-old girl, 3300 g, born by spontaneous delivery at 41 weeks 1 day, experienced a 1-day history of low-grade fever, malaise, and a few hours of cyanosis and anuria, prompting her parents to bring her to the hospital. Her eldest brother, who lived with her, had been infected with Streptococcus approximately one month earlier, and had been treated with ten days of antibiotics. The infant died three hours after presentation. Autopsy findings indicated her to be 52 cm in length, weighing 3585 g, with medium build and normal nutrition. Her lungs were slightly oligemic with decreased volumes. The liver and kidneys were mildly enlarged. The spleen was markedly enlarged. The adrenal glands showed diffuse cortical hemorrhage (Fig. 1). There was some thymic atrophy (thymus weight 7.4 g, < 1 SD below the mean). Histopathological findings included chronic and neutrophilic infiltration of the tonsils and multiple septic emboli containing cocci in the lungs. Perivascular inflammatory cell infiltrates were observed in the lungs, myocardium, kidneys, adrenal glands, brain, meninges, and liver, with micro-necrotic changes in the kidneys and liver. Fibrin thrombi were observed in multiple renal glomeruli. Hemophagocytosis by macrophages was observed in the spleen, liver, lymph nodes, bone marrow, and adrenal glands. Immunostaining showed positive results for group A Streptococcus antibody in the tonsils, with bacterial masses. Blood cultures were positive for group A Streptococcus pyogenes.ConclusionsBecause of the lower respiratory tract infection and suspected sibling transmission, in addition to the adrenal hemorrhages, a diagnosis of fulminant sepsis with group A Streptococcus pyogenes with associated Waterhouse–Friderichsen syndrome was made.

DP14 Going against the grain: eosinophilic dermatosis presenting as erythema gyratum repens

Abstract Erythema gyratum repens (EGR) is a rare, paraneoplastic rash with a characteristic woodgrain appearance. It is heavily associated with malignancies, including lung, oesophageal and breast cancers. However, other conditions can mimic EGR, including leucocytoclastic vasculitis, immunobullous and papulosquamous conditions. We report an unusual presentation of eosinophilic dermatosis with an EGR-like pattern, not associated with malignancy. A 67-year-old woman presented with a 2-week history of a pruritic eruption on her legs. It initially started with three small circular erythematous macules on the right leg and one on the left leg. Over the course of a few days, the three macules evolved into large concentric annular patches simulating woodgrain, which raised the clinical suspicion of EGR. After a week, the patches began to blister with accentuation of some of the blisters on the edge of the annular patches. She denied any previous history of skin problems or changes in medication and was otherwise well with no systemic symptoms, including fever. In view of the almost 70% chance of an underlying malignancy, she was thoroughly investigated. Her full blood count, eosinophil count, liver function test, renal profile and serum C3 and C4 were normal. Skin basement membrane/desmosome antibodies and Borrelia burgdorferi IgG and IgM antibodies were also negative. Histology revealed prominent epidermal spongiosis with some corneal and intraepidermal vesicles that were cell-poor and contained only red blood cells. The underlying dermis showed prominent papillary dermal oedema with a brisk interstitial and superficial/deep perivascular mixed inflammatory infiltrate containing numerous eosinophils but no obvious flame figures. There was also eosinophil infiltration into the underlying subcutaneous fat. Direct immunofluorescence was negative. The histological pattern was that of an eosinophil-rich dermatitis with vesiculation; the history and morphology of the eruption were not compatible with bullous insect bites. An eosinophilic dermatosis such as eosinophilic cellulitis presenting with an EGR-like pattern was considered to be the most likely possibility for her presentation. Computed tomography of the neck, thorax, abdomen and pelvis, bidirectional endoscopy and mammography revealed no malignancies. She was treated with prednisolone 30 mg daily for 10 days with Elocon® ointment, and the eruption improved remarkably leaving postinflammatory colour changes that subsequently resolved. We would like to raise the awareness that an EGR-like pattern can be found in several other dermatoses, including eosinophilic dermatosis, and woodgrain pattern is not always equivalent to EGR or a high risk of associated malignancies (Table 1).Table 1Erythema gyratum repens-like dermatosesLeucocytoclastic vasculitisImmunobullousPapulosquamousBullous pemphigoidPsoriasisEpidermolysis bullosa acquisitaPityriasis rubra pilarisLinear IgA dermatoses

Leucoderma in Buffaloes (Bubalus bubalis) in the Amazon Biome.

Leucoderma is a condition that affects the skin and hair of animals, causing depigmentation and acromotrichia. In buffaloes, this condition results in significant economic losses for the production chain due to its impact on the leather trade. This study aimed to investigate the epidemiological and clinicopathological aspects of leucoderma in buffaloes in the Amazon biome and describe the prophylactic treatment to control the disease. The study included 40 buffaloes, 16 males and 24 females, aged between 1 and 10 years, and were of the Murrah, Jafarabadi, Mediterranean, and Murrah × Mediterranean crossbreed breeds. The animals were raised without mineral supplementation. The clinical signs observed in the animals included acromotrichia and depigmentation, with varying degrees and distribution of skin lesions. Histological examination of the epidermis showed interrupted melanin production, mild dermal fibrosis, mild perivascular mononuclear inflammatory infiltrate, and pigmentary incontinence. None of the animals had the genotype for albinism. After 120 days of mineral supplementation based on the use of copper sulfate, the clinical signs of leucoderma regressed. There was no predisposition by breed, sex, or age for the occurrence of the disease. The regression of skin lesions after proper mineral supplementation suggests that copper deficiency may be considered an important factor for the occurrence of leucoderma in buffaloes in the Amazon biome.

Porcine circovirus type 3: immunohistochemical detection in lesions of naturally affected piglets.

This study aimed to evaluate the relationship between porcine circovirus type 3 (PCV3) viral load and histopathological findings in perinatal piglet tissues and to develop an immunohistochemical method for detecting the virus in lesions. The quantitative polymerase chain reaction (qPCR) cycle threshold (Ct) when amplifying PCV3 DNA and the area of perivascular inflammatory infiltrates in different organs [central nervous system (CNS), lung, heart, liver, spleen, and lymph nodes] were compared. To develop an immunohistochemistry technique, rabbit sera were produced against PCV3-capsid protein peptides selected using bioinformatic analyses. The assay was initially implemented using a tissue sample previously tested using qPCR and in situ hybridization to optimize the procedure and reagent dilutions. To evaluate immunohistochemistry performance, tissue samples from another 17 cases were analyzed using standardized parameters. The most common microscopic lesion was multisystemic periarteritis, with associated vasculitis, as the mesenteric vascular plexus is one of the most affected organs. Other tissues, such as the heart, lung, CNS, and skeletal muscle, were also affected. Comparison of the Ct values for different tissues showed no significant difference, except in lymphoid organs (spleen and lymph nodes), which had significantly higher viral loads than the CNS tissues. There was no correlation between Ct values and perivascular inflammatory infiltrates. PCV3 immunohistochemistry revealed granular immunolabeling, mainly in the cytoplasm of cells in the vascular mesenteric plexus, heart, lung, kidney, and spleen.

Dermal Hypersensitivity Reaction to Semaglutide: Two Case Reports.

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of antidiabetic agents that work by inducing insulin secretion and inhibiting release of glucagon in a glucose-dependent manner. They are especially promising given their long duration of action, decreased risk of hypoglycemia, and added benefit of weight loss. Semaglutide is a GLP-1 receptor agonist that has been approved for type II diabetes and chronic weight management in obese adults. Cases of hypersensitivity reactions have been previously reported in patients taking GLP-1 receptor agonists dulaglutide and liraglutide. However, to our knowledge, there have been no reports of hypersensitivity reactions to semaglutide. Here, we present two cases of dermal hypersensitivity reactions in patients taking semaglutide for type II diabetes. In the first case, a 75-year-old woman who had been taking semaglutide for 10 months presented with an eruption on her legs, back, and chest for 3 months duration. Histology showed a subepidermal blister with eosinophils, suggestive of a drug hypersensitivity reaction. In the second case, a 74-year-old white man who had been taking semaglutide for 1 month presented with an eruption on the bilateral flanks and lower abdomen for 3 weeks duration. Histology revealed perivascular inflammatory cell infiltrate with eosinophils, also suggestive of a drug hypersensitivity reaction. Both patients began experiencing resolution of their symptoms within 1 month of discontinuing semaglutide. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.6550 Citation: Ouellette S, Frias G, Shah R, et al. Dermal hypersensitivity reaction to semaglutide: Two case reports. J Drugs Dermatol. 2023;22(4):413-415. doi:10.36849/JDD.6550.

Neuropathology of yellow fever autopsy cases

BackgroundYellow fever is a viral hemorrhagic fever caused by yellow fever virus, a mosquito-borne flavivirus. Despite an effective vaccine, major outbreaks continue to occur around the world. Even though it is not a proven neurotropic virus, neurological symptoms in more severe clinical forms are frequent. The understanding of this apparent paradox is still rarely addressed in literature.MethodsThe brains of thirty-eight patients with yellow fever confirmed by RT-PCR, who underwent autopsy, were analyzed morphologically to identify and characterize neuropathological changes. The data were compared with brains collected from individuals without the disease, as a control group. Both cases and controls were subdivided according to the presence or absence of co-concurrent septic shock, to exclude changes of the sepsis associated encephalopathy. To verify possible morphological differences between the yellow fever cases groups, between the control groups, and between the cases and the controls, we applied the statistical tests Fisher's exact test and chi-square, with p values < 0.05 considered statistically significant.ResultsAll cases and controls presented, at least focally, neuropathological changes, which included edema, meningeal and parenchymal inflammatory infiltrate and hemorrhages, and perivascular inflammatory infiltrate. We did not find an unequivocal aspect of encephalitis. The only parameter that, after statistical analysis, can be attributed to yellow fever was the perivascular inflammatory infiltrate.ConclusionsThe neuropathological findings are sufficient to justify the multiple clinical neurologic disturbances detected in the YF cases. Since most of the parameters evaluated did not show statistically significant difference between cases and controls, an explanation for most of the neuropathological findings may be the vascular changes, consequent to shock induced endotheliopathy, associated with stimulation of the immune system inherent to systemic infectious processes. The statistical difference obtained in yellow fever cases regarding perivascular infiltrate can be can be explained by the immune activation inherent to the condition.

Cutaneous Sporotrichosis of Face with Verrucous Lesions over Nose, Successfully Treated with a Combination of Itraconazole and Terbinafine: A Case Report.

Dear Editor, A 13-year-old boy presented with nasal erythematous, crusted, confluent papules, and nodules persisting for approximately 35 days [Figure 1]. The patient denied contact with sick cats but mentioned playing in the bushes. The clinical diagnosis was cutaneous sporotrichosis, and he started treatment with itraconazole 100 mg per day, which was administered orally for 10 days and then increased to 200 mg per day. The exudate from the skin lesions was directly examined by a potassium hydroxide test, which was negative for fungal presence. At 25°C, a mycosal media culture of the exudate revealed colonies resembling Sporothrix sp, which appeared membranous, beige, wrinkled, and with a blackened halo [Figure 2]. At 37°C, phenotypic reversal for creamy colonies with beige and colorless verse was observed, thus demonstrating dimorphism. The lactophenol cotton blue stain revealed hyaline septate hyphae [Figure 3]. On day 44 of itraconazole treatment alone, the lesions became severely crusted, demonstrating no improvements. Thus, 250 mg of oral terbinafine was added to the treatment regimen. On day 60 of itraconazole use, a skin biopsy was performed. Grocott silver stain revealed rare samples of fungal structures [Figure 4]. Histopathology showed acanthosis of the epidermis, areas with perivascular mononuclear inflammatory infiltrate and fibrosis [Figure 5]. On day 226 of itraconazole and day 182 of terbinafine use, clinical improvement was noted, indicating the end of oral antifungal drugs [Figure 6]. The patient underwent Laser Erbium YAG, an ablative laser, to achieve favorable aesthetic results for the scar and uniformization of the skin of the nasal region.Figure 1: Infiltrated erythematous nodules of sporotrichosis on the nose with verrucous appearanceFigure 2: Culture at 25°C, showing colonies of membranous, beige, wrinkled with a blackened halo, resembling Sporothrix speciesFigure 3: The hyaline septate hyphae of Sporothrix spp. with one pyriform microconidia in daisy arrangement (lactophenol cotton blue stain, ×40)Figure 4: Grocott silver stain presenting a fungal structures (40x)Figure 5: Acanthosis of the epidermis, areas with perivascular mononuclear inflammatory infiltrate, and intense remodeling of dermal collagen with fibrosis. (H and E, 10x)Figure 6: Clinical improvement after terbinafine and itraconazole use. Only residual erythema, papules and nodulesSporotrichosis is a subcutaneous mycosis caused by a thermodimorphic fungus, Sporothrix spp., most commonly S. brasiliensis, S. schenckii, and S. globosa.[1] The lesions manifest in different clinical forms: mainly lymphocutaneous, fixed, cutaneous, disseminated, and extracutaneous. Recently, the incidence of various diseases caused by Sporothrix has been increasing in Brazil, particularly a high disease rate in urban areas. Felines have been reported as a new source of infection that spreads diseases.[2] Itraconazole is a first-line treatment for Sporothrix, but some strains, mainly S. brasiliensis, are resistant.[3–5] Moreover, itraconazole content sometimes does not match the concentrations indicated by manufacturers.[3] Itraconazole has certain pharmacokinetic concerns because of several drug interactions. For example, a high gastric pH reduces its bioavailability. Terbinafine is an alternative drug that can effectively treat cutaneous sporotrichosis, and it is affordable and has fewer interactions with other drugs.[1,4,5] To improve therapeutic outcome, itraconazole has been combined with a second drug and demonstrated good results, for example, with supersaturated potassium iodide (SSKI) solution.[6] SSKI is an alternative for cutaneous forms, which is primarily used for infants. However, compared with terbinafine, SSKI has side effects and issues, such as a lack of standardized commercial formulation and unknown mechanisms of action.[1,4] Studies describing the use of itraconazole with terbinafine are limited. In vitro, terbinafine and itraconazole have synergistic effects because both disrupt ergosterol synthesis in the cell membrane of fungi at different stages. This mechanism is beneficial due to accelerated response against chromoblastomycosis, onychomycosis, and sporotrichosis, where facial lesions can cause aesthetic stigmas and affect the quality of life of patients. In conclusion, the combination of terbinafine and itraconazole can effectively inhibit disease progression faster and thus prevent excessive fibrosis and scars.[5,7–10] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

An Unusual Presentation of Lichen Striatus.

An Unusual Presentation of Lichen Striatus.

Immunohistochemical expression of connective tissue growth factor in skin tags

Background:Skin tags (STs), also known as acrochordons, are the most common fibro epithelial skin tumours. Connective tissue growth factor (CTGF) is a novel peptide that exhibits platelet-derived growth factor-like activities and is produced by skin fibroblasts after activation with transforming growth factor-beta (TGF-β).The aim of this research was to evaluate the immunohistochemical expression of connective tissue growth factor in skin tags to provide an insight about its role in the pathogenesis of the disease. Methods: This prospective case-control research was carried out on 20 skin tags’ cases clinically and histopathologically diagnosed, and 10 healthy individuals of matched age and sex, served as control group.All cases were subjected to dermatological examination, skin biopsy and immunohistochemical staining. Results: There was significant difference between the cases and controls regarding epidermal (Acanthosis, hyperkeratosis, papillomatosis) and dermal changes (perivascular inflammatory infiltrate, fibroblasts, collagen arrangement) (P value