Necrotic Keratinocytes Research Articles

Vulvar Lichenoid Dermatoses With Emphasis on the Distinction Between Lichen Sclerosus and Lichen Planus: A 10-Year Study.

Lichen planus (LP) and lichen sclerosus (LS) are the most common vulvar lichenoid dermatoses. The diagnostic challenges are due to site-specific variation in microscopic appearance and small-sized biopsies. Authentication of diagnostic criteria to distinguish LS and LP to uncover any resemblance or divergence in presentation of these conditions is attempted. Cases of vulvar LP and LS diagnosed between January 2012 to December 2022 were included. The clinical details included age, presenting symptoms, examination findings, and other organ involvement. Histopathological analysis of epidermal, dermal, and adnexal findings was done. There were 28 cases of vulvar LP and 72 cases of LS, with a median age of 51 and 60 years, respectively. Depigmentation and atrophy were the major clinical features in LS, whereas ulcers/erosions and erythema were more prevalent in LP with a significantly higher incidence of oral involvement. The most diagnostic feature in LS was diffuse dermal sclerosis (76.8%) and interstitial pattern of inflammation (81.4%), whereas the characteristic features in LP cases was a lichenoid pattern of inflammation (85.7%), necrotic keratinocytes, and lymphocytic exocytosis. In 44.4% of LS, unconventional features like compact orthokeratosis, parakeratosis, thickened/wedge-shaped hypergranulosis, and sawtooth rete pegs were noted. Lichen sclerosus with lichenoid inflammation (21.4%) mimicked LP, from which it was distinguished by presence of thickened or diminished granular layer with basal melanin absence (60%) and dermal homogenization (80%). Although the classical, well-established variant of LS poses no diagnostic difficulty, the unconventional variant may mimic LP. Identification of the subtle histological clues demonstrated in this study can help to arrive at the correct diagnosis.

Pembrolizumab-Induced Lichen Planus in a Patient with Metastatic Pulmonary Giant Cell Carcinoma: A Case Report and Literature Review

Ιmmune checkpoint inhibitors (ICIs) have revolutionized the management of advanced cancers. Nevertheless, the oncologic response is often achieved at the cost of immune-related adverse events (irAEs). We present a case of an immune-mediated lichen planus (LP) and a literature review of similar cases. A 60-year-old man, who is being treated with pembrolizumab for a pulmonary giant cell carcinoma since April 2022, presented in November 2022 with a pruritic eruption that appeared two weeks ago. Examination showed bright purple confluent scaly papules on wrists, proximity of limbs, back and buttocks and palmar keratoderma made of violaceus papules covered with reticular white striae. Histological examination revealed an epidermal hyperplasia, vacuolization of the basal layer, necrotic keratinocytes and a band-like subepidermal lymphocytic infiltrate with many eosinophils. The diagnosis of an immune-related LP was retained. Pembrolizumab was withheld because of the severity and the extension of the lesions. Superpotent topical steroids were prescribed with a significant improvement of the rash within 3 weeks. Immune-mediated lichenoid euptions represent one of the most frequent dermatologic irAEs. In our patient, the onset seven months after the initiation of ICIs, the infiltrate rich in eosinophils, and the rapidly diffused character are indications of an immuno-mediated LP.

Psoriazis hastalarında klasik/klasik olmayan histopatolojik bulguların psoriasis alt tiplerine, hastalık süresine ve şiddetine, anatomik bölgeye ve klinik görünüme göre değişimi

Objective: Although histopathological examination is considered the gold standard in the diagnosis of psoriasis, it has limited usefulness in patients with non-classical histopathological and/or clinical presentations. The aim of this study was to examine the distribution of classical and non-classical histopathological findings according to psoriasis subtype, disease duration, disease severity, biopsy site, and classical/non-classical presentation.
 Methods: We retrospectively reviewed the records of 160 patients with histopathologically confirmed psoriasis. Classical and non-classical histopathological features were determined according to dermatopathology textbooks and literature. Patients were categorized according to disease duration (≤12 and >12 months) and disease severity (Psoriasis Area Severity Index [PASI] ≤10 and >10) at presentation, and classical/non-classical presentation (based on morphology, distribution, nail pitting, and family history).
 Results: The most common classical histopathological findings were regular acanthosis (99.4%), confluent parakeratosis (96.3%), blood vessels, dilated (93.1%), hyperkeratosis (89.4%), and suprapapapillary plate thinning (89.4%). The most common non-classical histopathological findings were superficial perivascular dermal infiltration (81.3%) and spongiosis (53.8%). Hyperkeratosis (p=0.044) and intraepidermal lymphocyte accumulation (p=0.042) were more frequent in patients with a disease duration >12 months. The presence of Munro microabscess (p=0.010) and stratum basale necrotic keratinocytes (p=0.031) were observed more frequently in patients with PASI >10. Significant hyperkeratosis (p=0.024) and suprapapillary plate thinning (p=0.027) were more common in trunk biopsies compared to other locations. Spongiosis (p=0.005) and intraepidermal lymphocytes (p=0.008) were more common in patients with non-classical clinical presentation.
 Conclusion: Non-classical histopathological findings can be observed in patients with psoriasis. Clinical features should be considered when evaluating classical/non-classical histopathological findings during diagnosis.

A Case of Proliferative and Necrotizing Otitis Externa in a Scottish Fold Shorthair Cat

In this case report, the aim was to contribute to understanding PNOE's clinical presentation, histopathological features, and successful treatment approaches, emphasizing the significance of accurate diagnosis and appropriate management in affected felines. Proliferative necrotic otitis externa (PNOE) is a very rare skin disease of unknown etiology affecting the vertical ear canal and the concave surface of the auricle, which may be accompanied by secondary yeast or bacterial infections. In this case 8-month-old Scottish fold shorthair cat has fragile, papillomatous growths and caseous purulent exudate in the ear canal was presented. The differential diagnosis of this condition includes otoacariasis, plasma cell pododermatitis, papillomavirus and chronic bacterial or yeast otitis externa. Despite antimicrobial and antiparasitic based previous treatments, the lesions persisted. Histopathological examination revealed acanthotic epidermis, necrotic keratinocytes, and inflammatory cell infiltrates. Treatment involved methylprednisolone injection, topical pomades, and systemic antibiotics. The cat showed improvement after initial treatment week, with regression of lesions and cessation of ear discharge. Follow-up visits demonstrated continued improvement, and after two months, minimal sequelae remained. In conclusion, despite the unknown etiology of PNOE, the disease is quite responsive to immunosuppressive therapy, which is beneficial for both diagnosis and treatment.

Anti-PL-7, anti-Ro/SSA, anti-Mi-2, and anti-TIF1-γ correlate with specific patterns of histopathologic features in dermatomyositis: An analysis of 39 skin biopsy specimens from 25 patients.

In dermatomyositis (DM), myositis-specific and myositis-associated antibodies have been correlated with clinical features. It is unknown if histopathologic findings in lesional skin biopsies correlate with serologic subtypes of DM. A retrospective chart review of patients with DM was performed. Patients with myositis antibodies and DM lesional skin biopsies were included in the study. Skin biopsies were reviewed by blinded dermatopathologists for 20 histopathologic features. There was a statistically significant (p < 0.05) association between anti-PL-7 serology and decreased degree of vacuolar degeneration, necrotic keratinocytes, and thickening of the epidermal basement membrane. Anti-aminoacyl tRNA synthetase (anti-ARS) antibodies had the same significant negative association with degree of vacuolar degeneration, necrotic keratinocytes, and thickening of the epidermal basement membrane. A similar pattern was seen with an anti-cytoplasmic serology; where there was a significant association with an increased degree of vacuolar degeneration and necrotic keratinocytes, and a nonsignificant trend of minimally thickened epidermal basement membrane. There was a statistically significant association between anti-Ro/SSA serology and increased degree of vacuolar degeneration. Anti-TIF1-γ serology was significantly associated with the increased presence of necrotic keratinocytes and pigment incontinence, and displayed a pattern of increased neutrophils. There was a significant association between anti-Mi-2 antibodies and pigment incontinence, as well as between myositis-specific antibodies and pigment incontinence. A statistically significant positive association was found between nuclear antibodies and degree of vacuolar degeneration, thickened epidermal basement membrane, pigment incontinence, and epidermal atrophy. In patients with DM, some specific serotypes, including anti-PL-7, anti-Ro/SSA, anti-Mi-2, and anti-TIF1-γ, may have characteristic histopathologic features.

Exantema en enfermedad por virus de inmunodeficiencia humana, ¿manifestación de infección o reacción alérgica?

A male patient presented with a maculopapular, non-pruritic rash, without palmoplantar involvement, after receiving treatment with trimethoprim/sulfamethoxazole for seven days due to gastrointestinal symptoms. After taking a complete medical history and using fourth-generation tests confirmed HIV infection. On the fifth day of antiretroviral treatment, he presented new erythematous lesions with thick, pruritic scaling, facial edema and eosinophilia. A skin biopsy reported lichenoid dermatitis, with spongiosis, vacuolar degeneration of the basal layer, necrotic keratinocytes and eosinophil infiltrate, characteristics that favor drug reaction. The treatment consisted of interrupting the combined therapy, using systemic corticosteroids, antihistamines and since it was not a severe condition, antiretroviral treatment restarted without complications.

Individual Keratinocyte Necroses in the Epidermis Are Apoptotic Keratinocytes in the Skin.

The patient was a 44-year-old woman with Stevens-Johnson syndrome due to receiving Baktar® (sulfamethoxazole trimethoprim) medication at our outpatient dermatology clinic. The epidermis, dermis, and subcutaneous adipose tissue samples showed numerous necrotic keratinocytes in the epidermis. Apoptotic nuclei were visualized as diaminobenzidine brown deposits with immunoperoxidase staining for cleaved caspase-3. The cleaved caspase-3-positive findings were consistent with eosinophilic material that appeared to be necrotic cells within the epidermis. Therefore, these eosinophilic materials may be apoptotic bodies. Generally speaking, eosinophilic cells are considered necrotic keratinocytes, especially in Japan. To the best of our knowledge, no studies have used apoptotic immunohistochemical markers to examine whether these structures are apoptotic in a human specimen.

Preventive effects of inotodiol on polyinosinic–polycytidylic acid-induced inflammation in human dermal fibroblasts

Double-strand RNA(dsRNA), which can induce inflammation, can be generated by necrotic keratinocytes in the skin environment. As an analog of dsRNA, polyinosinic–polycytidylic acid (poly(I:C)) is used to induce inflammation via the Toll-like Receptor 3 (TLR3) signaling pathway. Inotodiol, isolated from Inonotus obliquus, known as Chaga mushroom, is a natural lanostane-type triterpenoid with significant pharmacological activity and notable anti-inflammatory effects. However, the functions of inotodiol on dsRNA-induced inflammation in human dermal fibroblast (HDFs) remains unclear. In this study, we evaluated the anti-inflammatory effects of inotodiol inflammation induced on by poly(I:C) in HDFs. After pre-treatment with inotodiol, poly (I:C) was used to induce inflammation. Subsequently, mRNA expression and protein secretion of inflammatory cytokines, as well as TLR3 signaling protein levels were assessed. Inflammatory cytokines IL-1β, IL-6, and TNF-α′s increased mRNA expression by poly(I:C) in HDFs was significantly suppressed in the inotodiol pre-treatment group in a dose-dependent manner. A similar pattern was evaluated in the protein levels of these three cytokines. The inflammatory signals of TLR3 via p-IKK, p-p38, and NF-κB was reduced by inotodiol pre-treatment. Taken together, inotodiol possesses strong anti-inflammatory activity against poly(I:C)-induced inflammation in HDFs. Therefore, our findings support potential application of inotodiol as an effective anti-inflammatory agent in cosmetics.

DP12 Painful oral keratosis and skin lesions: a paraneoplastic diagnostic conundrum

Abstract A 70-year-old man was referred to oral medicine with extensive, painful oral hyperkeratosis affecting the tongue, buccal mucosa and palate. Medical history included a previous diagnosis of prostate cancer. Histology from multiple oral biopsy specimens showed only hyperparakeratosis and acanthosis, with no fungi or dysplasia. Owing to the absence of oral inflammation, the pain was treated as neuropathic. The patient then developed skin lesions and dermatology review was requested. Skin examination revealed marked hyperkeratotic, verrucous plaques affecting the extensor surfaces of the limbs and dorsal hands, as well as the plantar feet bilaterally. The nails were unaffected. There was violaceous discolouration of the pinnae. Given the history of prostate cancer, a paraneoplastic process was suspected. Two incisional biopsies were taken, which showed epidermal acanthosis with necrotic and dyskeratotic keratinocytes throughout the epidermis. There was a dense eosinophilic inflammatory infiltrate. Direct and indirect immunofluorescence was negative. The appearances were suggestive of a paraneoplastic phenomenon, including acrokeratosis paraneoplastica. Haematological investigations identified an IgG monoclonal paraproteinaemia with raised kappa:lambda ratio. Following further investigation, including bone marrow biopsy and positron emission tomography computed tomography, a diagnosis of monoclonal gammopathy of undetermined significance was made by haematology. A repeat bone marrow biopsy 7 months later confirmed evolution to myeloma. As CRAB criteria (hypercalcaemia, renal insufficiency, anaemia and bone lesions) were absent, a period of observation followed. A trial of oral steroids improved the cutaneous eruption, but he developed significant side-effects. Oral mycophenolate, methotrexate and acitretin were used as steroid-sparing agents, with a poor clinical response. The skin lesions progressed to a widespread psoriasiform eruption on the trunk and lower limbs with the formation of bullae. Further biopsies showed an eosinophil-rich infiltrate with negative immunofluorescence, raising the possibility of an eosinophilic dermatosis of haematological malignancy. After 2 years, given the worsening skin symptoms, it was decided to commence bortezomib, cyclophosphamide and dexamethasone (VCD) chemotherapy. Despite four cycles of VCD treatment, the skin lesions worsened and as the paraprotein levels did not reduce, treatment was stopped. Subsequently, further elevations in serum free light chains prompted treatment with lenalidomide. This resulted in a marked improvement in the skin and reduced pain from the oral lesions, as well as a reduction in serum free light chains. Acrokeratosis paraneoplastica (Bazex syndrome) is characterized by digital hyperkeratosis and paronychia, which may progress to involve the limbs and trunk. Eosinophilic dermatosis of haematological malignancy is characterized by a pruritic, papular skin eruption with a vesiculobullous component. This case presents a diagnostic conundrum, with evolving features of two different paraneoplastic conditions.

CPC09 New-onset agminated Spitz naevi following hypopigmented pityriasis lichenoides chronica

Abstract A 9-year-old girl presented to dermatology with erythematous scaly patches affecting her legs and arms, and hypo­pigmented patches affecting the trunk. She was otherwise fit and well, with no preceding illness or new medications. Treatment with mometasone 0.1% and an emollient was unsuccessful. Two years later, she had continued to develop new hypopigmented patches, as well as dark clustered naevi on the trunk. An incisional biopsy was taken from a hypopigmented patch of the right abdomen and one of the new naevi from the right hip. Incisional biopsy of the hypo­pigmented patch showed scattered necrotic keratinocytes in the epidermis with mild hydropic degeneration of basal cells and a mild superficial and perivascular lymphohistiocytic infiltrate in the dermis, consistent with pityriasis lichenoides chronica (PLC). Incisional biopsy of an eruptive naevus showed a junctional proliferation of melanocytes with overlying epidermal hyperplasia and hyperkeratosis and transepidermal elimination of melanin. Nests of epithelioid melanocytes were present at the rete tips, with no pagetoid spread and no atypia, consistent with an eruptive Spitz naevus. PLC is a benign lymphoproliferative disorder, typically presenting with erythematous scaly papules that relapse and remit. However, cases of PLC presenting with hypopigmentation alone have also been reported, as in this case, which can be part of a postinflammatory dyspigmentation or active disease (Elbendary A, Abdel-Halim MR, Youssef R et al. Hypopigmented lesions in pityriasis lichenoides chronica patients: are they only post-inflammatory hypopigmentation? Aust J Dermatol 2021; 63:68–73). The clustered pattern of Spitz naevi in this patient is termed agminated Spitz naevus. Eruptive disseminated and agminated Spitz naevi are much rarer than the solitary presentation. Triggers of eruptive Spitz naevi include pregnancy, blistering disorders and topical tacrolimus, and in one case following pityriasis lichenoides et varioliformis acuta (Mazzurco J, Menssen K, Schapiro B et al. Eruptive disseminated Spitz nevi in a 26-year-old African-American woman. Int J Dermatol 2012; 51:1270–1), while agminated Spitz naevi are reported to occur after radiotherapy and sunburn, and to arise in naevus spilus or congenitally hypo- or hyperpigmented patches. No cases of malignancy in agminated or eruptive disseminated Spitz naevi have been reported. In this case, the new onset of agminated Spitz naevi may have been triggered by the inflammatory process of PLC. As far as we can ascertain, there have not been previous cases of this published in the literature. Our patient’s hypopigmented areas have now started to self-resolve and we have planned for ongoing monitoring of the agminated Spitz naevi.

Acute onset dermatomyositis with NXP‐2 antibodies after Sars‐CoV‐2 vaccination in a 20‐year‐old female

AbstractDermatomyositis is an autoimmune connective tissue disease with variable cutaneous and systemic manifestations. While multiple cutaneous reactions to SARS‐CoV‐2 vaccination have been described, vaccine‐associated emergence of dermatomyositis has rarely been reported. Cases of deterioration in pre‐existing connective tissue diseases have been described following both vaccination and COVID‐19 infection. A potential mechanism of immune system activation and dysregulation has been suggested. This case describes acute onset of dermatomyositis in a young female, presenting with classic cutaneous features including Gottron papules, Holster sign and proximal nail fold erythema, accompanied with myalgia and fatigue. Laboratory findings of elevated creatine kinase and myositis‐specific autoantibodies confirmed the diagnosis, with supportive histological findings of necrotic keratinocytes at the dermoepidermal junction. In keeping with the typical progression of dermatomyositis with NXP‐2 autoantibodies, cutaneous findings resolved rapidly, while systemic manifestations slowly improved with treatment. Thorough investigations for underlying malignancy were completed. This case adds to the limited medical literature surrounding these cases and further highlights the importance of consideration of SARS‐CoV‐2 vaccination in the immunologic pathophysiology of autoimmune connective tissue diseases.

Genetic Phylocomparative Analysis of B2L, F1L Genes in Orf Virus Isolated from Felid Infected Sheep

Contagious ecthyma virus Large, oval, double-stranded DNA viruses from the family Poxviridae they are distinct from other poxviruses due to their unusual spiral coat. Orf virus encoded highly conserved F1L gene, B2L gene, which codes for highly immunogenic envelope protein. Orf lesions were observed on the upper and lower lips, upper and/or lower eyelids, and around the mouth and nose of sheep. This study evaluated the histology and genetics of Orf virus in AL-Qadisyah sheep infected with infectious ecthyma. Positive histology is defined by the presence of subcorneal pustules, hydropic degeneration of necrotic keratinocytes, and epidermal hyperplasia with pronounced rete ridges. Samples were fixed in paraffin and sectioned into 5m slices. PCR on DNA-extracted samples was positive for both the B2L and F1L genes. Four positive samples were sequenced and recorded in GeneBank, and phylogenetic analysis was performed. Histopathology and clinical symptoms can aid in the diagnosis of infectious ecthyma rapidly and affordably, whereas PCR distinguishes between identical diseases in endemic regions. Analyzing the divergence between the inferred amino acid sequences of the incomplete B2L gene in different strains from Iraq OK336711.1, OK336710.1, and other Indians, we found that two locations contain different amino acid changes, resulting in a nucleotide and amino acid identity of 97.8% and 97.6%, respectively. The F1L envelope protein of the Iraqi strain OK330734.1 was comparable to those of China and India, while the envelope protein of the Italian strain OK330733.1 was identical to that of Italy.

Clinical Manifestations and Management of Terbinafine‐Induced Acute Generalized Exanthematous Pustulosis

Background. Acute generalized exanthematous pustulosis (AGEP) is a rare and serious adverse reaction of terbinafine. Understanding AGEP and terbinafine is primarily based on case reports. The purpose is to explore the clinical characteristics of terbinafine‐induced AGEP, and to provide reference for clinical diagnosis and treatment. Methods. Case reports and original studies of terbinafine‐induced AGEP were retrieved by searching Chinese and English databases from January, 1991, to May 31, 2022. Results. The median age of the 32 patients (17 males and 15 females) was 55 years (range: 6–84). The median time to onset of AGEP is 8 days (range: 1–77) and is usually accompanied by fever (&gt;38°C) and elevated neutrophil levels (&gt;8000/mm3). Four patients (12.5%) had oral mucosal involvement, and 10 patients (31.3%) developed postpustular desquamation. The lesions were mainly distributed in the trunk (43.8%), the whole body (34.4%), and the extremities (53.1%). Skin biopsy revealed subcorneal pustules (65.6%), intraepidermal cavernous pustules (43.8%), necrotic keratinocytes (15.6%), spongy hyperplasia (25.0%), neutrophil exocytosis (34.4%), and papillary dermal edema (40.6%). AGEP resolved completely in all patients at a median time of 12 days (range: 2–90) after discontinuation of terbinafine and symptomatic therapy. Conclusion. Clinicians should be aware that terbinafine‐induced AGEP is a rare cutaneous adverse reaction. AGEP usually occurs within 2 weeks after administration and has a good prognosis after discontinuation.

Dermoscopic Findings of Clonal Seborrheic Keratosis and Pigmented Basal Cell Carcinoma in the Skin of Color Patients - A Comparison.

Dermoscopic Findings of Clonal Seborrheic Keratosis and Pigmented Basal Cell Carcinoma in the Skin of Color Patients - A Comparison.

Dermoscopy and reflection confocal microscope features of pigmented prurigo.

Pigmented prurigo (PP) is a chronic and recurrent inflammatory skin disease. PP is not common clinically, but it is easily misdiagnosed because of its diversified clinical manifestations in different stages. We retrospectively analyzed the clinical, histopathological, dermoscopy, and reflectance confocal microscopy (RCM) features of 20 patients diagnosed as PP. The female predominance ratio was revealed with male to female of 1:4. Seven female patients were on a diet (without staple food) and one patient had a history of diabetes. Eight cases were suffered in spring, six cases in winter, three cases in summer, and three cases in autumn. Multiple sites were involved in 13 cases. Four patients had urticarial papules and plaques. Nineteen patients had erythematous papules with reticular distribution, of which 14 cases accompanied reticulate hyperpigmentation, four cases with papulovesicle, and two cases accompanied with pustules. One patient only showed reticulate hyperpigmentation. In the early lesions, dermatoscopy showed pink oval lesions, punctate or linear vessels, and pale yellow rings around the skin lesions. RCM is characterized by spongiosis, spongy vesicle, neutrophils scattered in the epidermis, which was consistent with epidermis spongiosis, neutrophils infiltrating into the upper epidermis and necrotic keratinocytes in histopathology. In the fully developed lesions, dermatoscopy showed pink lesions with brown pigment granules in the center and linear vessels in the edge. RCM showed that demarcation of epidermis and dermis is not clear, and inflammatory cells can be seen in the upper dermis and histopathologically lesions assumed a patchy lichenoid pattern, and the inflammatory cells infiltrating the dermis were dominated by lymphocytes. In the late lesions, dermatoscopy showed grainy grayish-brown or yellowish-brown pigmentation surrounding the hair follicle merging with each other. RCM showed that pigment granules were increased on the ring of basal cells, inflammatory cells were sparsely infiltrated in the dermal papilla and superficial layer, and epidermis slightly hyperplastic, with melanophages and a few lymphocytes infiltrating the superficial dermis in histopathology. PP is easily misdiagnosed and not always occurs in those on a restrictive diet. A combination of dermatoscopy and RCM is helpful for its diagnosis of PP.

353 Immunomodulatory role of NF-kB signalling pathway in skin inflammation

IKK/NF-kB signalling controls inflammation and cell death and is important to maintain tissue homeostasis. Keratinocyte-specific deletion of IKK2 (IKK2E-KO) leads to TNFR1-dependent skin inflammation in mice. IKK2E-KO mice showed increased numbers of apoptotic and necrotic keratinocytes, and upregulation of inflammatory cytokines mediators in the epidermis. We proposed that keratinocyte death could trigger inflammation. Receptor Interacting Protein Kinase (RIPK1) induces cell death via kinase activity-dependent functions.

S2422 A Lichen for the Esophagus: A Rare Case of Esophageal Lichen Planus

Introduction: Lichen planus is an inflammatory condition of the skin and mucosal membranes. Sites of disease are variable and esophageal involvement is uncommon. We highlight a case of esophageal lichen planus masquerading as eosinophilic esophagitis. Case Description/Methods: A 59-year-old female with a past medical history of hypothyroidism status post thyroidectomy presents with progressive dysphagia and odynophagia to solids for 3 years. Symptoms initially began after thyroidectomy. Evaluation by ENT was notable for inflammatory changes of the oropharynx for which PPI trial was given for clinical features of silent reflux. Despite a 2-month course of therapy, symptoms persisted. Videofluoroscopic swallow study was unremarkable without evidence of aspiration or penetration. Subsequent EGD was notable for exudates, linear furrowing, and rings to suggest the diagnosis of eosinophilic esophagitis. Esophageal biopsy pathology features, however, showed band-like lymphocytic infiltration of the lamina propria and civatte bodies within the squamous epithelium consistent with esophageal lichen planus. Unfortunately, the patient was lost to follow up and subsequent treatment was unable to be initiated. Discussion: Esophageal lichen planus is an exceedingly rare entity with less than 100 documented case reports. It is likely underdiagnosed given that it can mimic other esophageal entities, such as eosinophilic esophagitis as seen in our patient. As such, histologic examination is necessary to identify key features of esophageal lichen planus which include lymphocytic infiltrates of the lamina propria as well as civatte bodies, which represent necrotic keratinocytes. Esophageal lichen planus has a tendency to be chronic and require topical or systemic therapy with steroids. Stricture development will typically require dilatation. Clinicians should consider esophageal lichen planus as part of their differential for dysphagia especially given the potential for malignant transformation to squamous cell carcinoma, which has been reported in 1-2% of cases.

Human monkeypox virus infection in an immunocompromised man: trial with tecovirimat

Human monkeypox virus infection in an immunocompromised man: trial with tecovirimat

Adult-onset Still's disease: A disease at the crossroad of innate immunity and autoimmunity.

Adult-onset Still’s disease (AOSD) is a rare disease affecting multiple systems and organs with unknown etiology, and the clinical symptoms are usually described as spiking fever, arthritis, evanescent salmon-pink eruptions, lymphadenopathy, splenomegaly, and other manifestations. The laboratory indicators are not specific, often presenting as increased leukocyte counts and neutrophil percentage, elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), hyperferritinemia, and increased inflammatory factors. ANA, ENA, and RF are negative. According to those unspecific clinical presentations and laboratory findings, infection, tumor, connective tissue disease, and other diseases must be ruled out before diagnosis. The diagnosis of AOSD is a great challenge for clinicians. The mechanism of AOSD pathogenesis is complicated and still being studied. There is a new opinion that atypical persistent skin eruptions (APSEs) with specific histological manifestations are unique for AOSD, and APSEs might be on a spectrum with classical evanescent eruptions. Studies on APSEs showed that IL-1β and IFN-γ are strongly correlated with the pathogenesis of necrosis keratinocytes in APSEs. IL-1β is strongly involved in inflammatory disease when it is abnormal, and plays an important role in the pathogenesis of neutrophil dermatosis. In the early stage of AOSD, skin lesions appear to be evanescent urticaria-like eruptions accompanied by fever, and only neutrophils infiltrate around the blood vessels in the dermis pathologically. As the course of the disease progresses, IL-1β is gradually released. Through the stimulation of other inflammatory factors and the influence of unknown factors, IL-1β gradually infiltrates into the stratum corneum and finally accumulates around the necrotic keratinocytes of the stratum corneum. However, the detailed mechanism is still unknown. IFN-γ could play a pro-inflammatory or regulatory role in some disorders. IL-1β can enhance the expression of IFN-γ, and IFN-γ can cause keratinocyte apoptosis by activating the autocrine of caspase. Also, several pieces of evidence indicate that adaptive immunity is also involved in the pathogenesis of AOSD. Increased α-soluble receptors of IL-2 may suggest T-cell activation and proliferation in AOSD patients. Increased IL-4- and IFN-γ-producing T cells were found in active AOSD and related to disease severity. Frequencies of Treg cells in AOSD were significantly lower and were inversely correlated with disease severity. According to these, more and more researchers have reached a consensus that AOSD is a disease at the crossroads of innate immunity and autoimmunity. In this review, we will provide a comprehensive insight into AOSD, describing research progress and the immunological mechanism contribution to the disease. In the meantime, different treatment options and the efficacy and safety of various biologic agents are also discussed. A further understanding of AOSD requires closer cooperation among doctors from different departments, and this review will provide a new idea for diagnosis and therapeutic options.

Drug-Induced vs. Viral Maculopapular Exanthem-Resolving the Dilemma.

Maculopapular exanthem is a commonly encountered presentation in routine clinical practice, and differentiation between its two most common etiologies, i.e., viral- and drug-induced, often poses a diagnostic dilemma. Clinical, hematological and biochemical investigations are seldom reliable in distinguishing between a drug reaction and a viral exanthem. Certain key histopathological features such as the presence of a moderate degree of spongiosis, extensive basal cell damage with multiple necrotic keratinocytes and dermal infiltrate rich in eosinophils or lymphocytes and histiocytes may favor a drug exanthem, while distinctive epidermal cytopathic changes and lymphocytic vasculitis point towards a viral etiology. Similarly, notable immunohistochemical markers such as IL-5, eotaxin and FAS ligand may support a diagnosis of a drug-induced maculopapular eruption. Histopathological and immunohistochemical evaluations may help in distinguishing between the two etiologies when faced with a clinical overlap, especially in patients on multiple essential drugs when drug withdrawal and rechallenge is not feasible.