Intralesional Certolizumab for Refractory Lupus Pernio.

This case report describes a patient with refractory lupus pernio that responded to treatment with a series of intralesional certolizumab injections.

Superficial solitary fibrous tumor masquerading as a dermoid cyst: a case report.

Background: Solitary fibrous tumors (SFTs) are relatively rare spindle cell neoplasms uncommonly seen in dermatology practice. Initially discovered as a pleural tumor, SFTs have also been found in extra-pleural sites including the skin and soft tissues. When arising within the dermis or subcutis they are termed superficial SFTs, where they often present as solitary, unilateral, slow growing superficial masses. Histologically, they are composed of spindle cells arranged in a "patternless" pattern with hemangiopericytoma-like vessels dispersed throughout. Historically, CD34, CD99 and Bcl-2 immunohistochemical (IHC) stains were used to differentiate SFTs from other spindle cell neoplasms, however these markers are not entirely specific. Recent discovery of a disease defining NGFI-A binding protein 2 (NAB2)-signal transducer and activator of transcription 6 (STAT6) fusion gene has led to the use of STAT6 IHC staining to help verify the diagnosis of SFTs, particularly in unexpected sites. Case Description: We report a case of a 23-year-old woman with a slowly growing lateral supra-orbital mass, clinically concerning for a dermoid cyst, which was subsequently discovered to be a SFT on pathologic examination, with the diagnosis being verified by STAT6 immunostaining. Conclusions: SFTs are rarely encountered in dermatologic practice, however, must be kept on the differential of subcutaneous nodules, including those occurring in young adults. Due to the rarity of these tumors in clinical practice, a proposed algorithm for the approach to management of SFTs is included, guided by a validated, histology-driven, metastatic risk assessment tool, to help guide other clinicians confronted by these tumors.

The eyes have it: when skin findings prompt referral to ophthalmology.

PURPOSE OF REVIEW: Co-presentation of ocular and cutaneous conditions is common and prompt recognition of known associations may be imperative to sight-saving intervention. There are currently limited reviews in the pediatric literature addressing comorbid ocular and dermatologic presentations. Recent diagnostic and therapeutic advances have drastically altered the prognostic landscape for several disease states when recognition and referral are timely. The aim of this report is to examine important oculocutaneous disease associations with emphasis on management of ocular complications and appropriate referral practices to ophthalmology specialists. RECENT FINDINGS: Oculocutaneous associations can be broadly classified into four etiologic categories: infectious, inflammatory, genetic, and medication/nutrition induced pathology. Several conditions in all four categories have had recent advances in their etiologic understanding, diagnostic evaluation, and therapeutic approach. Thematically, these advances highlight increasing disease prevalence of certain conditions, previously unrecognized pediatric relevance of others, updated diagnostic criteria, and newer categories of iatrogenic illness induced by advances in medical therapy. SUMMARY: This review is designed to provide the pediatric practitioner a vignette-based high-level overview of both common and sight threatening associations that should prompt consideration for ophthalmology consultation. Conditions were selected based on relevance, relative urgency, and recent advances in their etiologic/therapeutic understanding.

Oral Tranexamic Acid for the Treatment of Melasma: A Case Series and Novel Dosing Regimen.

Melasma is a common disorder affecting millions of people around the world.1 It is a condition that can disrupt one’s self-esteem and overall quality of life.2 Melasma is characterized by hyperpigmented macules and patches on the face.1 The pathophysiology of melasma is widely unknown, although multiple triggers have been identified.3 Among the triggers, sun exposure is considered to be the most important factor.3 A variety of topical treatments exist for melasma, however most of these options often lead to subpar results. Due to this, novel treatments such as oral tranexamic acid (TXA) have emerged.4,5 Our case series demonstrates the effectiveness and safety profile of utilizing oral TXA to treat recalcitrant melasma and highlights a possible dosing regimen that can be used for the novel therapy. J Drugs Dermatol. 2022;21(4):393-398. doi:10.36849/JDD.6663.

Erythrodermic Psoriasis Exacerbated by Bupropion.

Erythroderma is a rare, potentially life-threatening presentation of psoriasis that can be triggered by medication reactions. Bupropion is indicated for major depressive disorder (Wellbutrin®, GlaxoSmithKline, Research Triangle Park, NC), smoking cessation (Zyban®, GlaxoSmithKline, Research Triangle Park, NC), and weight loss (when in formulation with naltrexone ER; Contrave®, Orixegen Therapeutics, La Jolla, CA). Bupropion can exacerbate psoriasis, however, this is an under-recognized side effect of the medication, particularly in the United States. We report a case of bupropion-induced erythrodermic psoriasis in a 62-year-old female who was prescribed the medication for depression. Due to the common comorbidities of depression, obesity, and tobacco abuse in psoriatic patients, all for which treatment with bupropion is indicated, it is important for physicians to be aware of the potential for a life-threatening medication reaction in this patient population.

Acute Shoulder Injury.

Acute shoulder injury is commonly encountered by clinicians, surgeons, and radiologists. A comprehensive evaluation of the shoulder by the radiologist is essential to accurately relay findings that have a direct impact on acute and long-term management. In this review, imaging features of acute injuries involving the proximal humerus, glenohumeral joint, rotator cuff, tendon of the long head of the biceps brachii, and acromioclavicular joint are discussed. Modalities include ultrasound examination, conventional radiography, computed tomography scans, and MR imaging. Emphasis is placed on radiographic features that have an impact on patient management.

The human natural killer cytotoxic cell line NK-92, once armed with a murine CD16 receptor, represents a convenient cellular tool for the screening of mouse mAbs according to their ADCC potential.

To take advantage of the large number of well-characterized mouse immunoglobulins (IgGs) for the study of antibody-dependent cell-mediated cytotoxicity (ADCC) in human cells, we armed human cytotoxic lymphocytes with a mouse receptor for the Fc portion of IgG antibodies. The human ΝΚ-92 natural killer cell line was transduced with a mouse receptor gene (mCD16), which was stably expressed on the cell surface (referred to as NK-92 (mCD16) ). When tested against a B-lymphoblastoid cell line (BLCL) coated with mouse anti-CD20 IgG1, IgG2a or IgG2b monoclonal antibodies (mAbs), the newly expressed mouse Fc receptor enabled the NK-92 (mCD16) cells to kill the BLCL by ADCC. Next, using the NK-92 (mCD16) we compared mouse mAbs directed at B lineage specific CD antigens for their ability to induce ADCC against human Epstein-Barr virus- infected B lymphoblastoid (for anti-CD19, -CD20 and -CD21) or against myeloma (for anti-CD38 and -CD138) target cells. Our results demonstrated that the "NK-92 (mCD16) assay" allows convenient and sensitive discrimination of mouse mAbs for their ability to mediate ADCC in a human cellular system. In addition, our results provide examples of dissociation between opsonization and target cell killing through ADCC. These "murinized" human effector cells thus represent a convenient cellular tool for the study of ADCC.

Photocaged variants of the MunI and PvuII restriction enzymes.

Regulation of proteins by light is a new and promising strategy for the external control of biological processes. In this study, we demonstrate the ability to regulate the catalytic activity of the MunI and PvuII restriction endonucleases with light. We used two different approaches to attach a photoremovable caging compound, 2-nitrobenzyl bromide (NBB), to functionally important regions of the two enzymes. First, we covalently attached a caging molecule at the dimer interface of MunI to generate an inactive monomer. Second, we attached NBB at the DNA binding site of the single-chain variant of PvuII (scPvuII) to prevent binding and cleavage of the DNA substrate. Upon removal of the caging group by UV irradiation, nearly 50% of the catalytic activity of MunI and 80% of the catalytic activity of PvuII could be restored.

Nucleoporin 153 arrests the nuclear import of hepatitis B virus capsids in the nuclear basket.

Virtually all DNA viruses including hepatitis B viruses (HBV) replicate their genome inside the nucleus. In non-dividing cells, the genome has to pass through the nuclear pore complexes (NPCs) by the aid of nuclear transport receptors as e.g. importin beta (karyopherin). Most viruses release their genome in the cytoplasm or at the cytosolic face of the NPC, as the diameter of their capsids exceeds the size of the NPC. The DNA genome of HBV is derived from reverse transcription of an RNA pregenome. Genome maturation occurs in cytosolic capsids and progeny capsids can deliver the genome into the nucleus causing nuclear genome amplification. The karyophilic capsids are small enough to pass the NPC, but nuclear entry of capsids with an immature genome is halted in the nuclear basket on the nuclear side of the NPC, and the genome remains encapsidated. In contrast, capsids with a mature genome enter the basket and consequently liberate the genome. Investigating the difference between immature and mature capsids, we found that mature capsids had to disintegrate in order to leave the nuclear basket. The arrest of a karyophilic cargo at the nuclear pore is a rare phenomenon, which has been described for only very few cellular proteins participating in nuclear entry. We analyzed the interactions causing HBV capsid retention. By pull-down assays and partial siRNA depletion, we showed that HBV capsids directly interact with nucleoporin 153 (Nup153), an essential protein of the nuclear basket which participates in nuclear transport via importin beta. The binding sites of importin beta and capsids were shown to overlap but capsid binding was 150-fold stronger. In cellulo experiments using digitonin-permeabilized cells confirmed the interference between capsid binding and nuclear import by importin beta. Collectively, our findings describe a unique nuclear import strategy not only for viruses but for all karyophilic cargos.

Nuclear entry of hepatitis B virus capsids involves disintegration to protein dimers followed by nuclear reassociation to capsids.

Assembly and disassembly of viral capsids are essential steps in the viral life cycle. Studies on their kinetics are mostly performed in vitro, allowing application of biochemical, biophysical and visualizing techniques. In vivo kinetics are poorly understood and the transferability of the in vitro models to the cellular environment remains speculative. We analyzed capsid disassembly of the hepatitis B virus in digitonin-permeabilized cells which support nuclear capsid entry and subsequent genome release. Using gradient centrifugation, size exclusion chromatography and immune fluorescence microscopy of digitonin-permeabilized cells, we showed that capsids open and close reversibly. In the absence of RNA, capsid re-assembly slows down; the capsids remain disintegrated and enter the nucleus as protein dimers or irregular polymers. Upon the presence of cellular RNA, capsids re-assemble in the nucleus. We conclude that reversible genome release from hepatitis B virus capsids is a unique strategy different from that of other viruses, which employs irreversible capsid destruction for genome release. The results allowed us to propose a model of HBV genome release in which the unique environment of the nuclear pore favors HBV capsid disassembly reaction, while both cytoplasm and nucleus favor capsid assembly.