A case of trichodysplasia spinulosa related to ruxolitinib treated successfully with oral acitretin.

Trichodysplasia spinulosa (TS) is a rare disease that affects immunocompromised patients, characterized by hair-like growths caused by TS-associated polyomavirus infection. Little is known about specific immunosuppressive drugs that can precipitate the condition. We report a case of TS presenting after initiating the oral Janus-associated kinase inhibitor (JAKi) ruxolitinib. A 67-year-old female with a history of allogeneic bone marrow transplant requiring immunosuppression with tacrolimus, prednisone and, more recently, ruxolitinib 5 mg twice daily due to Graft versus Host Disease presented to the clinic with a facial rash. The clinical and histopathological findings in the setting of immunosuppression were consistent with TS. Initial treatments were ineffective, but oral acitretin showed significant improvement after 3 months. Due to the close temporal relationship between the initiation of ruxolitinib and the development of TS, this case suggests that JAKis may contribute to TS development by suppressing the JAK-signal transducer and activator of the transcription pathway's antiviral functions.

A Review of the Immunologic Pathways Involved in Bullous Pemphigoid and Novel Therapeutic Targets.

Bullous pemphigoid (BP) is a rare, chronic antibody-mediated autoimmune blistering disease primarily affecting the elderly, with an age of onset over 60. Current treatment options are limited and involve the use of corticosteroids and immunosuppressants, but their long-term use is associated with significant morbidity and mortality. In Japan, human intravenous immunoglobin is approved for the treatment of corticosteroid-refractory BP. However, no treatment option is approved by the Food and Drug Administration for the management of BP. Therefore, developing effective therapies free of debilitating side effects is imperative. In this review, we summarize the main immunologic pathways involved in the pathogenesis of BP, with an emphasis on the role of eosinophils, immunoglobulins, cytokines such as the interleukin (IL)-4 and IL-5, and complements. We further discuss the latest advances with novel therapeutic targets tested for the management of BP. Ongoing efforts are needed to run well-designed controlled trials and test the efficacy and safety of investigational drugs while providing much-needed access to these medications for refractory patients who will not otherwise be able to afford them as off-label prescriptions.

Development of a working core outcome set for cutaneous lupus erythematosus: a practical approach to an urgent unmet need.

OBJECTIVE: The lack of standardised outcomes and outcome measures for cutaneous lupus erythematosus (CLE) represents a substantial barrier to clinical trial design, comparative analysis and approval of novel investigative treatments. We aimed to develop a working core outcome set (COS) for CLE randomised controlled trials and longitudinal observational studies. METHODS: We conducted a multistage literature review of CLE and SLE studies to generate candidate domains and outcome measures. Domains were narrowed to a working core domain set. Outcome measures for core domains were identified and examined. RESULTS: Proposed core domains include skin-specific disease activity and damage, investigator global assessment (IGA) of disease activity, symptoms (encompassing itch, pain and photosensitivity), health-related quality of life (HRQoL) and patient global assessment (PtGA) of disease activity. Recommended physician-reported outcome measures include the Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and Cutaneous Lupus Activity IGA (CLA-IGA). For the domains of symptoms, HRQoL and PtGA of disease activity, we were unable to recommend one clearly superior instrument. CONCLUSION: This work represents a starting point for further refinement pending formal consensus activities and more rigorous evaluations of outcome measure quality. In the interim, the proposed working COS can serve as a much-needed guide for upcoming CLE clinical trials.

Fluorescence microscopy for the evaluation of elastic tissue patterns within fibrous proliferations of the skin on hematoxylin-eosin-stained slides.

BACKGROUND: Diagnosis of fibrous tumors can be challenging and expensive due to the use of special stains. OBJECTIVE: Determine the usefulness of fluorescence microscopy in the evaluation of elastic tissue patterns on hematoxylin-eosin-stained slides. METHODS: In total, 228 slides representing different fibrous tumors were evaluated for their elastic tissue patterns by fluorescence microscopy, and sensitivity and specificity were determined for relevant comparisons. RESULTS: Fluorescence microscopy was found to be useful, especially for distinguishing dermatofibroma from dermatofibrosarcoma protuberans and dermatomyofibroma from other fibrous tumors. LIMITATIONS: In some cases, excessive background staining made patterns difficult to interpret. CONCLUSION: Evaluation of elastic tissue patterns by fluorescence microscopy in fibrous tumors is a cheap and efficient means to further delineate these often challenging tumors.

Candidate drug replacements for quinacrine in cutaneous lupus erythematosus.

Cutaneous lupus erythematosus (CLE) is a disfiguring and potentially disabling disease that causes significant morbidity in patients. Antimalarials are an important class of medication used to treat this disease and have been the first-line systemic therapy since the 1950s. Quinacrine, in particular, is used as an adjuvant therapy to other antimalarials for improved control of CLE. Quinacrine is currently unavailable in the USA, which has taken away an important component of the treatment regimen of patients with CLE. This paper reviews the evidence of available local and systemic therapies in order to assist providers in choosing alternative treatments for patients who previously benefited from quinacrine therapy.

An Update on the Pathogenesis of Cutaneous Lupus Erythematosus and Its Role in Clinical Practice.

PURPOSE OF REVIEW: Understanding the pathogenesis of cutaneous lupus erythematosus (CLE) is an important step in developing new medications and providing effective treatment to patients. This review focuses on novel research within CLE pathogenesis, as well as some of the medications being developed based on this knowledge. RECENT FINDINGS: The subtle differences between systemic lupus erythematosus (SLE) and CLE pathogenesis are highlighted by differences in the circulating immune cells found in each disease, as well as the specific pathways activated by ultraviolet light. Plasmacytoid dendritic cells and the related type I interferon pathway are major components of CLE pathogenesis, and as such, therapies targeting components of this pathway have been successful in recent clinical trials. B cell-depleting therapies have shown success in SLE; however, their role in CLE is less clear. Understanding the differences between these manifestations of lupus allows for the development of therapies that are more effective in skin-specific disease. Discovering key pathways in CLE pathogenesis is critical for understanding the clinical features of the disease and ultimately developing new and effective therapies.

Expert Perspective: An Evidence-Based Approach to Refractory Cutaneous Lupus Erythematosus.

Cutaneous lupus erythematosus (CLE) is a chronic autoimmune disease that can present with a variety of skin manifestations and have a dramatic effect on a patient's quality of life. Effective treatment options for this disease are limited, and the efficacy of these treatments is often supported by low levels of evidence. This makes the treatment of refractory disease especially challenging, as it is difficult to achieve a consensus on the appropriate progression of treatment beyond first- and second-line treatment options. The treatment of refractory CLE often involves some degree of immunosuppression, which carries some risk for patients and requires a thoughtful approach to the selection of medications. Some treatments that have proven to be effective in systemic disease may not be as effective in cutaneous disease, making it difficult to extrapolate from the available evidence on systemic lupus erythematosus (SLE). Ultimately, the increased use of objective skin measurements in SLE clinical trials is necessary to understand drug efficacy in CLE and develop new treatments for this challenging disease. Here, we provide clinical examples of the challenges involved in treating refractory CLE, examine the evidence currently available for treatment options, and provide an algorithmic approach to the treatment of refractory disease based on this evidence. Novel therapies under development for CLE are also discussed, as they may soon be part of the accepted treatment regimen for refractory CLE.

Response letter to 'chronic cutaneous lupus erythematosus induced by 5-fluorouracil'.

The diagnosis of cutaneous lupus erythematosus (CLE) presents a challenge due to its heterogeneous nature. This is especially true in cases of discoid lupus erythematosus (DLE), which in the past has not had clearly defined diagnostic criteria. The recent development of classification criteria for DLE has made its diagnosis more straightforward; however, some cases previously called DLE must now be reclassified.

Cutaneous lupus erythematosus induced by drugs - novel insights.

Introduction: There is a growing list of drugs implicated in inducing both subacute and chronic forms of cutaneous lupus erythematosus. It is important to recognize these drugs in order to quickly treat patients with drug induced disease.Areas covered: This paper reviews the current literature describing drugs implicated in causing cutaneous lupus erythematosus. A Pubmed search was used to compile a list of medications implicated up to August 2019. It reviews new classes of drugs identified as causing cutaneous lupus erythematosus, the pathophysiology of the disease process, and current recommendations for treatment of the disease.Expert opinion: Many drugs have been identified as inducing lupus, and many more continue to be described in new reports. Further research is needed to understand this phenomenon, which will aid in the diagnosis and treatment of affected patients.

Malignant fibrous histiocytoma: Database review suggests a favorable prognosis in the head and neck.

OBJECTIVE: The malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of the head and neck. Currently, most of the data on this tumor relies on small retrospective studies. The objective of this study is to use the Surveillance, Epidemiology, and End Results (SEER) database to compare characteristics of this tumor based on location to better understand its prognosis in the head and neck region. This article represents the largest study analyzing prognosis of this tumor in the head and neck to date. STUDY DESIGN: Retrospective analysis of SEER database. METHODS: Using the SEER database, 395 patients with MFH of the head and neck were compared with 3,968 patients with MFH of the trunk and extremities. Disease-specific survival was carried out comparing these two cohorts, as well as univariate and multivariate analysis to determine hazard ratios. RESULTS: Head and neck MFH had a significantly higher disease-specific survival compared with trunk and extremity disease. However, head and neck tumors were more frequently a smaller size (P < .0001) and lower grade (P < .0001). Larger tumors and grade III and IV tumors conferred a worse prognosis (P < .0001). CONCLUSION: Head and neck malignant fibrous histiocytoma presents at a smaller size and lower grade, likely due to earlier presentation in this region. Because of this, head and neck malignant fibrous histiocytoma represents a more favorable survival prognosis compared with trunk and extremity disease. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:885-888, 2018.