Paradoxical and bimodal immune-mediated dermatological side effects of TNF-α inhibitors: A comprehensive review.

INTRODUCTION: Due to the increasing prevalence of immune-mediated diseases such as psoriasis, lichen planus, rheumatoid arthritis and inflammatory bowel disease, dermatologists have turned to new biologic drugs known as DMARDs (disease-modifying anti-rheumatic drugs) in recent years. AREAS COVERED: In this study, we evaluate the immune-mediated dermatological side effects of DMARDS by reviewing and analyzing previous peer-reviewed research on the effects of TNF-α inhibitors in the treatment of skin diseases, as well as adverse effects of these drugs and some of the main causes of these effects. EXPERT OPINION: DMARDs are very effective in improving control of the above diseases. TNF-α inhibitors are an important group of DMARDs that are widely used. The paradoxical adverse events (PAEs) associated with the use of TNF-α inhibitors are divided into three categories: true paradoxical, borderline paradoxical, and non-paradoxical. True PAEs include conditions for which TNF-α inhibitors are approved for treatment. Borderline PAEs are considered to occur with this class of drugs for which there is no definite approval but for which there is sufficient evidence. Although these events are rare, early recognition of the accused drug and appropriate decision-making may prevent progression of complications and irreversible side effects.

Wells syndrome following vaccination: A pediatric case with positive patch test to gelatin.

We report a 12-month-old boy with a skin eruption that developed 15 days after receiving the measles, mumps, rubella (MMR), pneumococcal, and meningococcal vaccines, consistent with the diagnosis of Wells syndrome. Patch testing showed a positive reaction to gelatin, which is used as a stabilizer for both live and inactivated vaccines. Gelatin was only present in the MMR vaccine.

Treatment of Eosinophilic Annular Erythema: Retrospective multicenter study and literature review.

BACKGROUND: Eosinophilic annular erythema (EAE) is a rare eosinophil-related skin disease which typically manifests with annular erythematous plaques and severe pruritus. Besides the diagnosis, the treatment of EAE is challenging since relevant published data are sparse. METHODS: The aim of this study was to assess the underlying diseases, treatments and outcomes of patients with EAE. To this end, we conducted a retrospective multicenter study and a systematic review of the MEDLINE database. RESULTS: We included 18 patients with EAE followed in 8 centers. The MEDLINE database search yielded 37 relevant publications reporting 55 cases of EAE with 106 treatment sequences. The most common and efficient treatments included topical or systemic corticosteroids, hydroxychloroquine and dapsone. In refractory patients, a combination of systemic corticosteroids with hydroxychloroquine was associated with 88% of complete clinical response. DISCUSSION: To improve the management of EAE patients, we discuss the following treatment strategy: in topical steroid-resistant patients, hydroxychloroquine can be given as first-line systemic treatment. Dapsone, hydroxychloroquine or systemic corticosteroids are second-line options to consider. Last, monoclonal antibodies or JAK inhibitors targeting type 2 inflammation could represent promising last-resort options in refractory patients.

[A CASE OF ALLERGIC RHINITIS WHO HAS DEVELOPED EOSINOPHILIC PNEUMONIA, FOLLOWED BY EOSINOPHILIC CELLULITIS].

A-68-year-old man, who has allergic rhinitis with peripheral blood eosinophilia, hospitalized because of fever of unknown origin in May 2020. Five days after antibiotics were given, itchy exanthema occurred, followed by gland glass opacity on both lungs with bilateral pleural effusions. Since acute respiratory failure developed, bronchoscopy was hard to carry out. However, this case was considered acute eosinophilic pneumonia induced by antibiotics, based on radiological findings and laboratory data. Therefore, steroid pulse therapy using intravenous administration of methylprednisolone started, and this therapy was effective. Since these chest shadows and hypoxia were disappeared in two weeks, the amount of steroid was gradually reduced, however, eosinophilic pneumonia recurred once during this course. After discharge in June 2020, this patient came to the outpatient department. When oral administration of prednisolone was decreased less than 2.5mg/day, redness and swelling with slight itch were appeared in the left forearm in September 2020. Histological findings from shin biopsy showed that eosinophils excessively invade to the dermis without angiitis. Although flame figure was not observed in the specimen, we considered that this case has developed eosinophilic cellulitis, based on the clinical manifestation and pathological findings. When prednisolone was increased to 30mg/day, these symptoms were improved, and then prednisolone was gradually reduced. After that, recurrences of these diseases did not occur during the observation period. This case may be diagnosed as hypereosinophilic syndrome since eosinophilic pneumonia and eosinophilic cellulitis caused continuously by recruitment of eosinophils to lung and skin.

Eosinophilic cellulitis successfully treated with Methotrexate.

Eosinophilic cellulitis is a rare inflammatory skin disease of unknown aetiology, first described by George Wells in 1971 as a recurrent granulomatous dermatitis with eosinophilia. It is typically characterised by recurrent pruritic erythematous plaques, vesicles or bullae usually involving the extremities and trunk. Many cases of eosinophilic cellulitis are difficult to treat and traditionally require long course of oral steroids, resulting in steroid side effects. This case adds to the literature in that we report the use of methotrexate to treat eosinophilic cellulitis, as a safe and efficacious therapeutic alternative.

A review of cutaneous hypersensitivity reactions in infants: From common to concerning.

Cutaneous hypersensitivity reactions in infants present in a variety of patterns. These skin eruptions can be dramatic, causing alarm in parents and medical personnel. Many of these syndromes have overlapping features, which adds to the confusion and uncertainty regarding diagnosis and management. This review discusses the spectrum of hypersensitivity responses with a focus on their presentation in infants. The clinical findings, pathophysiology, histopathology, management, and complications of these conditions will be reviewed.

Pediatric Wells syndrome (eosinophilic cellulitis) after vaccination: A case report and review of the literature.

A 4-year-old boy presented with erythematous vesicular plaques, ulceration, edema, and pruritus on the left foot and ankle 10 days after receiving the tetanus, diphtheria, pertussis, and polio; measles, mumps, rubella, and varicella; and hepatitis A/B vaccines. Biopsy showed eosinophilic infiltrates and flame figures, suggesting Wells syndrome. Patch testing showed a 1+ reaction to neomycin and aluminum hydroxide, with a recall reaction of Wells syndrome of the feet bilaterally. We report a rare case of pediatric Wells syndrome triggered by nonthimerosal vaccine components confirmed by patch testing.

[Wells syndrome mimicking facial cellulitis: Three cases]. / Syndrome de Wells mimant une cellulite infectieuse de la face : trois observations.

BACKGROUND: Wells syndrome, or eosinophilic cellulitis, is an uncommon inflammatory dermatosis of unknown etiology that is characterized by clinical features of pruritic cellulitis-like plaques on the extremities and a histological picture of eosinophilic infiltrate of the dermis with "flame figures". PATIENTS AND METHODS: Herein, we report three cases of idiopathic Wells syndrome masquerading as bacterial facial cellulitis. Under treatment with oral prednisone and/or combined therapy with levocetirizine and hydroxyzine, all patients showed a dramatic improvement of their skin lesions. DISCUSSION: These cases highlight the need to consider Wells syndrome in the differential diagnosis when evaluating a patient with facial cellulitis that does not respond to an initial antimicrobial regimen. In addition, our cases suggest that combined therapy with levocetirizine and hydroxyzine may be successfully used as first-line therapy or to prevent relapse after discontinuation of corticosteroid treatment.

[Eosinophilic cellulitis: About a new pediatric case]. / Cellulite à éosinophile : à propos d'un nouveau cas pédiatrique.

Wells' syndrome or "eosinophilic cellulitis" is characterized by clinical features of cellulitis and histological pictures of eosinophils infiltrate of the dermis with some « flame ¼ figures. This is a very rare disease in the pediatric age. We report the case of a 14-month-old boy, presented with two farms painful nodular brownish lesions in the thigh and back of the foot as well as multiple erythematous papular and vesicular lesions on the forehead, cheeks, limbs and trunk. Biological analysis and histological examination confirmed the diagnosis of Wells' syndrome. The outcome was favorable with dermocorticoid.

Eosinophilic cellulitis (Wells' syndrome) caused by a temporary henna tattoo.

Eosinophilic cellulitis (Wells' syndrome) is an uncommon condition of unknown etiology. Wells' syndrome is usually seen in adulthood but very rare in childhood. Although pathogenesis of the disease is not very clear, it is a hypersensitivity reaction developing against a variety of exogenous and endogenous antigenic stimuli. Paraphenylenediamine is a strong allergen frequently used as a temporary henna tattoo, which makes the color darker. Here, a 9-year-old male patient with Wells' syndrome is presented, which developed following a temporary henna tattoo and shown by the patch test sensitivity to paraphenylenediamine.

Eosinophilic Dermatosis of Hematologic Malignancy: Emerging Evidence for the Role of Insect Bites-A Retrospective Clinico-Pathological Study of 35 Cases.

Background/Objectives: Eosinophilic dermatosis of hematologic malignancy (EDHM) is a rare cutaneous disorder associated with various hematologic malignancies, most commonly chronic lymphocytic leukemia. Detailed clinicopathologic studies of EDHM are lacking and the pathogenesis remains enigmatic. Initially thought to be a hypersensitivity reaction to insect stings, subsequent reports have challenged this understanding. The prognostic implications of EDHM remain unclear. Methods: A retrospective clinicopathologic study was performed on patients diagnosed with EDHM. Hematologic and dermatologic data were reviewed. Histologic specimens were re-evaluated and lesions were classified into acute/subacute, fully developed, and chronic/regressing. Results: The study included 35 patients. In 80% of these patients, EDHM was diagnosed after the hematologic disorder. Approximately 45% of the cohort experienced hematologic disease progression or relapse, while 65% required therapeutic intervention during the course of their hematologic disease. In total, 15/19 CLL patients had non-mutated IgHV, a marker of a more aggressive hematologic disease course. Dermatologic lesion morphology was heterogeneous, with most lesions occurring on exposed areas, and a significant 94% of patients demonstrated lesion seasonality. Histopathologic findings were consistent with features typically associated with insect bites. In addition, examination of lesions at different chronological stages revealed substantial similarities with Wells syndrome. Conclusions: Our findings support the potential role of insect bites in triggering EDHM in the context of adaptive immune dysfunction. EDHM may be associated with a more aggressive disease course or may be a marker of disease progression. The observed co-occurrence of features typical of Wells syndrome in EDHM patients suggests that these conditions are part of a spectrum of disorders that vary in clinical expression.

Clinical Entity Mimicking Infectious Cellulitis: Eosinophilic Cellulitis (Wells' Syndrome).

Eosinophilic cellulitis (EC) is a skin disease characterized by pruritic, non-purulent, erythematous plaques and histologically by edema and eosinophil infiltration in the dermis. The etiopathogenesis of the disease is not fully elucidated. It differs from infectious cellulitis by being unresponsive to antibiotics and recurring. This case report presents a late-diagnosed case of EC in a patient who did not respond to long-term and broad-spectrum antibiotics. This case underscores the importance of skin biopsy and histopathological diagnosis in patients with recurrent, non-responsive, antibiotic-resistant, and cellulitis-like clinical features resembling infectious cellulitis; "eosinophilic cellulitis" should be considered in the differential diagnosis.

Revolutionizing Dupilumab Treatment in Refractory Eosinophilic Cellulitis: A Case Report and Comprehensive Literature Review.

Eosinophilic cellulitis (EC) or Wells' syndrome, characterized by its rarity and diverse clinical presentations, presents substantial challenges in diagnosis and treatment. This case study details the challenging journey of a 48-year-old woman with non-specific skin lesions, showcasing the persistence of dermatitis despite exhaustive attempts at various interventions outlined in the literature. In the absence of a consensus on optimal management for EC, this study introduces a transformative solution through the utilization of dupilumab, a monoclonal antibody targeting interleukin-4/interleukin-13. The patient experienced marked improvement and resolution of dermatitis following dupilumab treatment alone, highlighting the efficacy of this targeted immunomodulatory approach in cases refractory to traditional therapies. This pioneering case underscores the significance of exploring innovative treatments and suggests dupilumab as a potential breakthrough therapeutic option in addressing EC refractory to standard medical management.

[Flame figures-eosinophils setting the skin on fire]. / Flammenfiguren ­ Eosinophile, die die Haut in Brand setzen.

A 50-year-old female farmer was initially diagnosed with generalized granuloma annulare and treated with local steroids and ultraviolet (UV) light therapy for 10 years, albeit without success. A histopathological examination in our clinic changed the diagnosis to Wells' syndrome, based on the typical findings of eosinophilic cellulitis together with flame figures. A systemic approach with pulse steroid therapy resulted in complete remission of pruritus and skin manifestations. This case demonstrates successful treatment of a patient with eosinophilic cellulitis.