Development of Morphea Following Treatment with an ADA Biosimilar: A Case Report.

BACKGROUND: Tumor necrosis factor alpha (TNFα) is a pivotal cytokine involved in the pathogenesis of certain inflammatory diseases, such as rheumatoid arthritis (RA), spondyloarthropathies, and inflammatory bowel diseases. In the last two decades, TNFα inhibitors (TNFi) have revolutionized the treatment and outcome of the above disorders. However, the use of TNFi has been associated with the development of many autoimmune phenomena and paradoxical skin manifestations that may present as the same type of clinical indications for which the TNFi effectively used. Thus, they may display as arthritis, uveitis, colitis, psoriasis, and several other cutaneous clinical manifestations, among them the development of morphea, a localized scleroderma skin lesion. CASE PRESENTATION: We describe a 58-year-old woman with seronegative RA, refractory to methotrexate, who was treated with ABP-501 (Hefiya), an adalimumab (ADA) biosimilar and developed an oval-shaped, deep skin lesion of approximately 3.5cm in size, affecting the left part of her back compatible with morphea 3 months after the initiation of therapy. ADA biosimilar was discontinued and two months later, she had substantial skin improvement. CONCLUSION: This is the first report of morphea manifestation during TNFi biosimilar since the patient had no other trigger factors for morphea development like trauma and infections. Physicians dealing with patients treated with TNFi biosimilars should be aware of paradoxical skin reactions, among them morphea; thus, close monitoring, a minute and careful clinical examination, and a follow- up check are required.

Cutaneous immune-related phenomena in patients with inflammatory arthritides treated with biological therapies: Clinical and pathophysiological considerations.

In recent years, identifying the pathophysiologic mechanisms underlying autoimmune arthritides and systematic diseases has led to the use of biological drugs. The primary targets of those biological therapies are cytokines, B cells, and co-stimulation molecules. So far, these targeted therapies have shown good clinical improvement and an acceptable toxicity profile. However, by blocking components of an intact immune system, autoimmune phenomena and paradoxical inflammation have emerged, and among them many cutaneous immune-related adverse events (irAEs). In this article, we review the current state of knowledge on the clinical features and mechanisms of specific cutaneous irAEs observed during treatment with biological therapies. Among those, psoriatic skin lesions are the most commonly observed. Herein, we also report new cases of cutaneous irAEs recently seen in our clinic to help physicians treating inflammatory arthritides recognize cutaneous irAEs early and better manage patients receiving biologic therapies.

Can Sulfonylureas for Agricultural Use Cause Diabetes? A Report of Three Cases.

Sulfonylureas (SUs) are commonly used as herbicides. Many farmers and other professionals use SUs for cereal, strawberry, and grape crops. This study examines the possible association between exposure to SUs herbicides and the risk of developing type 2 diabetes (T2D). The study presents three cases of unrelated agronomists who had used SUs for more than three decades and developed T2D. The objective was to investigate the association between occupational dermal and inhalation exposure to herbicides and T2D. Further studies with a larger sample size are needed to determine the association and to help develop prevention strategies.

Flagellate dermatitis in a patient with testicular germ cell neoplasia on bleomycin.

Bleomycin, an antineoplastic antibiotic that inhibits DNA synthesis, is used to treat various malignant tumors such as Hodgkin's lymphoma, squamous cell carcinoma, and germ cell tumors. Flagellate erythema is a rare rash with a linear pattern that has been observed in association with bleomycin treatment. Herein, we present a 43-year-old patient with metastatic testicular cell neoplasms who developed a whiplash rash during treatment with a chemotherapy regimen that included bleomycin. A typical case of bleomycin-related flagellate dermatitis has been diagnosed and the main features of this characteristic adverse drug event are briefly discussed.

Screening for insulin-like growth factor-I receptor mutations in patients with Silver-Russell syndrome.

Individuals with a deletion of 15q26.1-->qter which contains the insulin-like growth factor-I (IGF-I) receptor gene exhibit phenotypical similarities to patients with Silver-Russell syndrome (SRS) who represent a group of short children affected by pre- and postnatal growth failure and several dysmorphic features. The genetic basis of SRS is presumably heterogeneous. The IGF-I receptor gene is a good SRS candidate gene because the biological effects of the major growth factors IGF-I and -II are transmitted through the IGF-I receptor during pre- and postnatal growth. All 12 patients studied exhibited the classical SRS phenotype with low birth weight, connatal macrocephaly, typical facial features and short stature at presentation. Klinodactyly of the fifth finger was found in ten patients, and skeletal asymmetry in seven. Chromosomal analysis gave normal results. Uniparental disomy of chromosome 7 was excluded. After reverse transcription of RNA, 19 overlapping cDNA fragments encompassing the whole IGF-I receptor coding sequence were PCR-amplified and screened for mutations by single strand conformation analysis (SSCP). In eight of 12 patients studied, we detected four SSCP polymorphisms which were directly sequenced. All single base exchanges (C948A, C2343T, G3174A and G3915A) were silent variants of the IGF-I receptor gene, two of which were also present in control individuals. In conclusion, for the first time, the complete coding region of the IGF-I receptor gene was screened for mutations in patients with SRS. Our data do not support the suggestion that the IGF-I receptor is frequently involved in the pathogenesis of SRS.