Multiple Cytokines Elevated in Patients with Keloids: Is It an Indication of Auto-Inflammatory Disease?

BACKGROUND: Inflammation seems to play a major role in the pathophysiology of keloids. However, the role of cytokines in keloid pathophysiology has not been fully evaluated with only a few cytokines studied. We undertook this study to compare various cytokines in patients with keloids and a control group of patients without keloids nor family history of keloids so as to determine which cytokines are elevated and could thus be critical in keloid formation. METHODS: This was a cross-sectional study of patients with keloids and a control group of those without. Patients in both groups were matched for age, sex and body mass index. Their plasma was analyzed for both inflammatory and anti-inflammatory cytokines using the Bio-flex ElisaTM method. Comparisons of cytokines means in both groups were done using Student's t-test. RESULTS: A total of 84 participants with 42 participants in each group were followed during the study. Male to female ratio was 1:2. Age ranges were similar with a mean of 29.6 years. A total of 28 cytokines were assayed. Statistically significant differences were noted in 15 of the 28 cytokines assayed with 11 being elevated more in keloid patients with only four in the non-keloid forming group. Among elevated cytokines in keloid patients were granulocyte colony-stimulating factors, granulocyte-monocyte-colony-stimulating factors, interleukins 4, 6 and 13. CONCLUSION: Patients with keloids have significantly higher cytokines compared with non-keloid forming patients. This finding suggests that keloid formation could be influenced by multiple inflammatory cytokines, an indication that the patient's immune system could play a role in keloid formation akin to auto-inflammatory disease.

Does Keloid Histology Influence Recurrence?

ABSTRACT: Keloids are fibroproliferative disorders characterized by high recurrence rates, with few factors known to influence the same. We conducted a study to determine whether keloid histology influences recurrence. This was a prospective longitudinal study to determine whether histopathological parameters of keloid influence recurrence. Patients with keloids managed by surgical excision were followed up at Kenyatta National Hospital between August 2018 and July 2020. The excised keloids were processed for histology using hematoxylin,/eosin, Masson, and trichrome stains. The slides were analyzed for inflammatory cells, fibroblasts, and capillary density using the hot spot technique and correlated to keloid recurrence. Postoperative follow-up was for a minimum of 1 year. A total of 90 patients with 104 keloids were recruited in the study. Overall keloid recurrence rate was 28.6%. There was a correlation between the absolute count of more than 50 per High power field of lymphocytes, fibroblasts, and macrophages with recurrence of the disease. The sensitivity and specificity for the above parameters were lymphocytes 48% and 81%, macrophages 57% and 83%, mast cells 32% and 33%, and fibroblasts 41% and 91%, respectively. There was no correlation between mast cells and vascularity status with recurrence. Routine histology should, therefore, be performed to determine these parameters. Close monitoring and second-line therapy should be considered for patients with elevated macrophages and/or lymphocytes so as to reduce the risk of recurrence.

Keloid pathophysiology: fibroblast or inflammatory disorders?

BACKGROUND: Keloids are defined as a benign dermal fibroproliferative disorder with no malignant potential. They tend to occur following trivial trauma or any form of trauma in genetically predisposed individuals. Keloids are known to grow beyond the margins of the wound and are common in certain body parts. The pathophysiology of keloid remains unclear, and fibroblasts have been presumed to be the main cells involved in keloid formation. Understanding the mechanism(s) of keloid formation could be critical in the identification of novel therapeutic regimen for the treatment of the keloids. OBJECTIVE: To review the pertinent literature and provide updated information on keloid pathophysiology. DATA SOURCE: A Medline PubMed literature search was performed for relevant publications. RESULTS: A total of 66 publications were retrieved, with relevant publications on the etiology and pathogenesis as well as experimental studies on keloids. All articles were critically analyzed, and all the findings were edited and summarized. CONCLUSION: There is still no consensus as on what is the main driving cell to keloid formation. One may, however, hypothesize that keloid formation could be a result of an abnormal response to tissue injury, hence resulting in an exaggerated inflammatory state characterized by entry of excessive inflammatory cells into the wound, including macrophages, lymphocytes, and mast cells. These cells seem to release cytokines including transforming growth factor ß1 that stimulate fibroblasts to synthesize excess collagen, which is a hallmark of keloid disease.