Determinants of Keloid Recurrence in African Patients at Kenyatta National Hospital

Abstract

Background: Keloids are fibro-proliferative disorders of the skin resulting in excessive tissue overgrowth usually due to minor tissue injury. Keloids are attributed to abnormal wound healing with an exaggerated inflammatory phase and a poorly controlled proliferative phase. Patients with keloids have been shown to be heterogeneous in clinical, pathological and genetic make ups. There are many modalities of treating keloids. However, all are associated with high recurrence rates. Factors that influence keloid recurrence either locally or globally have not been well demonstrated. This study therefore sought to determine factors that are associated with keloid severity and recurrence among patient’s cohorts in KNH. A control of patients with no keloids nor family history of keloids were also followed up in the study. Rationale for the study: Keloid disease is a common medical condition. It results in both psychological and physical stress to patients. The recurrence rates are high with studies quoting recurrence of between 10 and 70%. To the best of my knowledge, no studies had been done to determine factors that influence recurrence in our population. Understanding factors that influence keloid recurrence would aid in keloid management by enabling patients to have an informed mind on the chances of recurrence as well as allowing the physicians to start on second line management early in cases where recurrences are likely to be high. Objective: To determine the genetic, clinical, inflammatory and histo-pathological factors that influence keloid recurrence. Study Design: A Case control observational study of patients presenting with keloids at the KNH. Setting: Kenyatta National Hospital, Nairobi, Kenya. Ethical considerations: This study was approved by the UON/KNH ethics and research committee. Confidentiality ran supreme during the course of the study. Informed consent was sought from all patients who participated in the study. Methodology: Patients with keloids and a control with no keloids after consenting were recruited for the study. Inclusion in the study was limited to patients whose keloids could be excised and closed primarily. Excluded from the study were patients with extensive keloids that could not be closed primarily after excision or those with chronic medical conditions. Targeted history and physical examination on the causation of keloids and clinical presentation was taken. Patients were managed by surgical excision followed by superficial radiotherapy. Specimens from the excised keloids were analyzed for lymphocytes, macrophages, mast cells, fibroblasts as well as extracellular matrix density. Immuno-histochemical studies were done on selected slides to determine the presence of mast cells, fibroblasts and myofibroblasts. Mesenchymal stem cells were assessed by flow cytometry studies. The extra-cellular matrix was analyzed for vascularity and the collagen bundles densities. Blood samples were taken for blood groups, HLA sub-types and inflammatory cytokines. Post-operatively, patients were followed up to a minimum of one year and any keloid recurrences were noted. Data and Statistical Analysis: All the information was collected in a pre-tested questionnaire. A student T-test was used to compare means and a Chi-square was used to test variance from the mean. Pearson’s correlation co-efficient (r) was used to measure the strength of the association between the various variables and keloid recurrence. Analysis of variance (ANOVA) was done to determine variance in the various groups. Bonferroni correction was done to determine the significance of the statistical differences. Multiple regression analysis was done to determine the strength of variables in keloid recurrence. Descriptive analysis, cross tabulation and comparison of means were used in analysis. Odds ratios and mean difference were used to measure association and 95% confidence intervals to measure significance. STATA/SE statistics/data analysis version 10 software was used for analysis. Results: A total of 90 patients and a control of 59 patients were recruited for the study. The male to female ratio for the keloid and control patients was 1:2. The age ranges for the keloid patients was 15 to 65 years with a mean age of 29.5 and a median age group of 20-25 years. Familial keloids contributed to 53% of keloids with sporadic keloids at 47 %. Majority of the keloids were due to trauma (63.5%). Ear keloids were the most common accounting for 43% of the keloids. Male patients had a significantly higher recurrence rate of 31% compared to the female patients at 12%. The recurrence rates were higher in the familial keloids at 26.9 % compared to the sporadic keloids at 18.5%. There was no statistically significant difference in the surface area of patients who had keloid recurrence and those with no recurrence. Keloid patients with blood group A were more prone to recurrence compared to the other blood groups. Patients with keloids had a significantly higher positive alleles of DQA*01, DQB1*05, DQB1*06 and DRB1*15. Comparison between patients who had keloid recurrence and those who did not revealed DQB1*06 to be significantly elevated in patients with keloids recurrence (p-value <0.05). Keloid specimens had significantly higher MSC counts compared to the normal skin. Further Keloid specimens had a higher ratio of MSC compared to the normal skin. Histological parameters revealed that high macrophages, lymphocytes and fibroblast counts were significantly associated with keloid recurrence. Conclusion: This study demonstrates that keloid recurrence is influenced by many factors including patients’ sex, history, clinical presentation, keloid histology and HLA subtypes. There is need to identify these factors in patients that could influence keloid recurrence. Patients with increased likelihood of keloid recurrence should be identified through proper history and physical examination followed by relevant laboratory tests They should be managed by either non - surgical methods or be given a higher dose of post excision superficial radiotherapy. They could further be monitored closely so as to intervene as soon as any sign of recurrence occurs