Clinical profile, treatment and outcome of children with xeroderma pigmentosum at Muhimbili National Hospital, Dar es salaam, Tanzania

Abstract

Introduction: Xeroderma Pigmentosum (XP) is a rare hereditary disease of defective deoxyribonucleic acid repair defined by extreme sensitivity to sunlight, resulting in sunburn, pigment changes in the skin and a greatly elevated incidence of skin cancers. Estimated prevalence is between 1 to 50 per million population. Mortality mainly occurred secondary to malignancy from 2nd decade of life. Objectives: To determine Clinical profile, treatment and outcome of children with xeroderma pigmentosum at Muhimbili National Hospital, Dar es salaam, Tanzania from June 2011 to December 2020. Methods: A retrospective cohort study with a longitudinal follow up of the pediatric patients with XP who attended either the pediatric oncology unit or dermatology clinic at MNH. A total of 100 files and database records of registered patients with XP were extracted using a structured data collection tool. All patients with available contact information identified in their case notes or database were contacted and consented for a short mobile interview. Data analysis was done using Statistical Package for the Social Sciences version 23. Patients’ socio-demographical and clinical profiles were described using frequencies and percentages for categorical variables, for continuous variables means and standard deviations was calculated. Kaplan-Meier survival analysis was used to determine the overall survival rate of XP patients. Independent predictors of XP patients’ survival were assessed in adjusted Cox regression model. The risk of mortality was presented using hazard ratio and 95% confidence interval and P-value less than 0.05 were considered as significant. Results: Of the 100 enrolled patients, half were male. The mean age was 5.4 ± 4.1 years. Thirty six percent (36%) had family history of XP while only 8% had history of consanguinity. The mean age at first symptom presentation was 1.1±SD 1.8 years. Cutaneous manifestation was found in 99% of the patients, in which 41% had cutaneous squamous cell carcinoma (cSCC). Ninety three percent had ocular findings in which 25% had developed ocular squamous cell carcinoma. Only 14% of XP patients had documented oral Squamous cell carcinoma. Surgical therapy, chemotherapy and radiotherapy were received by 54%, 31% and 25% respectively. At the end of the study follow up period, 39% of enrolled patients were alive and still on active follow up, while 35% of patients had been lost to follow up and death had been confirmed among 26%. The median survival was 14.1 years (IQR= 11.7 – 17.2). Estimated overall survival rate was 90%, 64% and 46% at 5, 10 and 15 years respectively. Those with cSCC had lower survival rate, 87% and 55% at 5 and 10 years respectively. Cutaneous squamous cell carcinoma was found to be a strong predictor of mortality among patients with XP (HR 2.8, 95% CI 1.0-7.3, P= 0.02). Conclusion: Xeroderma Pigmentosum is an inherited disease which affects male and female equally. Skin and eyes are the most affected organs and can be protected by using protective measures such as sun cream and hats. Survival of the patients with XP is progressively decreasing from 90%, 64% and 46% at 5, 10 and 15 years respectively. Those XP patients with cSCC had lower survival rate compared to those with no cSCC which was found to an only predictor of mortality in patients with XP. We recommend early identification of patients with XP and initiation of preventive measures to reduce morbidity and mortality. This can be achieved by raising awareness among health care workers and the community, and by educating parents of patients with XP regarding the prevention of cSCC.