Sickle Cell Disease.

Background: Sickle cell disease (SCD) is among the most frequent hereditary disorders globally and its prevalence in Europe is increasing due to migration movements. Summary: The basic pathophysiological event of SCD is polymerization of deoxygenated sickle hemoglobin, resulting in hemolysis, vasoocclusion, and multiorgan damage. While the pathophysiological cascade offers numerous targets for treatment, currently only two disease-modifying drugs have been approved in Europe and transfusion remains a mainstay of both preventing and treating severe complications of SCD. Allogeneic stem cell transplantation and gene therapy offer a curative option but are restricted to few patients due to costs and limited availability of donors. Key Message: Further efforts are needed to grant patients access to approved treatments, to explore drug combinations and to establish new treatment options.

Revised mechanism of hydroxyurea-induced cell cycle arrest and an improved alternative.

Replication stress describes endogenous and exogenous challenges to DNA replication in the S-phase. Stress during this critical process causes helicase-polymerase decoupling at replication forks, triggering the S-phase checkpoint, which orchestrates global replication fork stalling and delayed entry into G2. The replication stressor most often used to induce the checkpoint response in yeast is hydroxyurea (HU), a clinically used chemotherapeutic. The primary mechanism of S-phase checkpoint activation by HU has thus far been considered to be a reduction of deoxynucleotide triphosphate synthesis by inhibition of ribonucleotide reductase (RNR), leading to helicase-polymerase decoupling and subsequent activation of the checkpoint, facilitated by the replisome-associated mediator Mrc1. In contrast, we observe that HU causes cell cycle arrest in budding yeast independent of both the Mrc1-mediated replication checkpoint response and the Psk1-Mrc1 oxidative signaling pathway. We demonstrate a direct relationship between HU incubation and reactive oxygen species (ROS) production in yeast and human cells and show that antioxidants restore growth of yeast in HU. We further observe that ROS strongly inhibits the in vitro polymerase activity of replicative polymerases (Pols), Pol α, Pol δ, and Pol ε, causing polymerase complex dissociation and subsequent loss of DNA substrate binding, likely through oxidation of their integral iron-sulfur (Fe-S) clusters. Finally, we present "RNR-deg," a genetically engineered alternative to HU in yeast with greatly increased specificity of RNR inhibition, allowing researchers to achieve fast, nontoxic, and more readily reversible checkpoint activation compared to HU, avoiding harmful ROS generation and associated downstream cellular effects that may confound interpretation of results.

A contemporary evaluation of the frequency & factors associated with overt stroke across the lifespan: A Ghanaian sickle cell disease registry analysis.

BACKGROUND: Stroke is a devastating complication of Sickle Cell Disease (SCD) with significant mortality and substantial morbidity. The burden of prevalent stroke in SCD is highest in sub-Saharan Africa and estimated at 4.2 % to 6.4 % in the era where evidence-based prevention strategies such as use of hydroxyurea therapy and transcranial doppler ultrasound were not routine care. PURPOSE: To assess the contemporary frequency and factors associated with prevalent stroke across the lifespan in an SCD registry at the tertiary medical center in Ghana. METHODS: This is a cross-sectional study conducted at the Komfo Anokye Teaching Hospital, a tertiary medical center in the middle belt of Ghana. The center has comprehensive Sickle Cell Clinics for children, adolescents, and adults with a patient registry established as part of the Sickle Pan-African Research Consortium (SPARCo)-Ghana study from 2017 to date. Data captured in the registry and analyzed for the present study include demographics, stroke status using the WHO criteria supplemented by the Questionnaire for Verifying Stroke Free Status (QVSFS), use of hydroxyurea, and complete blood count. Logistic regression modeling was utilized to assess factors associated with stroke. RESULTS: Among a registry cohort of 4115 individuals with confirmed SCD, 35 (0.85 %, 95 % CI: 0.59-1.18 %) had overt or clinically confirmed stroke. The frequency of stroke differed significantly across the lifespan being 0.38 % (95 % CI: 0.12-0.64 %) among children <10 years, 1.23 % (95 % CI: 0.73-1.94 %) among adolescents aged 10 to 17 years, and 1.44 % (95 % CI: 0.66-2.71 %) among adults 18 years or more, p = 0.007. In adjusted analysis, each 10-year increase in age was associated with odds ratio, OR (95 % CI) of 1.90 (1.42-2.54) and hydroxyurea use, OR of 6.09 (2.65-13.99). The association between hydroxyurea and stroke observed in this cross-sectional study is not causal. CONCLUSION: Approximately 1 in 120 SCD patients in this large Ghanaian cohort had clinically overt stroke. The gradual uptake of hydroxyurea therapy into routine care for SCD in this resource-limited setting, may partly explain the lower frequency of stroke.

Efficacy and safety of ruxolitinib vs best available therapy for polycythemia vera: An updated systematic review and meta-analysis.

Ruxolitinib, a JAK1/JAK2 inhibitor, has been shown to have lower thromboembolism rates compared to placebo in polycythemia vera (PV) patients. This meta-analysis evaluates ruxolitinib's efficacy and safety against best available therapy (BAT) in patients with PV and in hydroxyurea-resistant/intolerant PV patients. A comprehensive literature search was conducted up to November 2023. We compared ruxolitinib and BAT for efficacy and safety endpoints. Six studies involving 1061 patients were analyzed, with 620 on BAT and 441 on ruxolitinib. Ruxolitinib showed higher hematocrit control (p = 0.015) and treatment response (p = 0.04) compared to BAT. It also significantly improved Myeloproliferative Neoplasms-Symptom Assessment Form scores (MPN-SAF) (p < 0.01). Additionally, patients with PV treated with ruxolitinib had higher rates of nonmelanoma skin cancer (p < 0.01). In subgroup analyses focusing on patients resistant or intolerant to hydroxyurea, ruxolitinib maintained its efficacy, significantly improving treatment response (p < 0.01) and significant improvements in MPN-SAF (p = 0.02) score when compared to BAT. The safety profile was consistent with the overall analyses, showing significantly reduced thromboembolism rates (p = 0.04), increased rates of anemia (p = 0.01), and increased herpes zoster infections (p = 0.02). Ruxolitinib outperforms BAT in PV and patients with PV-resistant or intolerant to hydroxyurea, offering better hematocrit control and reducing symptomatic burden and thromboembolism risk. Yet, it is associated with higher rates of anemia, herpes infection, and skin cancer.

Adherence outcomes of a liquid hydroxyurea delivery program in a pediatric population.

BACKGROUND: Hydroxyurea remains underutilized in the pediatric sickle cell population despite its well-known efficacy in decreasing sickle cell complications and hospitalizations. Access to refills and liquid formulation remains a critical barrier to adherence to hydroxyurea regimens. This study was undertaken to determine the clinical impact of home-delivering compounded liquid hydroxyurea (LHU) to pediatric patients with sickle cell disease. PROCEDURE/METHODS: A retrospective cohort study was conducted using electronic health records and pharmacy databases. Pediatric patients younger than 21 years of age at the time of hydroxyurea initiation from March 2016 to July 2020 who received compounded LHU from Boston Medical Center Pharmacy were included. The primary outcomes of the study were drug adherence (assessed by evaluating the proportion of days covered [PDC]), rates of acute care utilization before and after enrolling in the LHU delivery program. RESULTS: The final cohort included 41 patients, showing a significant decrease in hospitalizations (p = .01) and acute chest syndrome episodes (p = .03) after the initiation of the LHU delivery program. In comparing hydroxyurea-naïve patients with those previously exposed to hydroxyurea, the latter group had lower hospitalization rates (p = .01), fewer vaso-occlusive event (VOE) episodes (p = .02), and fewer emergency department (ED) visits (p = .01). The median PDC value 1 year post initiation of LHU was 95. CONCLUSIONS: Home delivery of compounded LHU from the pharmacy to pediatric sickle cell disease patients improved access to hydroxyurea, and was linked to reduced hospitalizations and acute chest syndrome episodes. This advancement in cost savings and improved patient outcomes is a significant step forward in pediatric hematology. By overcoming access barriers, home delivery programs can greatly enhance outcomes among pediatric patients with sickle cell disease.

Nearly complete hair re-pigmentation in an older patient treated with hydroxyurea for essential thrombocytosis.

INTRODUCTION: Employed in the treatment of malignancies and non-neoplastic conditions, hydroxyurea is associated with integumentary adverse effects, including skin discoloration, xerosis, pruritus, cutaneous atrophy, chronic leg ulcers, oral ulcerations, alopecia, and some nail abnormalities. CASE REPORT: A 77-year-old woman was diagnosed with essential thrombocytosis and started on low dose hydroxyurea. After 20 weeks of treatment, she experienced an unexpected change in hair color from gray to dark brown, without using hair dye or supplements. She later developed bilateral dorsal hand melanoderma, melanonychia, and onychodystrophy. MANAGEMENT AND OUTCOME: It was decided to monitor the patient with no action taken as she was happy with this side effect of hydroxyurea. The platelet count has remained in excellent control. The dark brown hair color persisted over time. DISCUSSION/CONCLUSION: Hair hyperpigmentation likely occurred through melanocyte activation via hydroxyurea. Severe side effects may require dosage adjustments, while milder effects can be monitored closely. The newly observed hair color restoration in this case highlights potential dual (therapeutic and aesthetic) applications of this class of agents.

Prevalence of Pulmonary Hypertension among Sudanese Patients with Sickle Cell Disease.

Background: Sickle Cell Disease (SCD) is a hereditary condition characterized by aberrant red blood cell morphology, leading to persistent hemolytic anemia. The consequential impact of SCD on the pulmonary vasculature can result in pulmonary hypertension (PHT), a severe complication that detrimentally affects the well-being and survival of individuals with SCD. The prevalence and risk determinants of PHT in SCD patients exhibit variations across diverse geographical regions and populations. This study aims to ascertain the prevalence of PHT among Sudanese SCD patients and identify associated factors. Methods: A cohort of thirty-one adult sickle cell disease (SCD) patients, as confirmed by hemoglobin electrophoresis, were recruited for participation in this cross-sectional study. Comprehensive data encompassing demographic, clinical, and laboratory parameters were collected. Doppler echocardiography was employed to quantify pulmonary arterial systolic pressure (PASP) and evaluate right ventricular size and function. Results: Within our cohort, the prevalence of PHT was 29%. Active cigarette smoking demonstrated a significant association with PHT (P=0.042), while hydroxyurea therapy exhibited no noticeable impact on PHT (P=0.612). Conclusion: Our investigation revealed a PHT prevalence of less than one-third in our SCD patient population, aligning with prior studies. Notably, independent of other factors, cigarette smoking emerged as a distinct risk factor for PHT in SCD patients. This highlights the potential utility of smoking cessation as an intervention to delay the onset of this condition. However, further research is imperative to elucidate the mechanisms through which smoking contributes to PHT development in individuals with SCD.

Esophageal and Ileal Ulcers Caused by Hydroxycarbamide: A Case Report and Literature Review.

Hydroxycarbamide, an antimetabolic agent used to treat myeloproliferative disorders, causes side effects, including myelosuppression, skin ulcers, and oral mucositis. Gastrointestinal ulcers are uncommon, and esophageal ulcers have not been previously reported. We present the case of a 74-year-old woman who developed esophageal and ileal ulcers after hydroxycarbamide treatment. Our case and previous reports suggest that hydroxycarbamide can cause ulcers throughout the gastrointestinal tract, which can improve rapidly after discontinuing medication. When new signs and symptoms occur, drug-induced etiologies should be considered as a potential cause. Timely diagnostic treatment with discontinuation of medication is crucial in such cases.

Early Detection of Renal Complication in Children With Sickle Cell Disease: A Single Center Prospective Study.

INTRODUCTION: This observational cross-sectional study aimed to identify predictors of renal complications in pediatric patients with sickle cell disease (SCD) at King Salman Armed Forces Hospital, Tabuk, Saudi Arabia, over six months from February 2023 to July 2023. The study evaluated microalbuminuria as an early indicator of renal injury and explored its correlations with clinical and laboratory parameters and abdominal ultrasound (US) findings. METHODS: Included were pediatric patients aged 1 to 14 years with confirmed SCD, excluding those with acute infections or pre-existing renal diseases. Data from 100 patients' electronic medical records were analyzed using IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York, United States), with a significance set at p ≤ 0.05. RESULTS: The mean age was 7.6 ± 3.3 years, with 51 males and 49 females; 11 were diagnosed with Hb-S-beta thalassemia. Hydroxyurea (HU) compliance was high, with only four non-compliant patients, though all took folic acid. Among 42 tested for albuminuria, all had negative results (<30 mg/g creatinine). A significant association was found between SCD diagnosis and kidney, ureter, and bladder (KUB) US results (p=0.008), with abnormal KUB findings more prevalent in the Hb-S-beta thalassemia group. Patients with abnormal KUB results had significantly lower mean weight (p=0.024). Additionally, Hb-S-beta thalassemia patients had lower mean weight than hemoglobin SS (HGSS) patients (p=0.04). Though not statistically significant, Hb-S-beta thalassemia patients had higher mean systolic blood pressure (p=0.053). CONCLUSION: Significant associations were identified between SCD diagnosis type and renal US results, with lower body weight emerging as a potential predictor of renal complications. High HU compliance and its impact on renal outcomes warrant further investigation. Routine monitoring of microalbuminuria and KUB US may aid early detection of renal complications in pediatric SCD patients. Further studies with larger sample sizes are recommended to validate these findings and develop comprehensive renal protective strategies.

The Association Between Dental Caries and Salivary Buffering Capacity in Syrian Patients Diagnosed with Sickle Cell Disease.

Background Sickle cell disease (SCD) is a genetic disorder caused by mutations in the HBB gene, resulting in the abnormal shape of red blood cells. This condition is accompanied by various oral manifestations including salivary gland dysfunction leading to a heightened susceptibility to dental caries. This disorder is primarily treated with hydroxyurea. This study aims to assess dental caries utilizing the decay, missing, filling teeth (DMFT) index and evaluate salivary buffering capacity in patients diagnosed with SCD (HbSS type). The study also aims to assess the relationship between DMFT and salivary buffering capacity. Additionally, the study aimed to find a correlation between treatment with hydroxyurea and changes in both dental caries and salivary buffering capacity. Methods This case-control study enrolled a total of 100 participants aged between 20 and 50 years. The participants were divided into two groups: the study group, which comprised 70 individuals diagnosed with SCD (HbSS type), who were asked to report their current use of hydroxyurea, and the control group, which included 30 healthy individuals. Dental caries were assessed using the DMFT index, while salivary buffering capacity was measured using a pH meter model 420A device. Results The study group exhibited a mean DMFT index value of 6.39 compared to 5.20 in the control group. This difference was statistically significant (P-value=0.037), indicating higher DMFT values among patients with SCD. Salivary buffering capacity was significantly lower in the study group compared to the control group, with average values of 6.47 and 6.88, (P-value=.022). Interestingly, the administration of hydroxyurea impacted salivary buffering capacity, resulting in lower values for individuals using the drug (P-value=0.039). Conversely, hydroxyurea did not have a significant effect on DMFT values (P-value=0.317). Conclusion SCD increases susceptibility to dental caries and is associated with significant changes in salivary composition. At the same time, the potential negative impact of hydroxyurea is acknowledged.

Treatment comparison of hydroxyurea versus ruxolitinib in essential thrombocythaemia: A matched-cohort analysis.

Hydroxyurea is the preferred first-line cytoreductive treatment for high-risk essential thrombocythaemia (ET), but many patients are intolerant or refractory to hydroxyurea. Ruxolitinib has been shown to improve symptoms in patients with ET. This post hoc analysis compared the clinical outcomes of patients with ET who received hydroxyurea only with those who switched from hydroxyurea to ruxolitinib due to intolerance/resistance to hydroxyurea. Patients with ET refractory/intolerant to hydroxyurea treated with ruxolitinib in a completed phase 2 study (HU-RUX) were propensity score matched with patients who received hydroxyurea only in an observational study (HU). Changes in leukocyte and platelet counts were reported at 6-month intervals during the 48-month follow-up. Following propensity score matching, 37 patients were included for analysis in each cohort. Mean (standard deviation [SD]) leukocyte and platelet counts at index were higher for HU-RUX versus HU (leukocyte: 9.3 [5.1] vs. 6.8 [3.1] × 109/L; platelet: 1027.4 [497.8] vs. 513.9 [154.7] × 109/L), both of which decreased significantly from index to 6 months through to 48 months in HU-RUX (mean [SD] change from index at 6 months-leukocyte: -1.8 [4.6] × 109/L; platelet: -391.7 [472.9] × 109/L; at 48 months-leukocyte: -3.8 [5.3] × 109/L; platelet: -539.0 [521.8] × 109/L), but remained relatively stable in HU (mean [SD] change from index at 6 months-leukocyte: 0 [1.8] × 109/L; platelet: -5.7 [175.3] × 109/L; at 48 months-leukocyte: -0.1 [2.7] × 109/L; platelet: -6.9 [105.1] × 109/L). In conclusion, these results demonstrate that switching from hydroxyurea to ruxolitinib in patients with ET who are intolerant or refractory to hydroxyurea could improve abnormal haematologic values similar to those who receive first-line hydroxyurea.

Utilization and Perceptions of Hydroxyurea Therapy Among Adult Patients With Sickle Cell Disease in Al Ahsa, Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Sickle cell disease (SCD) is a prevalent genetic disorder characterized by abnormal hemoglobin formation, resulting in severe complications. Hydroxyurea (HU) therapy has demonstrated efficacy in reducing SCD-related complications; however, its utilization patterns and patient perceptions remain underexplored, particularly in the Al Ahsa region of Saudi Arabia. OBJECTIVE: This cross-sectional study aimed to assess the prevalence of HU usage among adult patients with SCD in Al Ahsa; identify the barriers to starting, maintaining, and discontinuing HU therapy; and evaluate the patient-reported outcomes associated with its use. METHODS: Data were collected through face-to-face surveys and medical record reviews of adult SCD patients attending outpatient clinics in the Hereditary Blood Diseases Center of Al Ahsa, Saudi Arabia, between December 2023 and March 2024. Descriptive statistics and inferential analyses were performed using SPSS version 26. RESULTS: A total of 345 adult SCD patients were included, with a mean age of 34.12 ± 11.1 years. Most participants were male (58.6%) and unmarried (55.4%). HU utilization was reported by 57.1% of the participants, with the highest adherence observed among older age groups (p = 0.001). Significant improvements in pain severity, hospitalization rates, and quality of life were reported among HU users (p < 0.001). Common barriers to HU use included concerns about side effects, lack of medical justification, and absence of medical advice. CONCLUSION: This study provides valuable insights into the utilization and perceptions of HU therapy among adults with SCD in Al Ahsa, Saudi Arabia. Addressing identified barriers and promoting patient education are crucial for optimizing therapy adherence and improving clinical outcomes in this population.

Thalidomide and Hydroxyurea in Transfusion-Dependent Thalassemia: Efficacy, Safety Profile and Impact on Quality of Life.

Transfusion-dependent thalassemia (TDT) is a major public health concern in India, requiring regular transfusions for survival. There is also significant morbidity caused by iron overload and transfusion related infections. Novel therapies targeting fetal hemoglobin induction are the need of the hour in resource-poor institutions for patients where transplant is not feasible for various reasons. This single arm, non-randomised prospective trial evaluated the efficacy and safety of a combination of low dose thalidomide and hydroxyurea in TDT along with the impact on quality of life (QoL). It included 41 TDT patients, who failed a reasonable trial of hydroxyurea. Complete response (CR) was defined as transfusion independence and partial response (PR) denoted at least a 50% reduction in transfusion requirement. The rest were defined as non-responders (NR). The mean age of the cohort was 20.78 years (range 12-45 years). There were 13 males and 28 females. Nineteen (46.3%), 7 (17.1%), and 15 (36.6%) patients achieved CR, PR, and no response respectively. The overall response rate (CR + PR) was 63.4%. There was a significant increase in hemoglobin levels with decrement in transfusion burden and ferritin levels. There were no significant adverse reactions. No significant predictors of response were found including amongst genetic modifiers. It improved the health related QoL amongst responders. The combination of thalidomide and hydroxyurea appear safe and effective in the reduction in transfusion requirement of TDT patients. The judicious use of these drugs can improve the quality of life and pave the way for patients not eligible for a stem cell transplant.

Hydroxyurea in the sickle cell disease modern era.

INTRODUCTION: Sickle cell disease is an inherited disorder characterized by hemoglobin S polymerization leading to vaso-occlusion and hemolytic anemia. These result in a variety of pathological events, causing both acute and chronic complications. Millions around the world are affected by sickle cell disease with predominance in sub-Saharan Africa. Hydroxyurea was the first drug approved for use in sickle cell disease to reduce the occurrence of painful crises and blood transfusions in patients with frequent, moderate to severe painful crises. AREAS COVERED: With the development of new therapeutics, the role of hydroxyurea is evolving. This narrative review aims to provide clinical data, safety information, and supplementary evidence for the role of hydroxyurea in the current era of sickle cell disease. A comprehensive literature search of databases, including PubMed and Cochrane Library, was conducted from 1963 to 2024. EXPERT OPINION: Even though new medications have been approved for sickle cell disease, hydroxyurea remains the gold standard. Hydroxyurea is not only a disease modifier but it has additional clinical benefits, it is affordable, and its longevity has prompted expanded research in areas such as underutilization and pharmacogenomics. As the treatment landscape evolves, hydroxyurea's long-standing record of efficacy and safety continues to support its role as a key agent in disease management.

Primary polycythaemia: A neglected risk factor.

In this case series, we report a 32-year-old male patient with myocardial infarction and 45-year-old female with portal vein thrombosis with splenic infarcts, which were the initial manifestations of polycythaemia vera. The awareness of myeloproliferative disorders as a possible underlying disease-especially in young patients presenting with myocardial infarction and portal venous thrombosis-is crucial for clinical management, as a missed diagnosis can worsen the patients' further prognosis.

Stability of extemporaneously prepared hydroxyurea solutions.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To evaluate the stability of a new, more convenient (<30 minutes for preparation), extemporaneously prepared hydroxyurea solution over 78 days. METHODS: A high-performance liquid chromatography (HPLC) method using a hydrophilic interaction chromatography (HILIC) column was developed and validated to accurately measure the concentration of hydroxyurea directly from solution without the need for chemical derivatization. Hydroxyurea was dissolved in sterile water in less than 5 minutes to yield a 100-mg/mL solution, which was then diluted by an equal volume of ORA-sweet vehicle to yield a 50-mg/mL extemporaneously prepared solution of hydroxyurea. The solution samples were kept at refrigeration (4 °C), room temperature (26 °C), and elevated temperature (40 °C) for 78 days. RESULTS: The 50-mg/mL solutions of hydroxyurea in a 1:1 mixture of water and ORA-sweet kept at 4 °C and 26 °C showed no significant loss of potency (<2%) after 78 days. The solutions kept at 40 °C showed greater than 10% loss of potency after 28 days. CONCLUSION: Extemporaneously compounded hydroxyurea 50-mg/mL solutions prepared in a 1:1 mixture of water and ORA-Sweet and stored in amber polypropylene plastic bottles were stable for at least 78 days at room temperature and under refrigeration.

Morbidity pattern and impact of hydroxyurea therapy among sickle cell patients in Raipur district of Chhattisgarh.

Background: Sickle cell disease (SCD) is a disorder marked by a single-point mutation in the beta-globin gene. Hydroxyurea is a globally accepted disease-modifying agent that sounds to be effective in managing clinically and probably preventing complications of SCD. The current study aims to document the morbidity pattern and impact of Hydroxyurea therapy in the Outpatient Department of Sickle Cell Institute, Raipur. Materials and Methods: This cross-sectional study was conducted among randomly selected sixty-five patients (adults and children above six years). After obtaining informed consent, relevant data were collected in a predesigned pretested questionnaire. The appropriate statistical exercise was applied for the interpretation of results and inferences. Results: Acute febrile illness 54 (83%) and 53 (81.5%) reported pain crisis observed to have the most common morbidity among the study subjects, followed by 55.4% (36), 33 (50.8%) jaundice and difficulty breathing, respectively. Joint pain was the most commonly observed complaint, particularly at the knee joint (76.9%). Other complaints such as hand-foot syndrome (24.6%), epistaxis (27.7%), and acute chest syndrome (21.5%). Vaso-occlusive crisis (72.4%), difficulty in walking (60.0%) and eyesight (35.4%), leg ulcers (9.2%), and dactylitis (3.1%) were also documented as clinical manifestations among study participants. Less than half (44.46%) had an awareness about SCD. Hydroxyurea therapy was highly significant in improving the patient's clinical picture (P < 0.01), especially following the frequency of hospitalization and the requirement for blood transfusion. Conclusion: Pain crisis is the most common morbidity among study participants with a low level of knowledge about SCD with febrile illness. Hydroxyurea therapy was found to be quite effective as a disease-modifying therapy, especially for reducing the frequency of blood transfusion and lowering hospitalization rates among SCD patients.

Assessing multilevel barriers to hydroxyurea adherence in youth with sickle cell disease using pharmacy-based refill records.

BACKGROUND: Suboptimal medication adherence is common across youth with chronic health conditions and may contribute to health disparities and adverse health outcomes, especially in underserved communities. METHODS: Using pharmacy prescription records and guided by the World Health Organization Multidimensional Adherence Model, we examined patient-, treatment-, and health system-related factors that may affect hydroxyurea adherence in 72 youth with sickle cell disease (SCD), 10-18 years who had participated in the multisite "Hydroxyurea Adherence for Personal Best in SCD" (HABIT) feasibility (6 months) and efficacy (12 months) trials. Pharmacy data were collected from the year prior to study entry through the duration of each trial. We also examined hydroxyurea dose at baseline, prescribing patterns (hydroxyurea formulation and dose prescribed), quantity of hydroxyurea dispensed, and number of daily capsules/tablets prescribed. Data were analyzed using descriptive statistics. RESULTS: On average, youth were prescribed 1095 ± 402 mg hydroxyurea per day, requiring ingestion of 3 or more capsules for 39.4% of youth. Frequently identified potential barriers were complex medication regimens in which dose of hydroxyurea differed by day of week (47.2%); receipt of an inadequate (< 30 days) supply of hydroxyurea from the pharmacy ≥ 3 times during record collection period (29.2%); and prescription of hydroxyurea suspension suggesting problems swallowing capsules (22.2%). In this sample, most youth were exclusively prescribed 500 mg capsules (62.5%), which was associated with complex medication regimens (RR 3.0, 95% CI 1.4-6.7). Potential barriers were common, occurred at all levels and are potentially modifiable with targeted interventions at the treatment- and health system-related levels.

Dermatomyositis-like skin eruptions under hydroxyurea therapy conceal TP53-mutated atypical keratinocytes: A histopathologic and molecular pathologic case series.

Hydroxyurea is an antimetabolite that inhibits DNA synthesis and is used as a treatment option in chronic myeloproliferative disorders. Rarely, "dermatomyositis (DM)-like" skin lesions are observed after long-term therapy. In this case series, five skin biopsies of four patients were evaluated by histology, immunohistochemistry, and next-generation sequencing of the TP53 gene locus. All biopsies showed focal basal pleomorphic keratinocytes and suprabasal aberrant p53 expression as well as sparse to severe vacuolar interface dermatitis. Histopathologically, "DM-like" skin lesions can be clearly distinguished from DM by marked subepidermal fibrosis, vascular proliferation, and the absence of dermal mucin deposits. In 75% of the specimens multiple, partly inactivating and/or pathogenic point mutations of TP53 were found in low frequencies. "DM-like" skin eruptions as a long-term consequence of hydroxyurea therapy are possibly not chemotherapy-associated benign toxic changes, but rather inflammatory reactions to complex keratinocyte alterations that clinically mimic the picture of DM. Synergistic mutagenic effects of hydroxyurea and sunlight might be responsible for this unique drug side effect and could provide a pathogenic link to the known increased risk of skin cancer in these patients.