Report of renal allograft tuberculosis a decade after transplant: challenges in diagnosis and management.

Post-transplant infections constitute an important cause of morbidity and mortality in renal transplant recipients worldwide. Tuberculosis (TB) contributes significantly to this burden in endemic countries, such as India. We report a case of renal allograft TB, 10 years post-transplantation, diagnosed during a routine outpatient visit. An asymptomatic rise in serum creatinine level and a 6 month history of immunosuppressive drug non-compliance prompted evaluation of graft dysfunction. Biopsy of the renal allograft tissue suggested chronic active antibody mediated rejection with epithelioid granulomas in the interstitium. Guided by kidney biopsy, further testing with urine acid fast bacilli and urinary GeneXpert yielded positive results for TB. Treatment of TB was further complicated by the development of anti-tubercular therapy induced hepatitis and immune reconstitution inflammatory syndrome, which were managed with the reintroduction regimen and escalation of steroid dose, respectively. Our case highlights the atypical presentation and challenges in managing patients with TB in a post-renal transplant setting.

Geospatial mapping of public sentiment and infodemic on human papillomavirus vaccination in India: An indication to formulation of strategies for effective implementation.

The implementation of Human Papillomavirus (HPV) vaccination is crucial for eliminating cervical cancer in India. The infodemic, characterised by misleading information, could hinder the successful implementation of the initiative. Misinformation related to the HPV vaccine, such as rumours, has been reported and circulated, contributing to an alarming pattern of vaccine hesitancy observed on social media. This study aimed to identify the public sentiment towards HPV vaccination based on the 'Behavioral and Social Drivers (BeSD)' framework through geospatial, content and sentiment analysis. A total of 1,487 tweets were extracted. After preprocessing, 1010 tweets were identified for sentiment and content analysis. The sentiments expressed towards the HPV vaccine are mixed, with a generally positive outlook on the vaccines. Within the population, there is a pervasive proliferation of misinformation, primarily focusing on vaccine safety and efficacy, contentious subjects, ethical considerations, and a prevalent sense of uncertainty in selecting the appropriate vaccine. These observations are crucial for developing targeted strategies to address public concerns and enhance vaccination rates. The insights gained from these results will guide policymakers, healthcare practitioners, and public health organisations to implement evidence-based interventions, thereby countering vaccine hesitancy and improving public health outcomes.

Assessment of the Utility of Point-of-Care Testing Incorporating Ultrasound and Arterial Blood Gas in Patients with Acute Febrile Illness in the Emergency Department to Determine Disease Severity, Disposition, Need for Ventilation and Renal Replacement Therapy.

Introduction: Acute febrile illness (AFI) patients present to the emergency department (ED), with fever to multi-organ dysfunction. There is a lack of early point-of-care-based disposition criteria in AFI patients regarding the need for intensive care unit (ICU) or high dependency unit (HDU) care. Methods: We enrolled 100 patients with AFI presenting to the ED and evaluated using point-of-care ultrasound with two-dimensional echocardiography (ECHO), lung ultrasound score (LUS), renal arterial resistive index (RRI), and arterial blood gas. The need for ICU/HDU admission, ventilation (either noninvasive or invasive), and renal-replacement therapy (RRT) within 48 h of hospitalization was noted. Results: Ninety-five patients were included in the analysis. 72 (75.8%) patients required either ICU or HDU admission, 45 (47.4%) required ventilatory support (either noninvasive or invasive), and 32 (33.7%) required RRT. After logistic regression, LUS ≥16, and arterial lactate ≥12 mg/dL were independent predictors of the need for ICU or HDU admission. The respiratory rate (RR) ≥28/minute, LUS ≥16 and RRI ≥61 were the independent predictors of the need for ventilation. The MAP ≤73 mmHg, LUS (≥16), and RRI (≥67) were the predictors of the need for RRT. Conclusion: In AFI patients presenting to the ED, the MAP, LUS, and lactate are predictors of the need for ICU/HDU admission. The LUS and RRI were predictors of the need for RRT whereas the RR, LUS, and RRI were the predictors of the need for ventilation.

Phytotherapy in Diabetic Foot Ulcers: A Promising Strategy for Effective Wound Healing.

Despite the advancement in wound care, the effective therapy of chronic diabetic ulcers continues to be a challenge. Wound healing is a highly controlled process, which involves a sequence of complex overlapping steps. This healing pathway comprises of hemostasis, inflammation, proliferative, and remodeling phases. Recent evidence suggests that phytomedicines can prevent or repair different kinds of destructive cellular damage, including chronic wounds. Several phytochemicals such as polyphenols, alkaloids, flavonoids, terpenoids, and glycosides have pleiotropic effects, including stimulation of fibroblast proliferation, the main step in wound healing. Besides, the mechanism involves induction of collagen synthesis, migration, and reepithelization and their antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory actions. Similarly, the use of phytochemicals alone or as an adjuvant with standard therapy has demonstrated promising results in managing complications in the diabetic foot. For instance, the extract of Carica papaya has been shown antioxidant, antimicrobial, and anti-inflammatory, and immunomodulatory effects, which, together with proteolytic enzymatic activity, contributes to its wound healing property. It is generally believed that phytotherapy has no or minimal toxicity than synthetic therapeutic agents, favoring its use in diabetic foot ulcer management. The current review highlights the selected phytochemicals and their sources; and potential application in diabetic foot ulcer management.Key teaching points and nutritional relevanceCurrently, phytochemicals have been shown wide potential in disease. management including alleviating clinical manifestations, preventing degenerative disease, and curing illness.Increased evidence of phytochemical as anti-infective and anti-inflammatory suggests its role in the management of diabetic foot ulcer(DFU).Potential benefit along with minimal adverse effect favors its application as adjuvant therapy.Further research is needed to standardize its dose and formulation to enhance its clinical application in DFU management.

Cefepime-induced Neurotoxicity: A Retrospective Cohort Study in a South-Indian Tertiary Healthcare Facility.

BACKGROUND: Cefepime is a fourth-generation cephalosporin with a broad spectrum coverage and anti-pseudomonal activity. The safety profile of cefepime was relatively favourable until neurotoxicity was first reported in 1999. Despite cefepime-induced neurotoxicity (CIN), it continues to be a principal part of parenteral treatment for various infections. OBJECTIVE: The study aimed to determine the incidence and risk factors for CIN compared to other antibiotics. METHODS: A retrospective cohort study was conducted involving 738 patients over eight months in Kasturba Medical College and Hospital, Manipal, India. Patients with cefepime were selected as study cohort (SC; n= 496), and other antibiotics were included in the reference cohort (RC; n=242). RESULTS: The results showed that 53 (10.7%) patients developed neurotoxicity in the SC, whereas 12 (5%) patients in the RC. A significant association was found between neurotoxicity and cefepime use (X2 =6.641; p=0.01). SC has a 2.29 times increased risk of neurotoxicity than RC (OR: 2.29; 95% CI: 1.2-4.38). Risk estimation showed that renal failure patients had a 5.5 times higher risk for CIN than non-renal failure patients (OR: 5.5; 95% CI: 2.98 - 10.17). CIN symptoms were disorientation (38.5%), loss of consciousness (23.1%), drowsiness (18.5%), etc. The calculated number needed to harm (NNH) for cefepime was 17.2. CONCLUSION: The study found a higher incidence of CIN compared to other antibiotics-induced neurotoxicity and a harmful association between cefepime use and CIN development. Besides, renal failure is a risk factor for CIN. Therefore, the study warrants the use of cefepime, where no other alternatives are available.

Clinical profile, diagnosis, treatment, and outcome of patients with tubercular versus nontubercular causes of spine involvement: A retrospective cohort study from India.

Background: In tuberculosis (TB) endemic areas, other pyogenic causes of spine involvement may be missed. The study aimed to describe TB and non-TB causes of spine involvement and identify features that can help in differentiating them. Methods: A retrospective cohort study was conducted to screen the clinical records of all admitted patients (Kasturba Hospital, Manipal) in 2018-20 for a diagnosis of spondylitis and/or sacroiliitis. The clinical features, radiological findings, laboratory parameters, treatment details, and outcomes were compared among those diagnosed with confirmed TB, confirmed brucellosis, or confirmed pyogenic infection. A scoring system was also developed to differentiate spondylodiscitis due to tuberculous and pyogenic causes. The qualitative variables were compared using the Chi-square test, while quantitative variables were compared using the one-way analysis of variance test. Results: Of 120 patients with spine infections, a total of 85 patients were confirmed with the microbiological diagnosis of interest. Involvement of the thoracic spine, longer duration of illness, and caseous granulomatous reaction on histopathology was more common in TB patients. Male gender, involvement of lumbar vertebra, and neutrophilic infiltrate on histopathology were more common in brucellosis patients. Male gender, diabetes mellitus, involvement of lumbar vertebra, neutrophilic infiltrate on histopathology, leukocytosis, and increased C-reactive protein were more commonly seen in patients with pyogenic infection. The scoring system had a sensitivity and specificity of 75% and 91%, respectively, when used to differentiate TB from pyogenic infection. Conclusions: In resource-limited settings, suggestive findings can be used to decide empiric therapy.

Hydatid Cyst in Liver Masquerading As Metastatic Deposits From Ovarian Carcinoma.

Metastatic deposits from primary ovarian malignancy can manifest as cystic masses in the liver. In endemic areas, hydatid disease is an important differential in all cases of cystic hepatic masses. We report a case of a 55-year-old lady who presented with progressive abdominal distension and was diagnosed with primary ovarian high-grade serous carcinoma. Imaging revealed concurrent lesions in the liver that were thought to be metastatic deposits but was later diagnosed as hydatid cyst based on radiologic features and serology. We report this rare case to highlight the importance of suspecting a hydatid cyst in endemic areas and its varied manifestations.

Cryptococcal spondylodiscitis in a non-HIV patient with CD4 lymphocytopenia.

Infections that affect the intervertebral discs and vertebrae are known as spondylodiscitis. Such infections are commonly caused by pyogenic organisms, particularly Staphylococcus aureus, and hematogenous spread is the most common route. Non-pyogenic infections include Mycobacterium tuberculosis and Brucellosis. Mycotic infections are becoming more common, in line with the growing number of immunodeficiency disorders. Cryptococcus is included among these mycotic infections. We present a case of such an infection in a non-immunocompromised patient with a known history of treatment with antitubercular therapy. A 52-year-old man came to our hospital with a backache of one-month duration and progressive neurological deficits of the lower limbs of one-week duration. His imaging studies were suggestive of spondylodiscitis at the D10-11 and D11-12 levels with a left paraspinal abscess. The patient underwent anterolateral decompression, biopsy, and instrumented posterior spinal fusion. The pus grew Cryptococcus, and histopathology confirmed Cryptococcal spondylodiscitis. The patient was treated with parenteral amphotericin B and fluconazole. A mycotic infection must be considered in the differential diagnosis of infectious spondylodiscitis.

Paraparesis in a patient with advanced HIV infection: a diagnostic conundrum.

In patients with HIV infection, lower limb weakness is a result of the pathological involvement of the brain, spinal cord or peripheral nervous system. The pathological process can be opportunistic infections, nutrient deficiencies, neoplastic infiltration or HIV itself. Here, we present the case of a 50-year-old manual labourer who presented with gradually progressive lower limb weakness, sensory disturbances, impotence and urinary urgency. He was diagnosed with HIV during evaluation. Based on the presentation and other supportive laboratory and radiological evidence, the following differentials were considered: vacuolar myelopathy, amyotrophic lateral sclerosis and myeloradiculopathy. The patient was initiated on antiretroviral therapy, and he showed significant improvement of symptoms on follow-up. We report this case to discuss the diagnostic puzzle.

Remdesivir therapy in patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To perform a systematic review and meta-analysis of randomized controlled trials that examined remdesivir treatment for COVID-19. MATERIALS AND METHODS: A systematic literature search was performed using Pubmed, Embase, and ClinicalTrials.gov to identify studies published up to October 25, 2020 that examined COVID-19 treatment with remdesivir. A total of 3 randomized controlled trials that consisted of 1691 patients were included in the meta-analysis. RESULTS: The odds for mechanical ventilation (MV) or extracorporeal membrane oxygenation (ECMO) following treatment was significantly lower in the remdesivir group compared to the control group (OR = 0.48 [95% CI: 0.34; 0.69], p < 0.001). The odds of early (at day 14/15; OR = 1.42 [95% CI: 1.16; 1.74], p < 0.001) and late (at day 28/29; OR = 1.44 [95% CI: 1.16; 1.79], p = 0.001) hospital discharge were significantly higher in the remdesivir group compared to the control group. There was no difference in the odds for mortality in patients treated with remdesivir (OR = 0.77 [95% CI: 0.56; 1.06], p = 0.108). CONCLUSIONS: Remdesivir attenuates disease progression, leading to lower odds of MV/ECMO and greater odds of hospital discharge for COVID-19 patients. However, remdesivir does not affect odds of mortality.

In silico Study to Evaluate the Antiviral Activity of Novel Structures against 3C-like Protease of Novel Coronavirus (COVID-19) and SARS-CoV.

BACKGROUND: Globally, over 4.3 million laboratory confirmed cases of COVID-19 have been reported from over 105 countries. No FDA approved antiviral is available for the treatment of this infection. Zhavoronkov et al., with their generative chemistry pipeline, have generated structures that can be potential novel drug-like inhibitors for COVID-19, provided they are validated. 3C-like protease (3CLP) is a homodimeric cysteine protease that is present in coronaviruses. Interestingly, 3CLP is 96.1% structurally similar between SARS-CoV and SARS-CoV-2. OBJECTIVE: To evaluate interaction of generated structures with 3CLP of SARS-CoV (RCSB PDB ID: 4MDS). METHODS: Crystal structure of human SARS-CoV with a non-covalent inhibitor with resolution: 1.598 Å was obtained and molecular docking was performed to evaluate the interaction with generated structures. The MM-GBSA and IFD-SP were performed to narrow down to the structures with better binding energy and IFD score. The ADME analysis was performed on top 5 hits and further MD simulation was employed for top 2 hits. RESULTS: In XP docking, IFD-SP and molecular dynamic simulation studies, the top 2 hits 32 and 61 showed interaction with key amino acid residue GLU166. Structure 61, also showed interaction with HIS164. These interactions of generated structure 32 and 61, with GLU166 and HIS164, indicate the binding of the selected drug within the close proximity of 3CLP. In the MD simulation, the protein- ligand complex of 4MDS and structure 61 was found to be more stable for 10ns. CONCLUSION: These identified structures can be further assessed for their antiviral activity to combat SARS-CoV and COVID-19.

Deep learning, computer-aided radiography reading for tuberculosis: a diagnostic accuracy study from a tertiary hospital in India.

In general, chest radiographs (CXR) have high sensitivity and moderate specificity for active pulmonary tuberculosis (PTB) screening when interpreted by human readers. However, they are challenging to scale due to hardware costs and the dearth of professionals available to interpret CXR in low-resource, high PTB burden settings. Recently, several computer-aided detection (CAD) programs have been developed to facilitate automated CXR interpretation. We conducted a retrospective case-control study to assess the diagnostic accuracy of a CAD software (qXR, Qure.ai, Mumbai, India) using microbiologically-confirmed PTB as the reference standard. To assess overall accuracy of qXR, receiver operating characteristic (ROC) analysis was used to determine the area under the curve (AUC), along with 95% confidence intervals (CI). Kappa coefficients, and associated 95% CI, were used to investigate inter-rater reliability of the radiologists for detection of specific chest abnormalities. In total, 317 cases and 612 controls were included in the analysis. The AUC for qXR for the detection of microbiologically-confirmed PTB was 0.81 (95% CI: 0.78, 0.84). Using the threshold that maximized sensitivity and specificity of qXR simultaneously, the software achieved a sensitivity and specificity of 71% (95% CI: 66%, 76%) and 80% (95% CI: 77%, 83%), respectively. The sensitivity and specificity of radiologists for the detection of microbiologically-confirmed PTB was 56% (95% CI: 50%, 62%) and 80% (95% CI: 77%, 83%), respectively. For detection of key PTB-related abnormalities 'pleural effusion' and 'cavity', qXR achieved an AUC of 0.94 (95% CI: 0.92, 0.96) and 0.84 (95% CI: 0.82, 0.87), respectively. For the other abnormalities, the AUC ranged from 0.75 (95% CI: 0.70, 0.80) to 0.94 (95% CI: 0.91, 0.96). The controls had a high prevalence of other lung diseases which can cause radiological manifestations similar to PTB (e.g., 26% had pneumonia, 15% had lung malignancy, etc.). In a tertiary hospital in India, qXR demonstrated moderate sensitivity and specificity for the detection of PTB. There is likely a larger role for CAD software as a triage test for PTB at the primary care level in settings where access to radiologists in limited. Larger prospective studies that can better assess heterogeneity in important subgroups are needed.

Point-of-Care Ultrasound for Extrapulmonary Tuberculosis in India: A Prospective Cohort Study in HIV-Positive and HIV-Negative Presumptive Tuberculosis Patients.

Diagnosing extrapulmonary tuberculosis (EPTB) is challenging. Point-of-care ultrasound (POCUS) for human immunodeficiency virus (HIV)-associated EPTB is applied in sub-Saharan Africa. This study aimed at evaluating the applicability of POCUS for diagnosing EPTB in HIV-positive and HIV-negative presumptive tuberculosis (TB) patients in India, a country of moderate relative TB and HIV burden. Presumptive TB patients at Kasturba Hospital, Manipal, India, prospectively underwent POCUS evaluating for pericardial, pleural and ascitic effusion, abdominal lymphadenopathy, and hepatic and splenic microabscesses. Findings were correlated with TB category (confirmed TB, clinical TB, unlikely TB), HIV status, and discharge diagnoses. A total of 425 patients underwent POCUS; 81 (20%) were HIV-positive. POCUS findings were more common in HIV/TB coinfected patients than in HIV-positive patients with unlikely TB (24/40 (60%) versus 9/41 (22%), P < 0.001). Abdominal lymphadenopathy and splenic microabscesses were strongly associated with TB in HIV-positive patients (P = 0.002 and P = 0.001). POCUS findings did not correlate with TB in HIV-negative patients; a third of HIV-negative patients with unlikely TB and POCUS findings had cancer, another third other infectious diseases. Sonographic findings were common in HIV-positive and HIV-negative presumptive TB patients. POCUS was a useful bedside test for the detection of HIV-associated EPTB. In HIV-negative patients, POCUS detected features associated with EPTB but also of malignancy and other infectious diseases.

Therapeutic Assessment of Primaquine for Radical Cure of Plasmodium vivax Malaria at Primary and Tertiary Care Centres in Southwestern India.

Acquaintance is scanty on primaquine (PQ) efficacy and Plasmodium vivax recurrence in Udupi district, Karnataka, India. We assessed the efficacy of 14 days PQ regimen (0.25 mg/kg/day) to prevent P. vivax recurrence. Microscopically, aparasitemic adults (≥18 years) after acute vivax malaria on day 28 were re-enrolled into 15 months' long follow-up study. A peripheral blood smear examination was performed with participants at every 1-2 month interval. A nested PCR test was performed to confirm the mono-infection with P. vivax. Of 114 participants, 28 (24.6%) recurred subsequently. The median (IQR) duration of the first recurrence was 3.1 (2.2-5.8) months which ranged from 1.2 to 15.1 months, including initial 28 days. Participants with history of vivax malaria had significantly higher risk of recurrence, with hazard ratio (HR) (95% CI) of 2.62 (1.24-5.54) (P=0.012). Severity of disease (11.4%, 13/114) was not associated (P=1.00) with recurrence. Of 28 recurrence cases, the nPCR proved that P. vivax mono-infection recurrence rate was at least 72.7% (16/22) at first recurrence. In Udupi district, PQ dose of 0.25 mg/kg/day over 14 days seems inadequate to prevent recurrence in substantial proportion of vivax malaria. Patients with a history of vivax malaria are at high risk of recurrences.

Spontaneous tumour lysis syndrome in a case of multiple myeloma - A rare occurrence.

We describe a case of a 40-year-old male patient who was found to have multiple myeloma with spontaneous tumour lysis syndrome (TLS), following a compression fracture of the L-2 vertebrae. Multiple myeloma was confirmed by bone marrow analysis and the M-band on serum protein electrophoresis. Hyperuricaemia (26.2 mg/dL), hyperkalaemia (> 7.0 mEq/L), hyperphosphatemia (16.2 mg of phosphorus/dL), normocalcemia and acute kidney injury, prior to anticancer treatment suggested spontaneous TLS. Inciting events for tumour lysis, such as chemotherapy, dehydration and exposure to steroids were absent. Patient received hydration, hypourecemic drugs and haemodialysis. This case report highlights the rare presentation of multiple myeloma with spontaneous TLS.

Candidal renal papillary necrosis conquered.

Renal papillary necrosis due to Candida albicans is a rare but treatable cause of acute renal failure. We report this case of a middle aged male with history of type 2 diabetes mellitus who presented with infected right lower extremity and right lower lobe pneumonitis with hypotension. Though, he improved initially, during his stay in the hospital, he developed acute renal failure. Blood culture grew Candida albicans and the renal biopsy revealed candidal renal papillary necrosis. He also had candidal retinitis on ophthalmoscopy examination. He was treated with parenteral fluconazole for two weeks followed by oral fluconazole for a total of 4 weeks. Following treatment, the patient improved symptomatically and his renal parameters returned to normal. This case illustrates the need to consider candidal papillary necrosis as a differential in an immunocompromised patient with acute renal failure. It is potentially reversible, nonetheless a diagnostic and therapeutic challenge.

Melioidosis presenting with mediastinal lymphadenopathy masquerading as malignancy: a case report.

INTRODUCTION: Melioidosis, endemic in Thailand and in the Northern Territory of Australia is an emerging infectious disease in India which can present with varied forms. A case of melioidosis, presenting as a rare anterior mediastinal mass which can masquerade as malignancy or tuberculosis, is described here. With treatment, our patient initially showed an increase in the size of mediastinal node and development of new submandibular node.. To the best of our knowledge, this phenomenon has not been documented in the literature and the same is highlighted in this case report. CASE PRESENTATION: A 43-year-old Asian man with diabetes presented with fever, loss of appetite, weight loss for one month and painful swelling below his left mandible for five days. An examination revealed an enlarged left submandibular lymph node and bilateral axillary lymph nodes. A chest X-ray showed mediastinal widening. Computed tomography of his thorax showed a lobulated heterogeneously enhancing anterior mediastinal mass encasing the superior vena cava suggestive of malignancy. An excision biopsy of the lymph node showed granulomas suggestive of tuberculosis but bone marrow culture and lymph node aspirate culture grew Burkholderia pseudomallei. He was treated with parenteral ceftazidime and amoxicillin-clavulanic acid. During the course of treatment, he developed an enlargement of the submandibular lymph node on the opposite side. It gradually subsided with the continuation of therapy orally with a combination of cotrimoxazole and doxycycline for six months. A repeat computed tomography chest scan showed resolution of the mediastinal mass. CONCLUSION: Melioidosis can present as a mediastinal mass that mimics tuberculosis or malignancy. During the initial phase of treatment of melioidosis, the appearance of new lymph nodes or an increase in the size of the existing lymph nodes does not mean treatment failure. Inexperienced clinicians may consider this as treatment failure and may switch treatment. To the best of our knowledge, this is the first report documenting this phenomenon in melioidosis cases.

Acute interstitial nephritis related to lansoprazole administration.

Acute interstitial nephritis (AIN) is a rare but serious adverse effect reported with proton pump inhibitors (PPIs). Only one report (2 cases) of AIN with lansoprazole is published in literature. A case of lansoprazole induced interstitial nephritis (biopsy supported) was reported in an elderly female patient admitted to the hospital with non specific symptoms after 45 days of treatment with the drug. A recovery was noticed upon withdrawal of the drug and treatment with corticosteroids. We consider this report as a valuable addition to the existing literature on this rare adverse effect with lansoprazole. This potentially serious adverse effect with PPIs including lansoprazole has to be given due consideration, especially taking into account the wide spread use of this group of agents.

Hydroxyurea induced perimalleolar ulcers.

Hydroxyurea (HU) is an antineoplastic drug commonly used to treat chronic myeloproliferative disorders. Common dermatological side effects include hyperpigmentation, scaling, erythema, alopecia, desquamation of face and hands. Leg ulceration following HU therapy is less common and very few cases have been reported so far. Objective of this paper is to increase the awareness of hydroxyurea induced leg ulcers which will aid in the early diagnosis and appropriate treatment. The first case was a chronic myeloid leukemia (CML) patient on HU 1.5 g/day for 5 yr, who had bilateral painful perimalleolar ulcers for 6 months. The second case was a CML patient on HU 1.5 g/day for 3 yr who developed bilateral lateral malleolar ulcers. Third case was a polycythemia vera (PV) patient on HU 1 g/day for 5 yr who presented with painful medial malleolar ulcer of 2 months. The last case of our report was an elderly PV patient on HU 1.5 g/day for 2 yr and presented with lateral malleolar ulcer which persisted on reducing the dose of HU. In all the 4 cases the ulcers healed on stopping HU. Our report confirms the association of chronic hydroxyurea therapy and perimalleolar ulcers which respond promptly after discontinuation of the drug. The heightened awareness among the physicians will promote early diagnosis and prompt relief from the agonizing ulcers.