Case presentation: a severe case of cobalamin c deficiency presenting with nephrotic syndrome, malignant hypertension and hemolytic anemia.

BACKGROUND: The etiology of nephrotic syndrome can vary, with underlying metabolic diseases being a potential factor. Cobalamin C (cblC) defect is an autosomal recessive inborn error of metabolism caused by mutations in the MMACHC gene, resulting in impaired vitamin B12 processing. While cblC defect typically manifests with hematological and neurological symptoms, renal involvement is increasingly recognized but remains rare. CASE PRESENTATION: We describe a 7-month-old male patient presenting with fatigue and edema. His first laboratory findings showed anemia, thrombocytopenia, hypoalbuminemia and proteinuria and further examinations reveals hemolysis in peripheric blood smear. During his follow up respiratory distress due to pleural effusion in the right hemithorax was noticed. And fluid leakage to the third spaces supported nephrotic syndrome diagnosis. The patient's condition deteriorated, leading to intensive care admission due to, hypertensive crisis, and respiratory distress. High total plasma homocysteine and low methionine levels raised suspicion of cobalamin metabolism disorders. Genetic testing confirmed biallelic MMACHC gene mutations, establishing the diagnosis of cblC defect. Treatment with hydroxycobalamin, folic acid, and betaine led to remarkable clinical improvement. DISCUSSION/CONCLUSION: This case underscores the significance of recognizing metabolic disorders like cblC defect in atypical presentations of nephrotic syndrome. Early diagnosis and comprehensive management are vital to prevent irreversible renal damage. While cblC defects are more commonly associated with atypical hemolytic uremic syndrome, this case highlights the importance of considering cobalamin defects in the differential diagnosis of nephrotic syndrome, especially when associated with accompanying findings such as hemolysis. Our case, which has one of the highest homocysteine levels reported in the literature, emphasizes this situation again.

Unilateral hypertensive choroidopathy as a sole manifestation in malignant hypertension: optical coherence tomography angiography findings-case report.

BACKGROUND: We present a case of hypertensive choroidopathy due to malignant hypertension with exudative retinal detachment as a sole finding. We use OCT- angiography for initial diagnosis and report findings from extensive follow up. CASE PRESENTATION: A 51-year-old female with no past medical history, presented to our clinic with painless loss of vision in her left eye. Fundus examination revealed only exudative retinal detachment in her left eye that was confirmed with Optical Coherence Tomography. Fluorescein angiography showed hyperfluorescent spots with leakage in late phases. OCTA manifested a focal dark area in the choriocapillaris slab corresponding to flow signal voids, signifying regions of non-perfusion. Her blood pressure was 220/120 mmHG. Complete blood work -up failed to reveal any other possible etiology. During follow-up period of 9 months blood pressure normalized, patient regained visual function and choriocapillaris perfusion was completely restored. DISCUSSIONS AND CONCLUSIONS: Hypertensive choroidopathy with exudative retinal detachment can be the only sign of malignant hypertension and no pre-existing history of a systemic disease is required in order to become apparent. OCTA reveals areas of non-perfusion at choriocapillaris level, proving that it is an essential tool in the diagnosis and follow up of patients with hypertensive choroidopathy. Finally, we propose that early diagnosis prevents permanent damage of the RPE and leads to complete choroidal remodeling and better visual outcomes.

Severe and malignant hypertension are common in primary atypical hemolytic uremic syndrome.

Malignant hypertension is listed among the causes of secondary thrombotic microangiopathy, but pathogenic mutations in complement genes have been reported in patients with hypertension-induced thrombotic microangiopathy. Here we investigated the frequency and severity of hypertension in 55 patients with primary atypical hemolytic uremic syndrome (aHUS). A genetic analysis was performed in all patients, and funduscopic examination was performed in all the patients with Grades 2 and 3 hypertension. A cohort of 110 patients with malignant hypertension caused by diseases other than aHUS served as control. Thirty-six patients with aHUS presented Grade 2 or Grade 3 hypertension and funduscopic examination showed malignant hypertension in 19. Genetic abnormalities in complement were found in 19 patients (37% among patients with malignant hypertension). Plasmapheresis was performed in 46 patients and 26 received eculizumab. Renal and hematological responses were significantly lower after plasmapheresis (24%) than after eculizumab (81%). Renal survival was significantly higher in patients treated with eculizumab (85% at one, three and five years) compared to patients who did not receive this treatment (54%, 46% and 41%), respectively. Response to eculizumab was independent of hypertension severity and the presence of complement genetic abnormalities. Among patients with malignant hypertension caused by other diseases the prevalence of thrombotic microangiopathy was very low (5%). Thus, severe and malignant hypertension are common among patients with aHUS and eculizumab treatment leads to a higher renal survival when compared to plasmapheresis. However, thrombotic microangiopathy is uncommon among patients presenting with malignant hypertension caused by diseases other than aHUS.

Malignant Hypertension Complicated By Renal Thrombotic Micro Angiopathy: Role Of Adam 13 Mutational Analyses.

We report a case of a 38-year-old U.A.E national who presented with malignant hypertension and features of thrombotic microangiopathy. He presented with oliguria, renal failure, thrombocytopenia and haemolytic anaemia. He required several sessions of renal replacement therapy. ADAM 13 mutational analysis was sent to differentiate Thrombotic micro angiopathy due to thrombotic thrombocytopenic purpura (TTP) or malignant hypertension. Renal biopsy revealed histopathological features of malignant arteriolar nephrosclerosis (MANS). Haemolytic parameters improved after control of blood pressure and he was subsequently discharged with early nephrology follow up.

A case report of malignant hypertension in a young woman.

BACKGROUND: Malignant hypertension is a condition characterized by severe hypertension and multi-organ ischemic complications. Albeit mortality and renal survival have improved with antihypertensive therapy, progression to end-stage renal disease remains a significant cause of morbidity and mortality. The underlying cause of malignant hypertension, which can be primary or secondary hypertension, is often difficult to identify and this can substantially affect the treatment outcomes, as we report here. CASE PRESENTATION: A 33-year-old woman presented with severe hypertension and acute renal failure. Initial evaluation demonstrated hyperreninemia with hyperaldosteronism and a possible renal artery stenosis at the contrast-enhanced CT scan. Although this data suggested the presence of a secondary form of hypertension, further exams excluded our first diagnosis of renal artery stenosis. Consequently, the patient did not undergo renal angiography (and the contrast media infusion associated with it), but she continued to be medically treated to achieve a tight blood pressure control. Our conservative approach was successful to induce renal function recovery over 2 years of follow-up. CONCLUSION: This case highlights the difficulty in differentiating between primary and secondary forms of malignant hypertension, particularly when the patient presents with acute renal failure. Clinicians should consider renal artery ultrasound as a first level diagnostic technique, given that the presentation of primary malignant hypertension can often mimic a renal artery stenosis. Secondly, adequate control of blood pressure is essential for kidney function recovery, although this may require a long time.

[HYPERTENSIVE CRISIS: MODERN VIEW OF THE PROBLEM AND OPTIMIZATION OF DIAGNOSTIC AND THERAPEUTIC MODALITIES].

The data collected by Burdenko Military Hospital indicate that in the 1980s hypertensive crisis (HC) occurred in roughly 30% of the patients with AH. This value fell down to 16% by 2012, with a rise in the number of uncomplicated crises from 46 to 62%. Analysis of the causes behind these changes showed that half of the patients simply experienced an elevated arterial pressure with minimal clinical symptoms. The decrease in the number of complicated cases from 54 to 39% is doubtful bearing in mind that ICD-10 gives the status of nosological entities to complications of hypertensive crisis (stroke, myocardial infarction, etc.) but not to the HC syndrome proper requiring urgent hospitalization; due to this hypertensive crisis itself tends to be disregarded and not included in statistics. HC with acute clinically significant lesions of target organs requires intensive care or resuscitation using infusion of vasodilators and loop diuretics to stabilize arterial pressure. In case of uncomplicted HC and aggravation of hypertensive disease, the medications of choice are oral short-acting ACE inhibitors and imidazoline receptor agonists.

Scleroderma renal crisis as an initial presentation of systemic sclerosis: a case report and review of the literature.

Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) that is characterised by new-onset malignant hypertension and progressive acute renal failure, often with associated microangiopathic haemolytic anaemia and thrombocytopenia. SRC was at one time almost uniformly fatal, with death often occurring within a few weeks. With the development of angiotensin-converting-enzyme inhibitors (ACE-I), survival has improved dramatically, but death rates still remain unacceptably high. About 20% of SRC cases occur prior to making a diagnosis of SSc and, in some cases, there is no evidence of skin sclerosis at the time that SRC develops. In this report, we present a case in which a patient developed SRC prior to being diagnosed with scleroderma. Additionally, we review the pathogenesis, presenting signs and symptoms, management and prognosis of SRC.

Catastrophic APS in the context of other thrombotic microangiopathies.

The catastrophic antiphospholipid syndrome (CAPS) is a rare disease that affects 1 % of cases with antiphospholipid syndrome (APS). CAPS can mimic or overlap with different thrombotic diseases; many patients present with a microthrombotic storm or thrombotic microangiopathic hemolytic anemia (TMHA). Thus, the differential diagnosis of CAPS includes thrombotic thrombocytopenic purpura (TTP), typical and atypical hemolytic uremic syndrome (HUS), systemic infections, malignancies, pregnancy-related disorders, malignant hypertension, heparin-induced thrombocytopenia, and drug-induced thrombotic microangiopathies. Antiphospholipid antibody (aPL) positivity has been proposed as the clue in this differential diagnosis; however, aPL can also occur in healthy people and in those with infections or malignancies. Thus, the differential diagnosis of an aPL-positive patient presenting with a microthrombotic storm is broad; the workup should include a special attention to signs of infection and disseminated malignant disease, assessing the funduscopic signs of malignant hypertension, testing ADAMTS13 activity and anti-heparin-platelet factor 4 (HPF4) antibodies, and searching previous exposure to certain drugs. This article aims to review the main diseases included in the differential diagnosis of CAPS in the context of other thrombotic microangiopathies.

Facial nerve palsy in a 3-year-old child with severe hypertension.

We report an interesting case of a child with new-onset malignant hypertension (HTN) associated with facial paralysis. A review of the medical literature on this association and discussion of diagnostic and management aspects are included.

[Hypertensive urgency and emergency]. / Hypertensive Krise.

European and North-American guidelines for the diagnosis and therapy of arterial hypertension refer to hypertensive crisis as an acute and critical increase of blood pressure>180/120 mmHg. Presence of acute hypertensive target organ damage, such as stroke, myocardial infarction or heart failure, in this situation defines a "hypertensive emergency". In these patients, immediate lowering of blood pressure (about 25% within one to two hours) in an intensive care setting is mandatory to prevent further progression of target organ damage. In contrast to hypertensive emergencies, hypertensive urgencies are characterized by an acute and critical increase in blood pressure without signs or symptoms of acute hypertensive target organ damage. In these patients, blood pressure should be lowered within 24 to 48 hours in order to avoid hypertensive target organ damage. In general, hospitalization is not required, and oral antihypertensive therapy usually is sufficient. However, further and continuing outpatient care has to be ensured.

Pulmonary renal syndrome secondary to malignant hypertension.

A man in his early 30s presented with sudden-onset respiratory distress, haemoptysis and reduced urine output. He was in volume overload with a blood pressure recording of 240/180 mm Hg. Pulmonary renal syndrome was suspected and he was initiated on plasmapheresis, followed by steroid pulse therapy. Chest radiography and the presence of fragmented red cells on the peripheral smear were unexplained. These were later explained by hypertensive nephropathy and thrombotic microangiopathy changes on renal biopsy. His respiratory and haematological parameters improved with blood pressure control. Malignant hypertension closely resembles pulmonary renal syndrome, which must be remembered in order to avoid plasmapheresis and high-dose immunosuppressive therapy.

A multi-centre case series of patients with coexistent intracranial hypertension and malignant arterial hypertension.

OBJECTIVE: To describe the clinical characteristics, outcomes, and management of a large cohort of patients with concomitant malignant arterial hypertension and intracranial hypertension. METHODS: Design: Retrospective case series. SUBJECTS: Patients aged ≥ 18 years with bilateral optic disc oedema (ODE), malignant arterial hypertension and intracranial hypertension at five academic institutions. Patient demographics, clinical characteristics, diagnostic studies, and management were collected. RESULTS: Nineteen patients (58% female, 63% Black) were included. Median age was 35 years; body mass index (BMI) was 30 kg/m2. Fourteen (74%) patients had pre-existing hypertension. The most common presenting symptom was blurred vision (89%). Median blood pressure (BP) was 220 mmHg systolic (IQR 199-231.5 mmHg) and 130 mmHg diastolic (IQR 116-136 mmHg) mmHg), and median lumbar puncture opening pressure was 36.5 cmH2O. All patients received treatment for arterial hypertension. Seventeen (89%) patients received medical treatment for raised intracranial pressure, while six (30%) patients underwent a surgical intervention. There was significant improvement in ODE, peripapillary retinal nerve fibre layer thickness, and visual field in the worst eye (p < 0.05). Considering the worst eye, 9 (47%) presented with acuity ≥ 20/25, while 5 (26%) presented with ≤ 20/200. Overall, 7 patients maintained ≥ 20/25 acuity or better, 6 demonstrated improvement, and 5 demonstrated worsening. CONCLUSIONS: Papilloedema and malignant arterial hypertension can occur simultaneously with potentially greater risk for severe visual loss. Clinicians should consider a workup for papilloedema among patients with significantly elevated blood pressure and bilateral optic disc oedema.

[Hypertensive crisis: pathogenesis, clinic, treatment].

Contemporary data on mechanisms of development, types, and clinical picture of hypertensive crisis (HC) are presented. Algorithms of rational therapy of uncomplicated and complicated HC are considered. Appropriateness of the use in HC of antihypertensive drugs with multifactorial action is stressed. These drugs include urapidil - an antihypertensive agent with complex mechanism of action. Blocking mainly the postsynaptic 1-adrenoreceptors urapidil attenuates vasoconstrictor effect of catecholamines and decreases total peripheral resistance. Stimulation of 5HT1-receptors of medullary vasculomotor center promotes lowering of elevated vascular tone and prevents development of reflex tachycardia.

[Severe hypertension: definition and patients profiles]. / Définition et profil des patients ayant une hypertension artéirielle sévere.

Severe arterial hypertension gathers relatively different clinical situations explained by the heterogeneity of the definitions of this clinical setting. From a medical point of view, severe hypertension is a short course situation defined by very high values of blood pressure corresponding to grade 3 hypertension. In France, until 2011, the social security also included in the definition of severe HTA chronic situations characterized by moderate blood pressure values requiring at least triple anthihypertensive therapies associated with a clinical or infraclinical target organ damages. These clinical profiles, much more frequent than grade 3 hypertension, allowed the full reimbursement of care costs for these patients. In France, it is estimated that 10% of hypertensive patients present a severe form with an annual incidence of 50,000 patients. The patients with severe hypertension have an increased cardiovascular morbidity justifying a closer clinical monitoring. From an economic point of view, these severe forms of hypertension have a higher cost of care, explained primarily by a more frequent need of specialized referrals, radiological exams and hospitalizations. This excess cost justified the existence of a full coverage of induced costs by the social security, since the incidence of severe hypertension is more frequent in the low social categories, and in patients with economic fragility.

[Management of hypertension recorded as at least 180/110 mmHg]. / Prise en charge d'une hypertensìon artérielle supérieure ou égale a 180/110 mmHg.

Stage 3 hypertension (severe) is far from rare. It may be part of a previous hypertension condition which is difficult to control, or occur more acutely, in which case it will be harder for the patient to bear. When it is symptomatic and a fortiorione or more organs targeted by hypertension are affected, management must be fast and appropriate. It may take the form of a hypertensive urgency, in which case the investigations and treatment usually take place in outpatients, with oral treatment. it may also be a hypertensive emergency for which treatment involves hospitalization in an intensive care unit with intravenous anti-hypertensive treatment. A reduction in blood pressure must be obtained rapidly but not suddenly; it must be more or less significant depending on the clinical situation, and also progressive.

[Management of resistant hypertension]. / Prise en charge d'une hypertension artérielle résistante.

High blood pressure is one of the leading factors influencing the cardiovascular risk. Despite current knowledge on the management of hypertension and the numerous antihypertensive drugs available, hypertension remains insufficiently controlled and part of these "uncontrolled" patients meet the definition of resistant hypertension. Resistant hypertension is defined by the failure of lowering blood pressure values to blood pressure target (office blood pressure < 140/90 or 130/80 mmHg in patients with diabetes or chronic kidney disease) despite appropriate treatment with optimal doses of three antihypertensive drugs from three different classes, one of which is a diuretic. Pseudoresistance should be excluded by using 24h ambulatory blood pressure or home blood pressure. The management of resistant hypertension includes the screening of secondary forms of hypertension and the identification of life style factors such as obesity, excessive alcohol and dietary sodium intake, volume overload, drug-induced hypertension. The treatment associates lifestyle changes, discontinuation of interfering substances, association of antihypertensive drugs on top of the initial triple therapy (including diuretic, blockers of the renin-angiotensin system and calcium channel blockers) ie aldosterone antagonists as fourth line treatment. New device-based approaches aiming to decrease the sympathetic tone including renal denervation and baroreceptor stimulation are under development.