Understanding Nephrotic Syndrome and Nephritic Syndrome

Nephrotic syndrome is a condition characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. On the other hand, nephritic syndrome is defined by azotemia, hematuria, hypertension, and oliguria. Both syndromes present with edema, but the amount of proteinuria is higher in nephrotic syndrome.

In nephrotic syndrome, the glomerulus has small pores that allow protein to pass through but not cells, resulting in proteinuria and hypoalbuminemia. The liver compensates for protein loss by increasing the synthesis of albumin, LDL, VLDL, and lipoprotein(a), leading to lipid abnormalities. Patients with nephrotic syndrome are also at risk of hypercoagulability and infection due to the loss of inhibitors of coagulation and immunoglobulins in the urine.

The etiology of nephrotic syndrome varies depending on age and comorbidities. Minimal change disease is the most common cause in children, while focal segmental glomerulosclerosis is the most common cause in younger adults. Membranous nephropathy is the most common cause in older people, and diabetic nephropathy in adults with long-standing diabetes. Secondary causes include amyloidosis, lupus nephritis, and multiple myeloma.

Categorizing glomerular renal disease into syndromes such as nephrotic syndrome and nephritic syndrome helps narrow the differential diagnosis. Understanding the differences between these two syndromes is crucial in the diagnosis and management of glomerular renal disease.

The correct term is tardive dyskinesia, which is characterized by abnormal involuntary choreoathetoid movements that occur late in patients who have been on conventional antipsychotics. Symptoms may include lip-smacking, jaw pouting, chewing, repetitive blinking, or tongue poking. This condition is often difficult to treat, but replacing the antipsychotic or trying tetrabenazine may provide some relief.

Parkinsonism, which can also occur in patients taking conventional antipsychotics, presents with symptoms similar to those of Parkinson’s disease, such as tremor, blank facies, bradykinesia, and muscle rigidity. However, this option is incorrect as there is no mention of other symptoms in the stem, and repetitive blinking is not a typical symptom of Parkinsonism.

While dry eyes may lead to eye twitching, repetitive blinking is unlikely, and other symptoms such as visual disturbance or watering of the eyes would be expected.

Sjogren’s syndrome, which can cause dry eyes, is also an unlikely cause of repetitive involuntary blinking.

Blepharospasm, which is characterized by involuntary twitching or contraction of the eyelid, is a focal dystonia that may last only a few days or be lifelong. While stress or fatigue may trigger it, the patient in the stem is more likely suffering from tardive dyskinesia due to extrapyramidal side effects of chlorpromazine, a typical antipsychotic.

Antipsychotics are a type of medication used to treat schizophrenia, psychosis, mania, and agitation. They are divided into two categories: typical and atypical antipsychotics. The latter were developed to address the extrapyramidal side-effects associated with the first generation of typical antipsychotics. Typical antipsychotics work by blocking dopaminergic transmission in the mesolimbic pathways through dopamine D2 receptor antagonism. However, they are known to cause extrapyramidal side-effects such as Parkinsonism, acute dystonia, akathisia, and tardive dyskinesia. These side-effects can be managed with procyclidine. Other side-effects of typical antipsychotics include antimuscarinic effects, sedation, weight gain, raised prolactin, impaired glucose tolerance, neuroleptic malignant syndrome, reduced seizure threshold, and prolonged QT interval. The Medicines and Healthcare products Regulatory Agency has issued specific warnings when antipsychotics are used in elderly patients due to an increased risk of stroke and venous thromboembolism.

According to the 2005 NICE Guidance on the treatment of obsessive-compulsive disorder and body dysmorphic disorder, adults with OCD should be prescribed one of the following SSRIs as their first pharmacological treatment: fluoxetine, fluvoxamine, paroxetine, sertraline, or citalopram.

Understanding Obsessive-Compulsive Disorder (OCD)

Obsessive-compulsive disorder (OCD) is a mental health condition that affects 1 to 3% of the population. It is characterized by the presence of obsessions, which are unwanted intrusive thoughts, images, or urges, and compulsions, which are repetitive behaviors or mental acts that a person feels driven to perform. These symptoms can cause significant functional impairment and distress.

Risk factors for OCD include a family history of the condition, age (with peak onset between 10-20 years), pregnancy/postnatal period, and a history of abuse, bullying, or neglect.

The management of OCD involves classifying the level of impairment as mild, moderate, or severe using the Y-BOCS scale. For mild impairment, low-intensity psychological treatments such as cognitive behavioral therapy (CBT) including exposure and response prevention (ERP) are recommended. If this is insufficient, a course of an SSRI or more intensive CBT (including ERP) can be offered. For moderate impairment, a choice of either an SSRI or more intensive CBT (including ERP) is recommended, with clomipramine as an alternative first-line drug treatment to an SSRI if necessary. For severe impairment, referral to the secondary care mental health team for assessment is necessary, with combined treatment of an SSRI and CBT (including ERP) or clomipramine as an alternative while awaiting assessment.

ERP is a psychological method that involves exposing a patient to an anxiety-provoking situation and stopping them from engaging in their usual safety behavior. This helps them confront their anxiety, leading to the eventual extinction of the response. Treatment with an SSRI should continue for at least 12 months to prevent relapse and allow time for improvement. Compared to depression, the SSRI usually requires a higher dose and a longer duration of treatment (at least 12 weeks) for an initial response.

If a person requires assistance with insulin injections, insulin detemir or insulin glargine may be used instead of NPH insulin to reduce the frequency of injections from twice to once daily. Additionally, if the person experiences recurrent symptomatic hypoglycemic episodes or would need twice-daily NPH insulin injections in combination with oral antidiabetic drugs, insulin detemir or insulin glargine should be considered as an alternative. These insulin options may be administered separately or as a pre-mixed (biphasic) human insulin preparation.

NICE has updated its guidance on the management of type 2 diabetes mellitus (T2DM) in 2022 to reflect advances in drug therapy and improved evidence regarding newer therapies such as SGLT-2 inhibitors. For the average patient taking metformin for T2DM, lifestyle changes and titrating up metformin to aim for a HbA1c of 48 mmol/mol (6.5%) is recommended. A second drug should only be added if the HbA1c rises to 58 mmol/mol (7.5%). Dietary advice includes encouraging high fiber, low glycemic index sources of carbohydrates, controlling intake of saturated fats and trans fatty acids, and initial target weight loss of 5-10% in overweight individuals.

Individual HbA1c targets should be agreed upon with patients to encourage motivation, and HbA1c should be checked every 3-6 months until stable, then 6 monthly. Targets should be relaxed on a case-by-case basis, with particular consideration for older or frail adults with type 2 diabetes. Metformin remains the first-line drug of choice, and SGLT-2 inhibitors should be given in addition to metformin if the patient has a high risk of developing cardiovascular disease (CVD), established CVD, or chronic heart failure. If metformin is contraindicated, SGLT-2 monotherapy or a DPP-4 inhibitor, pioglitazone, or sulfonylurea may be used.

Further drug therapy options depend on individual clinical circumstances and patient preference. Dual therapy options include adding a DPP-4 inhibitor, pioglitazone, sulfonylurea, or SGLT-2 inhibitor (if NICE criteria are met). If a patient doesn’t achieve control on dual therapy, triple therapy options include adding a sulfonylurea or GLP-1 mimetic. GLP-1 mimetics should only be added to insulin under specialist care. Blood pressure targets are the same as for patients without type 2 diabetes, and ACE inhibitors or ARBs are first-line for hypertension. Antiplatelets should not be offered unless a patient has existing cardiovascular disease, and only patients with a 10-year cardiovascular risk > 10% should be offered a statin.

According to the NICE guidelines on cervical cancer screening, if an individual’s second repeat smear at 24 months is still positive for high-risk human papillomavirus (hrHPV), they should be referred for colposcopy. Prior to this, if an individual is positive for hrHPV but receives a negative cytology report, they should have the HPV test repeated at 12 months. If the HPV test is negative at 12 months, they can return to routine recall. However, if they remain hrHPV positive and cytology negative at 12 months, they should have a repeat HPV test in a further 12 months. If they become hrHPV negative at 24 months, they can safely return to routine recall.

Understanding Cervical Cancer Screening Results

The cervical cancer screening program has evolved significantly in recent years, with the introduction of HPV testing allowing for further risk stratification. The NHS now uses an HPV first system, where a sample is tested for high-risk strains of human papillomavirus (hrHPV) first, and cytological examination is only performed if this is positive.

If the hrHPV test is negative, individuals can return to normal recall, unless they fall under the test of cure pathway, untreated CIN1 pathway, or require follow-up for incompletely excised cervical glandular intraepithelial neoplasia (CGIN) / stratified mucin producing intraepithelial lesion (SMILE) or cervical cancer. If the hrHPV test is positive, samples are examined cytologically, and if the cytology is abnormal, individuals will require colposcopy.

If the cytology is normal but the hrHPV test is positive, the test is repeated at 12 months. If the repeat test is still hrHPV positive and cytology is normal, a further repeat test is done 12 months later. If the hrHPV test is negative at 24 months, individuals can return to normal recall, but if it is still positive, they will require colposcopy. If the sample is inadequate, it will need to be repeated within 3 months, and if two consecutive samples are inadequate, colposcopy will be required.

For individuals who have previously had CIN, they should be invited for a test of cure repeat cervical sample in the community 6 months after treatment. The most common treatment for cervical intraepithelial neoplasia is large loop excision of transformation zone (LLETZ), which may be done during the initial colposcopy visit or at a later date depending on the individual clinic. Cryotherapy is an alternative technique.

Scabies: Causes, Symptoms, and Treatment

Scabies is a skin condition caused by the mite Sarcoptes scabiei, which is spread through prolonged skin contact. It is most commonly seen in children and young adults. The mite burrows into the skin, laying its eggs in the outermost layer. The resulting intense itching is due to a delayed hypersensitivity reaction to the mites and eggs, which occurs about a month after infection. Symptoms include widespread itching, linear burrows on the fingers and wrists, and secondary features such as excoriation and infection.

The first-line treatment for scabies is permethrin 5%, followed by malathion 0.5% if necessary. Patients should be advised to avoid close physical contact until treatment is complete and to treat all household and close contacts, even if asymptomatic. Clothing, bedding, and towels should be laundered, ironed, or tumble-dried on the first day of treatment to kill off mites. The insecticide should be applied to all areas, including the face and scalp, and left on for 8-12 hours for permethrin or 24 hours for malathion before washing off. Treatment should be repeated after 7 days.

Crusted scabies, also known as Norwegian scabies, is a severe form of the condition seen in patients with suppressed immunity, particularly those with HIV. The skin is covered in hundreds of thousands of mites, and isolation is essential. Ivermectin is the treatment of choice.

Obstetric cholestasis is the primary cause of itch during pregnancy that is not accompanied by a rash. To diagnose obstetric cholestasis, doctors should look for symptoms such as itchiness that begins in the third trimester, starts on the palms and soles before spreading upwards, worsens at night, and causes severe scratching that leads to excoriation marks. Additionally, patients may report anorexia, malaise, and abdominal pain, which are also associated with obstetric cholestasis.

If a woman displays any of these symptoms, it is recommended that she be admitted to the hospital or referred to an obstetrician on the same day. In secondary care, liver function tests are conducted to confirm the diagnosis, and treatment may include ursodeoxycholic acid and sedating antihistamines.

Jaundice During Pregnancy

During pregnancy, jaundice can occur due to various reasons. One of the most common liver diseases during pregnancy is intrahepatic cholestasis of pregnancy, which affects around 1% of pregnancies and is usually seen in the third trimester. Symptoms include itching, especially in the palms and soles, and raised bilirubin levels. Ursodeoxycholic acid is used for symptomatic relief, and women are typically induced at 37 weeks. However, this condition can increase the risk of stillbirth.

Acute fatty liver of pregnancy is a rare complication that can occur in the third trimester or immediately after delivery. Symptoms include abdominal pain, nausea, vomiting, headache, jaundice, and hypoglycemia. ALT levels are typically elevated. Supportive care is the initial management, and delivery is the definitive management once the patient is stabilized.

Gilbert’s and Dubin-Johnson syndrome may also be exacerbated during pregnancy. Additionally, HELLP syndrome, which stands for Haemolysis, Elevated Liver enzymes, Low Platelets, can also cause jaundice during pregnancy. It is important to monitor liver function tests and seek medical attention if any symptoms of jaundice occur during pregnancy.

Identifying Seborrhoeic Dermatitis: A Comparison with Other Skin Conditions

Seborrhoeic dermatitis is a common skin condition that produces a scaled rash. However, it can be difficult to distinguish from other skin conditions that also produce scaling lesions. Here, we compare seborrhoeic dermatitis with psoriasis, atopic eczema, folliculitis, and tinea capitis to help identify the key features of each condition.

Seborrhoeic dermatitis is characterized by a poorly defined rash, greasy skin, and a specific distribution pattern. Psoriasis, on the other hand, produces well-defined plaques and doesn’t typically involve greasy skin. Atopic eczema produces dry, scaling skin and often affects flexural sites, whereas folliculitis is inflammation of the hair follicles and doesn’t typically involve greasy skin. Tinea capitis, which causes hair loss and scaling of the skin, is less likely in this case as there is no hair loss present.

By comparing the key features of each condition, it becomes clear that the greasy skin and distribution pattern make seborrhoeic dermatitis the most likely diagnosis.

The Impact of CYP Inducers on Medications: A Case Study

CYP inducers can have a significant impact on medications that are metabolized by cytochrome P450 enzymes. In the case of carbamazepine and ciclosporin, carbamazepine’s induction of the enzymes would increase the rate of metabolism of ciclosporin, potentially leading to decreased plasma levels and serious implications due to ciclosporin’s narrow therapeutic window. Paracetamol is also metabolized by CYP, and while it is not contraindicated with carbamazepine, the production of a hepatotoxic metabolite may be relevant in cases of overdose. Lithium, on the other hand, is excreted renally, so induction of P450 enzymes would not alter its excretion rate, but changes in renal function could still impact its plasma level. Penicillins have a wide therapeutic index, so the impact of CYP inducers or inhibitors is not significant. As for salicylate, there is currently no listed interaction with carbamazepine, making it unlikely to cause any issues in this patient.

According to current NICE guidelines, patients with gout who experience two or more attacks per year should receive urate-lowering therapy (ULT). When starting ULT, it is recommended to also prescribe colchicine cover for up to six months. If colchicine is not suitable, an alternative option is to consider NSAID cover.

While high-dose prednisolone can effectively treat acute gout, low-dose prednisolone is not recommended for gout prevention due to the negative effects of long-term corticosteroid use.

Although NSAIDs like naproxen or ibuprofen can be used to treat gout, this may not be the best option for someone with a history of hiatus hernia. Unlike xanthine oxidase inhibitors such as allopurinol or febuxostat, NSAIDs are not considered ULT and are therefore not suitable for gout prevention.

Gout is caused by chronic hyperuricaemia and is managed acutely with NSAIDs or colchicine. Urate-lowering therapy (ULT) is recommended for patients with >= 2 attacks in 12 months, tophi, renal disease, uric acid renal stones, or prophylaxis if on cytotoxics or diuretics. Allopurinol is first-line ULT, with a delayed start recommended until inflammation has settled. Lifestyle modifications include reducing alcohol intake, losing weight if obese, and avoiding high-purine foods. Other options for refractory cases include febuxostat, uricase, and pegloticase.