This child's presentation of recurrent bacterial infections, severe periodontitis, and marked leukocytosis is consistent with leukocyte adhesion deficiency (LAD) LAD is caused by defective integrins on the leukocyte surface, which normally allow neutrophils to adhere to vascular endothelium, exit the vasculature, and migrate to areas of infection or inflammation.

Lack of neutrophil migration in LAD results in recurrent skin (eg, cellulitis, abscess, omphalitis) and mucosal (eg, periodontal) infections as well as poor wound healing. Examination shows inflammation with a notable lack of purulence. Biopsy of infected tissue is devoid of neutrophils and culture often grows Staphylococcus aureus or Gram-negative bacilli. Peripheral serum studies show marked leukocytosis and neutrophilia, particularly during episodes of infection. Classically, the first presenting sign of LAD is delayed umbilical cord separation (age >3 weeks).

(Choice A) Adenosine deaminase deficiency is an autosomal recessive form of severe combined immunodeficiency, which is characterized by deficient formation of mature B and T lymphocytes. Severe combined immunodeficiency presents with severe infections and failure to thrive. Laboratory studies show marked lymphopenia.

(Choice B) Patients with complement deficiencies are at increased risk for disseminated bacterial infections, particularly with encapsulated bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis). Cutaneous infections and neutrophilia are not seen.

(Choice C) Defective B lymphocyte maturation occurs in X-linked agammaglobulinemia (Bruton). Recurrent sinopulmonary and gastrointestinal infections with low B cell and immunoglobulin concentrations are typical. This female patient's history of periodontitis is inconsistent with X-linked agammaglobulinemia.

(Choice D) Chronic granulomatous disease (CGD) is a defect in intracellular killing due to impaired respiratory burst from activated phagocytes. Patients with CGD present with infections from catalase-positive organisms (eg, Staphylococcus aureus, Serratia marcescens, Burkholderia cepacia), Streptococcus pyogenesis catalase-negative and would be an unusual finding. In addition, patients with CGD do not have neutrophilia.

Educational objective:

Leukocyte adhesion deficiency presents with delayed umbilical cord separation, recurrent skin and mucosal bacterial infections (without purulence), and severe periodontal disease. Marked leukocytosis with neutrophil predominance is common.

A 49-year-old man comes to the emergency department with severe shortness of breath. The patient has a history of hypertension and medication nonadherence. Blood pressure is 260/144 mm Hg and pulse is 100/min. Chest examination demonstrates bibasilar crackles. There are no heart murmurs. Serum creatinine is 1.6 mg/dL. Intravenous furosemide and continuous nitroprusside infusion are started, along with noninvasive positive pressure ventilation, and he experiences improvement in his symptoms. The next morning, the patient is confused and lethargic, and he suffers a generalized tonic-clonic seizure. The skin appears flushed, and serum lactic acid level is elevated. The nitroprusside infusion rate was Kept higher !
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This patient's clinical presentation is consistent with cyanide toxicity from nitroprusside. Nitroprusside is a vasodilator with quick onset/offset kinetics commonly used for rapid blood pressure control in patients with hypertensive emergency. Nitroprusside [Na (CN),NO] rapidly decomposes to nitric oxide (NO: vasodilator) and cyanide ion (CN: toxin). Key risk factors for nitroprusside-induced cyanide toxicity include high doses, prolonged infusions, and renal insufficiency (eg, acute kidney injury due to hypertensive emergency).

Cyanide is a potent mitochondrial toxin that binds heme centers in cytochrome c oxidase (complex IV), blocking the electron transport chain. Because mitochondria are unable to reduce oxygen, venous blood returning from tissues remains saturated with oxygen and appears bright red. Loss of aerobic respiration also promotes lactic acidosis. As ATP is depleted, acute cyanide toxicity causes neurologic dysfunction (eg, altered mental status, seizures) and cardiovascular collapse.

Cyanide is cleared by rhodanese, an enzyme that transfers sulfur to cyanide to form thiocyanate (SCN) for excretion in urine. Because cyanide overdose depletes available sulfur donors, one approach to treatment is to provide additional sulfur groups with sodium thiosulfate. Other treatments include hydroxocobalamin (directly sequesters CN-) and sodium nitrite (induces methemoglobinemia to scavenge CN-).

(Choice A) Methemoglobinemia, caused by oxidizing agents (eg, nitrites, chloroquine), and carbon monoxide exposure increase hemoglobin's affinity for oxygen, which impairs oxygen unloading into the tissues. Both processes disrupt peripheral tissue oxygen delivery, leading to lactic acidosis.

(Choice B) Arsenic inhibits pyruvate dehydrogenase, the rate-limiting enzyme governing conversion of pyruvate to acetyl-CoA for entry into the tricarboxylic acid cycle, causing depletion of ATP. Acute arsenic poisoning presents with severe enteritis (diarrhea) and neurologic dysfunction

(Choice C) Ethanol is converted to acetaldehyde by alcohol dehydrogenase, with concurrent reduction of NAD+ to NADH. High NADH levels subsequently cause feedback inhibition of lactate dehydrogenase (hepatic
gluconeogenesis enzyme), leading to hypoglycemia and lactic acidosis.

Choice E) Electron transport uncouplers (eg, dinitrophenol [DNP]) cause protons to back-leak across mitochondrial membrane, dissipating the gradient as wasted heat instead of generating ATP. Because metabolic rate, these agents are occasionally abused as catabolic weight loss agents. Accidental overdose
results in fatal hyperthermia.


Take Home Point

Cyanide Toxicity an important adverse effect of nitroprusside. Blockage of ETC leads to impaired oxygen utilization, causing lactic acidosis, neurologic dysfunction, and cardiovascular collapse.

A 73-year-old man with dementia is brought to the emergency department by nursing home staff because he has been moaning continuously and gripping his lower abdomen for the past 36 hours. The patient is unable to give any history, but staff members say that he refused oral intake the previous day. He has had no vomiting or diarrhea. His last bowel movement was 2 days ago. The patient uses adult diapers, which were last changed 2 days ago. He has a history of benign prostatic hyperplasia, external hemorrhoids, hypertension, and hyperlipidemia. One year ago, he was hospitalized for diverticular bleeding that resolved spontaneously. His medications review shows that his primary care physician started amitriptyline 8 days ago for chronic neck pain. On physical examination, the patient is afebrile. His blood pressure is 160/70 mm Hg and his pulse is 100/min. The mucous membranes are moist. His lung fields are clear to auscultation. Palpation of the abdomen shows fullness and tenderness along the midline below the umbilicus without guarding or rigidity. Bowel sounds are heard in all 4 quadrants.
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#INTREGRATED #BTR

This patient's clinical presentation is sufficient to initiate prompt urinary catheterization for suspected urinary retention. Bedside ultrasound or bladder scan (if available) can also help in diagnosis but should not delay urinary catheterization. Urinary catheterization can document a postvoid residual bladder volume (>50 mL is considered diagnostic for urinary retention) and provides symptomatic relief by draining urine from the distended bladder. This patient should also discontinue amitriptyline therapy.

(Choice A) An abdominal CT scan would reveal a distended bladder in this patient and may also show hydronephrosis and hydroureter However, CT scans are more expensive and time-consuming than urinary catheterization and will not provide symptomatic relief.

Choice B) Upright abdominal x-ray is not as reliable for evaluating urinary retention as it may not show a distended bladder (unless obstructed by a bladder stone). Abdominal x-rays are more useful for diagnosing ileus or small-bowel obstruction. Amitriptyline may cause ileus, but these patients typically develop nausea, vomiting, hypoactive bowel sounds, distended abdomen, diffuse mild abdominal pain, and abdominal imaging showing dilated bowel loops without air/fluid levels. This patient's normal bowel sounds, infraumbilical fullness, and lack of wet diapers for 2 days make urinary retention more likely than ileus.


(Choice C) Intravenous fluids, analgesics, and observation are the treatment for nephrolithiasis (kidney stones). Patients with kidney stones typically present with intense flank pain and hematuria instead of suprapubic fullness. Intravenous fluids could potentially worsen this patient's obstructive urinary symptoms.



Take Home Point
Drugs with anticholinergic properties can cause acute urinary retention by preventing detrusor muscle contraction and urinary sphincter relaxation. The treatment involves urinary catheterization and discontinuing the medication.

40-year-old woman is brought to the emergency department due to difficulty breathing and muscle weakness. She was one of several people who developed symptoms in a movie theater. Temperature is 36.7 C (98.1 F), blood pressure is 112/62 mm Hg, pulse is 51/min, and respirations are 24/min. On physical examination, the patient is diaphoretic. The pupils are pinpoint and unreactive, and significant tearing is noted. Diffuse rhonchi and wheezing are present in the lungs bilaterally. Muscle strength is diminished throughout, and fasciculations are noted in the extremities. First-line therapy is administered, but the patient remains weak.
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This patient with bradycardia, miosis, diaphoresis, excessive secretions (eg, bronchonhea, tearing), and weakness with fasciculations has signs of cholinergic toxicity. Most cases of cholinergic toxicity are due to organophosphate pesticides. However, the occurrence in multiple patients in a city setting suggests intentional organophosphate exposure, possibly due to a chemical weapon (eg, sarin, soman).

Organophosphates inhibit acetylcholinesterase in the muscarinic and nicotinic cholinergic synapses, leading to decreased acetylcholine degradation and overstimulation of the corresponding receptors. In addition to widespread increased visceral smooth muscle tone and glandular secretions due to muscarinic hyperactivity (mnemonic: DUMBELLS), nicotinic hyperactivity causes muscle weakness and paralysis that can lead to rapid respiratory depression and death.

Initial management of organophosphate toxicity includes atropine, a competitive inhibitor of acetylcholine at the muscarinic receptor, which relieves muscarinic hyperstimulation. However, atropine does not have activity at the nicotinic receptors and cannot treat neuromuscular dysfunction. Therefore, pralidoxime, a cholinesterase- reactivating agent that works at both nicotinic and muscarinic sites, should be administered to any patient with neuromuscular dysfunction (eg, weakness, fasciculations). It should be given only after atropine because

pralidoxime can cause transient acetylcholinesterase inhibition, which can momentarily worsen symptoms

(Choice A) Diphenhydramine is an inverse agonist of the histamine H1 receptor, which allows it to function as an antihistamine. Because the H1 receptor is similar to the muscannic receptor, diphenhydramine has some antimuscarinic effects (eg, urinary retention). However, it is less potent than atropine, and it would not reverse nicotinic dysfunction (weakness).

(Choice B) Hemodialysis is sometimes used to treat toxic alcohol poisoning, which usually presents with altered mental status, as well as vision changes (methanol) or flank pain and hematuria (ethylene glycol) It is not Indicated in cholinergic toxicity

Choice C) Hyperbaric oxygen is used to treat severe carbon monoxide poisoning, which presents with nausea, dizziness, and altered mental status. Patients typically have cherry-red cheeks and lips.

(Choice D) Physostigmine is an acetylcholinesterase inhibitor that is sometimes used to treat anticholinergic toxicity (le, flushing, mydriasis, anhidrosis, fever, urinary retention). It would worsen this patient's symptoms.

Educational objective:

Organophosphates inhibit acetylcholinesterase, leading to symptoms of muscarinic (mnemonic: DUMBELLS) and nicotinic (neuromuscular dysfunction) cholinergic hyperstimulation. Management includes atropine, a competitive inhibitor of acetylcholine at the muscarinic receptor (reverses muscarinic symptoms), followed by pralidoxime, a cholinesterase-reactivating agent that treats both nicotinic and muscarinic symptoms

A 27-year-old man comes to the office due to a 2-week history of genital papules that are not painful or pruritic. Over this period, he has also had fatigue and mild, generalized arthralgia but no urethral discharge or dysuria. The patient had gonococcal urethritis 3 months ago, which was adequately treated, and tests for other sexually transmitted infections at that time were negative. He is sexually active with several male and female partners and reports using condoms consistently after the episode of gonorrhea. Temperature is 37.6 C (99.6 F). Physical examination shows a faint, diffuse maculopapular skin rash involving the trunk, extremities, palms, and soles. There are several enlarged, nontender inguinal lymph nodes. Genital examination reveals multiple, raised, wart-like skin lesions on the scrotum and perineal region.
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Syphilis manifestations

Primary- Painless genital ulcer (chancre)

secondary- Diffuse rash (palms & soles) ,Lymphadenopathy (epitrochlear),
Condyloma latum,Oral lesions,Hepatitis

Latent-Asymptomatic

Tertiary-CNS (tabes dorsalis, dementia)
• Cardiovascular (aortic aneurysm/insufficiency)
Cutaneous (gummas)

Secondary syphilis is characterized by the spread of the causative spirochete, Treponema pallidum, through the blood to the skin and mucosal surfaces. Patients usually have a diffuse maculopapular skin rash that includes the palms and soles. They may also develop condylomata lata, which are painless, wart-like, elevated plaques, on moist areas of the skin such as the scrotum and perineum. Lymphadenopathy, fatigue, arthralgias, and mild fever are also common. Histopathologic examination of syphilitic lesions (at all stages) classically demonstrates proliferative endarteritis of small vessels with a surrounding plasma cell-rich infiltrate.

This patient was likely infected with syphilis at the same time he was infected with gonorrhea (coinfection is common). Serologic testing for syphilis (eg, rapid plasma reagin) is often falsely negative in early infection due to lag time between acquisition of T pallidum and the development of a measurable humoral antibody response. Patients who do not notice or ignore the genital chancre of primary syphilis often develop secondary syphilis 2-10 weeks later.

Secondary syphilis is characterized by the spread of the causative spirochete, Treponema pallidum, through the blood to the skin and mucosal surfaces. Patients usually have a diffuse maculopapular skin rash that includes the palms and soles. They may also develop condylomata lata, which are painless, wart-like, elevated plaques, on moist areas of the skin such as the scrotum and perineum. Lymphadenopathy, fatigue, arthralgias, and mild fever are also common. Histopathologic examination of syphilitic lesions (at all stages) classically demonstrates proliferative endarteritis of small vessels with a surrounding plasma cell-rich infiltrate.

This patient was likely infected with syphilis at the same time he was infected with gonorrhea (coinfection is common). Serologic testing for syphilis (eg, rapid plasma reagin) is often falsely negative in early infection due to lag time between acquisition of T pallidum and the development of a measurable humoral antibody response. Patients who do not notice or ignore the genital chancre of primary syphilis often develop secondary syphilis 2-10 weeks later.

(Choice A) Pemphigus vulgaris is characterized by autoantibodies against epithelial cell surface antigens, leading to the formation of mucous membrane blisters that quickly erode; histopathology usually shows acantholysis (detached keratinocytes) with superficial dermal infiltrate.

(Choice B) Kaposi sarcoma (KS) lesions appear as whirls of dysplastic spindle-shaped cells surrounding areas of angioproliferation. KS is due to human herpesvirus 8 infection and most commonly occurs in the setting of advanced AIDS. Lesions typically appear as purplish or dark brown plaques and nodules on the lower extremities.

(Choice D) Biopsy of erythema nodosum lesions usually reveals septal panniculitis with multinucleated giant cells. Erythema nodosum is a delayed-type hypersensitivity reaction that can occur due to drugs or other antigenic stimuli. Patients usually present with tender nodules on the bilateral shins.

(Choice E) Biopsy of anogenital warts will demonstrate papillomatous epidermal hyperplasia with cytoplasmic vacuolization. Anogenital warts are caused by specific serotypes of human papillomavirus (eg, HPV-6, HPV-11). Anogenital warts are not typically associated with diffuse maculopapular rash or systemic symptoms.
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A 39-year-old woman, gravida 1 para 1, comes to the office due to breast pain. She had an uncomplicated vaginal delivery a week ago and is breastfeeding her infant. Four days ago, the patient began to have bilateral nipple soreness with breastfeeding. However, for the past few days, the pain has worsened, is present between feeds, and has prevented breastfeeding. She has also developed bloody nipple discharge. The patient's pregnancy was complicated by gestational diabetes mellitus, but otherwise, she has no chronic medical conditions. Temperature is 37.5 C (99.5 F). Bilateral nipples and areolae have open, bloody, linear abrasions. The breasts are diffusely engorged and mildly tender to palpation, but there are no palpable masses or lymphadenopathy. The remainder of the examination is unremarkable.
#INICET #NEETPG26

Proper breastfeeding technique promotes maternal comfort, ensures adequate infant nutritional intake, and facilitates long-term breastfeeding.

Most breastfeeding patients experience nipple pain in the immediate postpartum period as they become accustomed to nursing 8-12 times/day or more, but this typically resolves after a few weeks. Nipple pain that worsens and persists between feedings is commonly due to nipple injury caused by poor infant positioning and improper latch-on technique. On examination, patients can have open, linear areolar abrasions that cause a bloody-appearing nipple discharge, bruising, cracking, and blistering may also be present. Breast engorgement, as seen in this patient with bilateral, diffusely tender, and engorged breasts, can also develop because nipple pain limits breastfeeding.

Initial management is with the observation of breastfeeding and patient education. Nipple injury is a significant risk factor for multiple adverse outcomes (eg, plugged milk ducts, mastitis, breast abscess), which often lead to premature cessation of breastfeeding.

(Choice A) Lactational mastitis is caused by bacterial overgrowth of stagnant milk in blocked ducts; it is a common cause of breast pain in breastfeeding patients. In contrast to this patient, those with lactational mastitis typically have fever and localized warmth or erythema over a single breast.

(Choice B) Candida mastitis can be caused by spread from infant oral flora. Patients typically have nipple pain that radiates across the breast with latching; however, the pain is described as sharp and shooting and is usually out of proportion to the examination. In addition, it is typically unilateral, and the affected breast often has flaky, scaling skin over the nipple.

(Choice C) Inflammatory breast cancer can cause unilateral, not bilateral, breast pain and tenderness. Patients typically have a breast mass with associated skin thickening and erythema (peau d'orange appearance) with axillary lymphadenopathy, which is not seen in this patient.

(Choice D) An intraductal papilloma, a papillary tumor involving the breast duct, typically presents with bloody nipple discharge but no associated breast pain.

TAKE HOME POINT

Persistent nipple pain with breastfeeding is typically due to nipple injury, which can present with bilateral nipple abrasions and bloody nipple discharge. The most common underlying causes are poor infant positioning and improper latch-on technique.

A 35-year-old man comes to the office due to a progressive increase in breast size over the past 6 months. He is sexually active, has no chronic medical conditions, and takes no medications. The patient does not use tobacco, alcohol, or illicit drugs. Vital signs are normal. BMI is 28 kg/m². Gynecomastia with mild bilateral breast tenderness is present. Genitourinary examination reveals a 1-cm nodule in the right testis. The examination is otherwise normal. Laboratory results are as follows:
LH: 3 U/L (normal: 6–23 U/L)
FSH: 2 U/L (normal: 4–25 U/L)
Testosterone: 270 ng/dL (normal: 300–1,000 ng/dL)
Estradiol: 115 pg/mL (normal: 20–60 pg/mL)
β-hCG: undetectable
Alpha-fetoprotein: undetectable