Journal scan: A review of images in clinical medicine of immediate clinical significance, harvested from major international journals

From the desk of the Editor-in-chief

(1). Spontaneous Coronary-Artery Dissection

Abstract

A 32-year-old woman presented with severe chest pain. An ECG showed ST-segment elevations. Coronary angiography showed an abrupt caliber change in the right coronary artery

(2). Pleural Plaques from Secondhand Asbestos Exposure

Abstract

An 80-year-old woman had pleural plaques seen on chest radiographs. As a child, she had played with her father after he returned home from work with his clothing covered in “snow-like” particles.

(3). Eyelid Ecchymoses and Subconjunctival Hemorrhage in Pertussis

Abstract

A 10-year-old boy was brought to the ED with a 4-day history of progressive bruising of the eyelids. Four weeks before presentation, a dry cough had developed that had increased in intensity over the previous week.

(4). Oral Hairy Leukoplakia

Abstract

A 38-year-old man with a history of kidney transplantation presented with a 2-week history of burning, hairy lesions on his tongue. Examination revealed elongated, discolored papillae on the tongue.

(5). Sitosterolemia with Orbital Xanthogranulomas

Abstract

A 50-year-old woman presented with a 5-year history of xanthogranulomas under her eyes. Laboratory studies were notable for thrombocytopenia and very high levels of low-density lipoprotein cholesterol.

(6). Saving a Life by Recognizing the Rash: Niacin (Vitamin B3) Deficiency in Hartnup Disease With a Clinical Debut in Adulthood

Melanie Hafdi , Publication: Annals of Internal Medicine: Clinical Cases,Volume 3, Number 12,https://doi.org/10.7326/aimcc.2024.0137

Abstract

Tryptophan deficiency can lead to a critical shortness of niacin (vitamin B3), causing photosensitive dermatitis and a range of neurologic symptoms. The most common cause is severe protein malnutrition. However, in the case we present here, it is caused by a rare genetic disorder (Hartnup disease). A previously healthy 26-year-old woman presented with a photosensitive skin rash, myoclonic twitching of hands and mouth, and, ultimately, coma and status epilepticus. Starting treatment with high-dose niacin, even before the suspected diagnosis was confirmed, turned out to be a lifesaving intervention.

Background

Vitamin deficiencies may lead to neurologic impairment. Early recognition of these deficiencies is imperative because this impairment can be life-threatening and early treatment may lead to complete recovery.

Objective

Our objective is to describe the disease course of niacin (vitamin B3) deficiency caused by Hartnup disease.

Case Report

A 26-year-old woman was transferred to our tertiary care facility with a decreased level of consciousness. Her medical history reported recurrent urinary tract infections and a dysplastic left kidney. Three months prior, she presented with progressive fatigue and short-lasting episodes of diplopia and dysphagia. Over two to three weeks, her symptoms progressed and skin rash appeared on the back of her hands and face. One week before transfer to our facility, she developed visual and auditory hallucinations and levels of consciousness decreased. Magnetic resonance imaging showed hyperintensities of the cerebral cortex and caudate nuclei on diffusion weighted images (Figure 1). Cerebrospinal fluid analysis was normal and a regimen of intravenous methylprednisolone and immunoglobins for autoimmune encephalitis was started.

Fig (1). Skin manifestations (A) and magnetic resonance images (B) of the presented patient. A. Skin rash on admission and after 6 days of nicotinamide supplementation. Top: Before start of nicotinamide supplementation. Bottom: After 6 days of nicotinamide supplementation.

B. Magnetic resonance imaging showed hyperintensities of the cerebral cortex and caudate nuclei on diffusion trace images. Left to right: T2-weighted image, diffusion trace image, apparent diffusion coefficient.

Upon arrival, she opened her eyes, flexed her arms to pain, and made incomprehensible sounds. There was divergence of the eyes, with periorbital myoclonic twitching, myoclonic jerks of the fingers, symmetrical hyperreflexia, and bilateral Babinski signs. On her chin, perioral area, nose, glabella, forehead, and dorsum of the hands and feet there were moderately sharply demarcated erythematosquamous and crusted plaques in a typical photodistribution (Figure 1). Skin biopsy showed hyperparakeratosis of the stratum corneum and vacuolar changes of the basal epidermal layer. The diagnosis of pellagra (niacin deficiency) was considered. Her condition further deteriorated, with decreasing level of consciousness (no eye opening, slight withdrawal on pain, no verbal response), and she developed jaw clenching. Electroencephalography showed generalized spike-wave complexes in the frontal areas suggestive for epilepsy. She was intubated and treated with levetiracetam. High-dose nicotinamide was started (300 mg loading dose, followed by 250 mg three times daily). Clinical improvement occurred within 24 hours. After 1 week, neurologic examination was normal and skin lesions were disappearing (Figure 1). Qualitative analysis of the urine showed massive elevation of neutral amino acids. Sequence analysis of the SLC6A19 gene showed homozygous c.517G>A (p.Asp173Asn) mutations, the most common variant causing Hartnup disease (1). She made a full recovery.

Discussion

Niacin deficiency results in a condition known as pellagra, including the triad of photosensitive dermatitis, decline in cognition, and diarrhea, which can result in death. Niacin is consumed in the diet, but mostly synthetized by the body from the amino acid tryptophan. Deficiencies may be caused by a tryptophan-deficient diet, malabsorption (e.g., chronic diarrhea, malignancy) or a combination of both. In addition, several drugs (e.g., isoniazide, 6-mercaptopurine, 5-fluorouracil, and chloramphenicol) as well as the carcinoid syndrome may interfere with the conversion of tryptophan into niacin. Neurologic manifestations of niacin deficiency can be diverse and include cerebellar ataxia, diplopia, cognitive impairment, and psychiatric symptoms (Table 1). In an autopsy study of 230 patients with suspected Creutzfeldt-Jakob disease, 5 patients (2%) had neuropathologic features of pellagra encephalopathy, which were previously unrecognized (2).

Table 1. Neurologic Manifestations of Hartnup Disease

Neurologic Symptoms	Patients Presenting With Neurologic Symptoms, % (n/N)
Cerebellar ataxia	76 (13/17)
Hyperreflexia	47 (8/17)
Mood disturbances	41 (7/17)
Seizures	29 (5/17)
Diplopia	24 (4/17)
Hallucinations	12 (2/17)
Myoclonic twitching	6 (1/17)
Bruxism	6 (1/17)
Peripheral nerve damage	6 (1/17)

Data are from references 3–15.

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In absence of more common causes of niacin deficiency, Hartnup disease should be considered. This autosomal-recessive disorder is caused by variants in the SLC6A19 gene, encoding the B0AT1 protein that is responsible for uptake of neutral amino acids from the small intestine and reabsorption in the proximal kidney tubules (3, 4). Tryptophan is the most critical resulting deficiency because it is the precursor for niacin. Symptoms in Hartnup disease can be intermittently present and many individuals with confirmed disease will never develop symptoms (5). Precipitating factors for symptomatic disease can be fever, the use of specific medication, and/or emotional or physical stress. The reason for the onset of symptoms in our patient remains unclear.

It has been theorized that the formation of indolic compounds from undigested tryptophan could contribute to the neurologic manifestations (1). However, in our patient, symptoms improved directly after supplementation without dietary restrictions, illustrating that niacin deficiency is the most important factor in the development of symptoms in Hartnup disease. Our case illustrates the importance of recognizing the pellagra rash. Metabolic screening of plasma and urine in patients with unexplained progressive neurologic disease can provide pivotal diagnostic clues for treatable inborn error of metabolism. Early recognition and treatment of niacin deficiency is imperative and may save a life.

(7). Congenital Spinal Meningocele

Tariq Parker etal, Published December 28, 2024, N Engl J Med 2025;392: e1,DOI: 10.1056/NEJMicm2410556,VOL. 392 NO. 1

Abstract

A newborn boy was admitted to the neonatal intensive care unit for management of an open neural-tube defect. On examination, a large, red, fluid-filled sac was seen protruding through a lumbosacral defect.

(8). Westermark’s Sign and Palla’s Sign in Pulmonary Embolism

Yuichiro Shimoyama etal, Published January 1, 2025,N Engl J Med 2025;392: e2,VOL. 392 NO. 1

Abstract

A 90-year-old man with atrial fibrillation presented with sudden-onset dyspnea. Chest radiography revealed a paucity of pulmonary vasculature in the right lung fields and an enlarged right descending pulmonary artery.

Note: Westermark’s sign and Palla’s sign are radiographic findings that can help diagnose pulmonary embolism:

Westermark’s sign

A focal area of decreased blood flow in the lungs, caused by a narrowing of the pulmonary arteries.

Palla’s sign

An enlargement of the right descending pulmonary artery, which can appear as a “sausage” shape on a chest radiograph. The combination of Westermark’s and Palla’s signs is rare but can help confirm a pulmonary embolism diagnosis.

Westermark’s sign has a high positive predictive value and specificity for pulmonary embolism. However, most chest radiographs in the setting of pulmonary embolism are normal.

Swedish radiologist Nils Johan Hugo Westermark first described Westermark’s sign in 1938.

Italian radiologist Antonio Palla published his observations on Palla’s sign in 1983

(9). Chronic Myeloid Leukemia with Hyperleukocytosis

Bashir A. Bashir,Published January 1, 2025,N Engl J Med 2025;392:72,VOL. 392 NO. 1

Abstract

A 64-year-old woman presented with a 5-month history of fatigue and a 2-week history of fever and cough, with lymphadenopathy and splenomegaly. A serum sample showed a broad, greenish buffy coat of cells.

(10). Coronary Subclavian Steal Syndrome

Abstract

A 63-year-old man with a history of CABG presented with a 2-month history of angina during exertion of the left arm. Angiography revealed retrograde flow in the left internal thoracic artery graft.

Journal scan: A review of images in clinical medicine of immediate clinical significance, harvested from major international journals

Journal scan: A review of images in clinical medicine of immediate clinical significance, harvested from major international journals

From the desk of the Editor-in-chief

Journals