The US FDA has approved the gene therapy betibeglogene autotemcel (Zynteglo) for adult and pediatric patients with beta-thalassemia who require regular red blood cell transfusions. Functional copies of the mutated gene are inserted into patient’s hematopoietic stem cells via a replication-defective lentivirus. A one-time gene therapy cost $2.8 million. Adverse events such as abdominal pain, hot flush, dyspnea, tachycardia, noncardiac chest pain, and cytopenias were noted.
A novel zoonotic RNA Langya virus (LayV) is a henipavirus first detected in the China provinces of Shandong and Henan. The name of the virus refers to Mt. Langya.
Symptoms: fever, fatigue, cough
Langya henipavirus affects humans, dogs, goats, and its presumed original host are shrews.
Lab findings in patients: thrombocytopenia, leukopenia, impaired liver and kidney function test.
Treatment: No specific drug or vaccination only supportive care.
Monkeypox is a zoonotic orthopoxvirus.
Usual onset: 5–21 days post-exposure.
Duration: 2 to 4 weeks.
Route: Human-to-human transmission, exposure to infected body fluids or contaminated objects by small droplets through the airborne route.
Symptoms: Fever, headache, muscle pains, shivering, mostly nonitchy blistering rash on face, hands, soles and swollen lymph nodes.
Complications: Secondary infections, eye infection, visual loss, scarring, encephalitis, sepsis, bronchopneumonia.
Types: Central African (Congo Basin), West African
Diagnosis: Testing for viral DNA PCR
Differential diagnosis: Chickenpox, smallpox
Prevention: Smallpox vaccine, hand washing, covering rash, PPE
Treatment: Supportive, antivirals, vaccinia immune globulin
Medication: Tecovirimat
History: A 50-year-old woman presented with asymptomatic multiple cutaneous nodules all over the body of 4 months duration. Cutaneous examination showed multiple hyperpigmented nodules and plaques involving face, trunk, and extremities. Peripheral smear showed abnormally elevated leucocyte count (TLC-70,000) with abnormal cells: myeloblasts 40%, promyelocytes 8% and myelocytes 39%. Auer rods were present in few myeloblasts. What is the most likely diagnosis?
Answer:
Leukemia cutis is the infiltration of neoplastic leukocytes or their precursors into the epidermis, the dermis, or the subcutis, resulting in clinically identifiable cutaneous lesions. Leukemia cutis may follow, precede or occur concomitantly with the diagnosis of systemic leukemia.
The clinical appearance of leukemia cutis is variable with erythematous to violaceous papules or nodules being the most frequent lesions (60%), followed by infiltrated plaques, generalised cutaneous eruption and erythroderma. They are frequently asymptomatic. The nodules are typically firm or rubbery in consistency, and can become purpuric if the patient is thrombocytopenic.
The US FDA approves crizotinib (Xalkori) for the treatment of unresectable, recurrent, or refractory inflammatory anaplastic lymphoma kinase (ALK)-positive myofibroblastic tumors (IMT) in adults and children over 1 year of age.
Crizotinib is a selective tyrosine kinase inhibitor currently approved for the treatment of metastatic non-small cell lung cancer in patients whose tumors are positive for ALK or ROS1 as detected by an FDA-approved test, and for ALD-positive anaplastic large cell lymphoma.
Adverse reactions occurring in 35% or more pediatric patients included vomiting, nausea, diarrhea, abdominal pain, rash, vision disorder, upper respiratory tract infection, cough, pyrexia, musculoskeletal pain, fatigue, edema, constipation, and headache.
History: A 30 yr old obese man presents with an asymptomatic rash on his back, arms, and hands that had developed 2 week earlier. On physical examination, scattered pink-yellow papules were present on the upper back, extensor surfaces of the upper arms, and dorsa of the hands. A fasting blood sample was grossly lipemic. Which of the following is the most likely diagnosis?
Answer: Eruptive xanthomas typically present as crops of 2–5 mm yellow papules with a red rim over extensor surfaces such as the buttocks or shoulders, but can be widespread including inside the mouth. The papules may be tender and are usually itchy. They may demonstrate köbnerisation. Eruptive xanthomas are due to hypertriglyceridaemia (triglyceride >11.2 mmol/L) of any cause.
The US FDA has approved dabrafenib + trametinib for adult and pediatric patients aged 6 years and older with unresectable or metastatic solid tumors with the BRAF V600E mutation whose disease has progressed following prior treatment and who have no satisfactory alternative treatment options.
The combination represents “the first and only BRAF/MEK inhibitor to be approved with a tumor-agnostic indication for solid tumors carrying the BRAF V600E mutation, which drives tumor growth in more than 20 different tumor types, and it is the only BRAF/MEK inhibitor approved for use in pediatric patients.
The combination already carries indications for BRAF-mutated melanoma, non–small cell lung cancer, and thyroid cancer. The new approval was based on two adult trials and one pediatric trial that showed an overall response benefit for patients with high- and low-grade gliomas, biliary tract cancers, and certain gynecologic and gastrointestinal cancers.
The US FDA has approved Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for BBS, a rare genetic disorder that impairs a hunger signal along the melanocortin-4 receptor (MC4R) pathway.
Individuals with Bardet-Biedl Syndrome typically have obesity that starts at age 1 along with insatiable hunger (hyperphagia). Available weight management options are generally unsuccessful. Other symptoms may include retinal degeneration, reduced kidney function, or extra digits of the hands or feet.
The most common adverse reactions (with an incidence ≥ 20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.
Patients with locally advanced rectal cancer and tumors with deficient mismatch repair (dMMR) have shown a remarkable response to treatment with the programmed cell death-1 (PD-1) inhibitor dostarlimab (Jemperli).
So far, the study has involved only 12 patients, but all of them have had a clinical complete response to treatment. They continue to show no signs of cancer (during follow-up ranging from 6 to 25 months) and have not undergone surgery or had radiation and chemotherapy, which are the standard treatment approaches.
Dostarlimab is already approved by the US Food and Drug Administration for use in the treatment of recurrent or advanced endometrial cancer with dMMR. Rectal cancer is an off-label use.
All patients had mismatch repair-deficient stage 2 or 3 rectal adenocarcinoma. The authors note that these tumors respond poorly to standard chemotherapy regimens, including neoadjuvant chemotherapy. The median age of enrolled patients was 54 years and 62% were women.
Source: NEJM
History: A 50-year-old woman with painless swelling in her left foot. The swelling started after a banal penetrating injury on the sole of her left foot 23 years ago. X-rays images showed multiple osteolytic lesions of the tarsus.
a) Eumycetoma
b) Sporotrichosis
c) Chromoblastomycosis
d) Histoplasmosis
e) Lobomycosis
Answer:
Eumycetoma, also known as Madura foot.
Causes Madurella spp., Leptosphaeria senegalensis, Curvularia lunata, Pseudallescheria spp., Neotestudina rosatii, Acremonium spp. and Fusarium spp.
Symptoms: Swelling, weeping pus filled sinuses, deformity.
Diagnostic method Microscopy, biopsy, culture, medical imaging, ELISA, immunodiffusion, DNA sequencing
Differential diagnosis: Actinomycosis (Actinomycetoma)
Treatment Surgical debridement, antifungal medicines
Medication Itraconazole, posaconazole, voriconazole
Complications: Amputation
Prognosis Recurrence is common
Frequency Endemic in Africa, India and South America
