Ca Lâm Sàng 8

Bleomycin induces the formation of free radicals, which causes breaks in DNA strands. It is known to cause pulmonary fibrosis, skin changes, and occasionally bone marrow suppression.

Busulfan is a DNA alkylator used in chronic myelogenous leukaemia (CML), other leukemias, lymphomas, and myeloproliferative disorders. It is known to cause pulmonary fibrosis and skin changes, including hyperpigmentation.

Major takeaway
Cisplatin, an alkylating-like agent, crosslinks DNA thereby interfering with mitosis. It is used in the treatment of germ cell tumors such as testicular cancer and has many side effects, including ototoxicity.

Main explanation
This question is testing your knowledge of the major toxicities of chemotherapeutic agents. Cisplatin, an alkylating-like agent, crosslinks DNA thereby interfering with mitosis.

Cisplatin has a four main side effects:
1. Nephrotoxicity (kidney damage) is a major concern. The dose is reduced when the patient’s creatinine clearance (a measure of renal function) is reduced. Adequate hydration and diuresis is used to prevent renal damage. The nephrotoxicity of platinum-class drugs seems to be related to reactive oxygen species and in animal models can be ameliorated by free radical scavenging agents
2. Ototoxicity (hearing loss): there is at present no effective treatment to prevent this side effect, which may be severe. Audiometric analysis may be necessary to assess the severity of ototoxicity. Other drugs (such as the aminoglycoside antibiotic class) may also cause ototoxicity, and the administration of this class of antibiotics in patients receiving cisplatinis generally avoided.
3. Nausea and vomiting: cisplatin is one of the most emetogenic chemotherapy agents, but this symptom is managed with prophylactic antiemetics (ondansetron, granisetron, etc.) in combination with corticosteroids.
4. Neurotoxicity (nerve damage) can be anticipated by performing nerve conduction studiesbefore and after treatment. Common neurological side effects of cisplatin include visual perception and hearing disorder, which can occur soon after treatment begins.

Cytarabine is used mainly in the treatment of cancers of white blood cells such as acute myeloid leukemia (AML) and non-Hodgkin lymphoma. It inhibits DNA polymerase and causes megaloblastic anemia and pancytopenia.

Doxorubicin generates free radicals and intercalates in DNA, creating breaks in the DNA. It is used to treat leukemias and Hodgkin’s lymphoma, as well as cancers of the bladder, breast, stomach, lung, and ovaries. It causes cardiotoxicity, hair loss, and bone marrow suppression.

Acute lymphoblastic leukemia (ALL) is characterized by increased lymphoblasts. ALL is a disease which generally affects the pediatric population and has been associated with Down syndrome. Symptoms include lethargy, anemia, weight loss, and petechiae. Because of advancements in medicine, 5-year survival rates remain excellent.

Hepatoblastoma is a pediatric malignancy of the liver. α-fetoprotein concentrations will be elevated and the mass can be palpatedon physical examination. Hepatoblastoma has also been associated with familial adenomatous polyposis. Treatment generally involves surgical resection with chemotherapy and liver transplant.

Major takeaway
Neuroblastoma is the most common malignant tumor of infancy and early childhood. The cancer is invasive and is often characterized by metastatic to the bone marrow, liver, lymph nodes, skin, and orbits.
Main explanation
Neuroblastoma is a common malignant tumor of neural crest cells. It is the most common malignancy of infancy and early childhood. Neuroblastoma is a very invasive malignancy with metastasis to the bone marrow, liver, lymph nodes, skin, and orbits at the time of diagnosis. Most neuroblastomas begin in the abdomen in the adrenal gland, next to the spinal cord, or in the chest. Symptoms of neuroblastoma can include abdominal distension, pale skin, periorbital ecchymosis, chronic cough, and bone pain. Central nervous system involvement may produce symptoms such as urinary retention, and paralysis of the lower extremities. Also present could be uncontrolled eye, leg, or feet movements. This constellation of symptoms is known as the opsoclonus-myoclonus syndrome or “dancing eyes and dancing feet” syndrome.

Histopathology includes small round blue cells and Homer Wright rosettes. Urine studies show elevated concentrations of homovanillic and vanillylmandelic acid. A computed tomographyscan can be done to evaluate size and extent of the tumor for surgical resection. Neuroblastoma can be hereditary as it has been found to be associated with the N-myc oncogene.

Renal cell carcinoma is extremely rare malignancy in childhood and tends to be characterized by the classic triad of hematuria, flank pain, and an enlarging abdominal mass. Systemic signs of illness include night sweats, fevers, chills, and weight loss.

Wilms tumor is the second most common renal malignancy in the pediatric population. Ultrasound and computed tomographyshow a mass arising from renal tissue. Histopathologic section shows a triphasic tumor arising from the fetal kidney with blastemal, stromal, and epithelial components. Unlike neuroblastoma, Wilm tumor is a smooth tumor which does not cross the midline.

Stroke is characterized by an acute onset of focal neurologic deficit (such as drooping of the face, slurring of speech, muscle weakness, etc). Stroke can be either hemorrhagic or embolic in nature. Risk factor for stroke include diabetes mellitus, atrial fibrillation, and hypertension.

Lyme disease is caused by a spirochete known as Borrelia burgdorferi and is transmitted by the Ixodes scapularis tick (commonly known as the deer tick). The severity of Lyme disease can vary and symptoms include a bulls-eye rash, heart block, Bell palsy, migratory arthritis, and encephalopathy.

Major takeaway
Fibrinoid leukodystrophy (also known as Alexander disease) predominantly affects children and is characterized by white matter changes with abnormalities of the basal ganglia, thalamus, and brain stem.
Main explanation
Fibrinoid leukodystrophy (also known as Alexander disaese) is an autosomal dominant genetic disorder characterized by a mutation in the glial fibrillary acidic proteins on chromosome 17. While this condition is very rare, it predominantly affects infants and children. There exists 4 subtypes of this disease: neonatal, infantile, juvenile, and adult. Diagnosis is based upon magnetic resonance imaging studies. Criteria for diagnosis are as follows:

1) extensive cerebral white matter changes that show frontal predominance
2) Periventricular rim (with high signal on T1 and low signal on T2)
3) Abnormality of basal gangila and thalami
4) Brain stem abnormality
5) Enhancement of contrast of grey and white matter structures

Pathologic examination of the brain tissue will show the presence of Rosenthal fibers. Symptoms include seizures, spasticity, and cognitive dysfunction. The condition does not have a cure and is both progressive and inevitably fatal.

Huntington’s disease is a progressive autosomal dominant genetic condition characterized by trinucleotide repeats. The condition is associated with chorea and dementia.

Multiple sclerosis is an auto-immune condition characterized by the demyelination of neurons resulting in damage of the central nervous system. Diagnosis is made by white matter lesions characterized by both time and space. As with most auto-immune conditions, women are more at risk to develop multiple sclerosis than men.

Benign hereditary chorea is predominant among children age 5 years and younger. This condition is characterized by delayed motor and walking milestones.

Huntington disease is an autosomal dominant disorder characterized by degeneration of the striatum, predominantly affecting the caudate nucleus. The clinical presentation includes loss of motor control (that manifests as chorea), as well as cognitive impairmentand affective disturbance.

Lesch-Nyhan syndrome, caused by a mutation of hypoxanthine phosphoribosyltransferase, is characterized by psychomotor retardation, and hypotonia, with subsequent spasticity and choreoathetosis. Self-mutilation is a characteristic feature.

Major takeaway
Sydenham chorea is the most common cause of chorea in children. It typically manifests a few months following a group A streptococcal infection and is characterized by involuntary movements of the face and extremities.
Main explanation
Sydenham chorea is a neurological manifestation of rheumatic fever and is the most frequently acquired form of chorea in children. The disease is characterized by spontaneous and involuntary choreiform movements that affect the face and extremities. Emotional changes like crying and inappropriate laughing may precede the development of chorea.

Sydenham chorea typically begins with distal movements of the hands, but generalized jerking of the face and feet may also occur. The movements are continuous, rapid, and irregular, occurring only while the patient is awake. Sydenham chorea is usually a late manifestation of rheumatic fever, occurring 1-8 months after Streptococcus pyogenes pharyngitis. The muscle weakness presents as an inability to maintain a tetanic contraction, known clinically as the “milkmaid’s grip,” in which patients are unable to clench their fists for a long period of time. To compensate for this, they relax and tighten intermittently when asked to grip the examiner’s fingers.

The Jones Criteria is used to diagnose rheumatic fever. A good mnemonic for the Jones Criteria is SPACE: Subcutaneous nodules, pancarditis, arthritis, chorea, and erythema marginatum.

Tourette syndrome is clinically characterised by tics, like eye blinking echolalia, coprolalia, abnormal gait, kicking, and jumping. The characteristic feature of Tourette syndrome tics is the presence of premonitory feelings or sensations, which are relieved by the execution of the tic.

Cervicitis from Chlamydia trachomatis infection is characterized by vaginal discharge, abnormal vaginal bleeding, and purulentendocervical discharge. Pain may manifest with an ascending infection causing pelvic inflammatory disease.

Genital herpes simplex virus (HSV) infection is characterized by painful genital ulcers, dysuria, fever, inguinal lymphadenopathy, and headache. HSV infection may be mild or asymptomatic in some individuals.

Most Neisseria gonorrhoeae infections are asymptomatic in women. N. gonorrhoeae cervicitis can manifest with vaginal pruritus, mucopurulent cervical discharge, dysuria, or perilabial pain.

Syphilis is caused by the bacterium Treponema pallidum. Syphilis is initially characterized by a painless chancre at the site of inoculation which heals within a few weeks. Secondary syphilis may develop later and is characterized by fever, rash, headache, malaise, diffuse lymphadenopathy, and other systemic symptoms.

Major takeaway
Trichomoniasis is a protozoan infection of the urogenital tract that usually leads to vaginitis in women. It is characterized by vaginal and vulvar erythema, vaginal burning and pruritus, and foul, thin, yellow-green discharge.
Main explanation
Trichomoniasis is a genitourinary infection caused by the protozoan Trichomonas vaginalis. It is the most common sexually transmitted disease worldwide. Trichomoniasis in women usually takes the form of vaginitis, which is characterized by a purulent, malodorous, thin discharge, vaginal burning, and pruritus, dysuria, freuency, or dyspareunia. Erythema of the vulva and vaginal mucosa are often present. A “strawberry cervix”, referring to punctuate hemorrhages on the vagina and cervix, may be observed as well. T. vaginalis infection is associated with a vaginal pH >4.5 Trichomoniasis can be diagnosed on a wet mount, which would show distinct motile trophozoites. Trichomoniasis is treated with t-nitroimidazole drugs (metronidazole or tinidazole). Both the patient and the patient’s sexual partner(s) must be treated in order to prevent reinfection.

Major takeaway
Autism spectrum disorder is characterized by impaired social interaction with significant language and cognitive delays. Onset is typically in early childhood, and diagnostic criteria includes restricted repetitive range of interests, behaviors and activities.
Main explanation
The child in this vignette most likely has Autism Spectrum Disorder (ASD). ASD is characterized by impaired social interactions with significant language and cognitive delays. ASD typically manifests early in childhood and is characterized by qualitative abnormalities in social interactions and aberrant communication skills. Patients with ASD often display repetitive or restricted behaviors, similar to the patient in the vignette who was stacking-unstacking blocks. Other behaviors that suggest autism include developmental regression, absence of protodeclarative pointing, abnormal reaction to environmental stimuli, absence of smiling when greeted by familiar people, absence of typical responses to pain and injury, language delays, susceptibility to infection and febrile illness, and absence of symbolic play. The etiology of ASD is largely unknown, and was recently re-classified by the DSM-V in 2013 to include disorders that previously fell under the category of Pervasive Developmental Disorders. Diagnostic criteria for ASD includes impairment in social communication and interaction, as well as restricted repetitive range of interests, behaviors and activities. Other medical conditions and developmental disorders must be ruled out to make the diagnosis.

Cri-du-chat syndrome consists of multiple congenital anomalies as well as mental retardation, microcephaly, facial abnormalities, and a mewing cry in infants with a deletion on the short arm of chromosome 5.

Fragile X syndrome is an inherited cause of intellectual disability, usually among boys, with physical abnormalities such as an elongated face, large protruding ears, macroorchidism, and behavioral changes.

Oppositional defiant disorder is defined as a pattern of angry/irritable mood, argumentative/defiant behavior, or vindictiveness lasting at least 6 months and typically directed towards authority figures.

Rett syndrome is a genetic postnatal neurological disorder of the grey matter of the brain. Clinical features include small hands and feet, deceleration of the rate of head growth, repetitive stereotyped hand movements, susceptibility to gastrointestinal and seizure disorders, as well as growth abnormalities.

Multiple myeloma can cause bone pain and elevated ESR, but it does not occur in the distribution shown here. Monoclonal proteins in the serum or urine are diagnostic

Major takeaway
Polymyalgia rheumatica is an inflammatory rheumatologic condition in adults. Morning stiffness of the shoulders and hip girdle is the most prominent symptom. It is associated with giant cell arteritis.
Main explanation
Polymyalgia rheumatica (PMR) is an inflammatory condition that occurs almost exclusively in adults. It is the second most common systemic rheumatic disease after rheumatoid arthritis.
Patients present with symmetrical morning stiffness and/or pain in the shoulders, hip girdle, neck, and torso. Weakness is subjective, but decreased range of motion is apparent during physical examination. Patients may also experience systemic symptoms such as malaise, weight loss, and fever.
There is an important association between PMR and giant cell (temporal) arteritis. About 50% of patients with temporal arteritis have PMR, and up to 30% of patients with PMR experience symptoms of giant cell arteritis.
Diagnosis is based on symptoms and increased ESR and CRP. Normocytic anemia is another common but nonspecific finding.
Resolution usually occurs within 3 days of starting a low-dose glucocorticoid, and this response often confirms the diagnosis.

Overlapping features of rheumatoid arthritis (RA) are symmetrical polyarthritis, morning stiffness, and elevated ESR. However, it classical affects the small joints of the hands and feet.

One adverse effect of statins is myopathy, but it is not worse in the morning, nor is it symmetrically distributed. Serum creatine kinase would be elevated, and there is objective weakness.

Fibromyalgia is characterized by widespread musculoskeletal pain of long duration, rather than subacute onset. Furthermore, laboratory values are normal in fibromyalgia.

Infectious colitis is the most common cause of colitis in children. Bacterial colitis is commonly caused by E. coli, Shigella, Salmonella and Campylobacter. Entamoeba histolytica is the most common cause of parasitic colitis. Viral colitis occurs in immunocompromised patients from cytomegalovirus. Diarrhea, abdominal tenderness, fever, and positive stool samples are common findings.

Inflammatory bowel disease includes Crohn disease and ulcerative colitis. Ulcerative colitis is confined to the colon while Crohn disease can involve any portion of the gastrointestinal tract. Diarrhea occurs in inflammatory bowel disease, usually with bloody stool. Symptoms include malabsorption and extraintestinal manifestations such as uveitis, arthritis, erythema nodosum, and cholangitis.

Major takeaway
Irritable bowel syndrome is characterized by chronic abdominal pain with associated diarrhea or constipation. It is associated with anxiety and stress.

Main explanation
Irritable bowel syndrome (IBS) is characterized by abdominal pain and a change in bowelhabits at least once a week for at least three months. To make a definitive diagnosis, the Rome IV criteria require that symptoms began at least 6 months ago, but IBS is still the most likely diagnosis in this patient.
There is no identifiable cause but symptoms are thought to result from abnormal contractionsof the colon and small intestines. Women are twice as likely as men to have IBS. The abdominal pain in IBS is usually crampy and manifests with stress.

IBS can be subdivided into diarrhea-predominant, constipation-predominant, and alternating types. Diarrhea is most common in the mornings or after meals and accompanied by urgency and a feeling of incomplete emptying. Other symptoms include bloating, gas, and belching. Diagnosing IBS involves ruling out other diseases that present similarly. Most physicians will order routine blood tests as well as endoscopic studies. Physical examination is grossly normal in these patients but the patient may show signs of anxiety.

Treatment involves monitoring foods that may be causing symptoms and eliminating them from the diet. Increasing fiber helps, especially in constipation-predominant IBS. Psychosocial therapy for stress and anxiety has been helpful for some people. Medications are used to manage bowel-related symptoms. Antibiotics and probiotics can also be used

Insufficient blood supply to a portion of the colon causes ischemic colitis. There are many etiologies of ischemic colitis including embolic disease, vasculitis, aortic aneurysm, irradiation, and shock. It is mainly a disease seen in older people. Radiographicimaging is typically used in the diagnosis.

Short bowel syndrome is also a cause of diarrhea in the pediatric population. It can be caused by necrotizing enterocolitis, volvulus, and inflammatory bowel disease among others which result in bowel resection. Patients will also have malnutrition and likely anemia. History usually reveals a bowel resection or other bowel-associated pathology.

In the DSM-V, there is no specific number of pain symptoms or organ systems that must be present in order to qualify for a somatic symptom disorder.

Somatoform disorders have a high comorbidity with anxiety and depressive disorders. The presence of another mental illnesswould not exclude the possibility of a co-existing somatic disorder. A panic disorder would not fully account for this woman’s symptoms.

While somatic symptom disorders usually beginning before age 30 and are more prevalent in women, age and gender are not diagnostic criteria.

Somatic symptom disorders typically do not respond to medications. However, the presence of other medical conditions does not rule out the presence of a somatic symptom disorder.

Major takeaway
Major depressive disorder can be characterized by somatic symptoms. The presence of mood symptoms beginning before somatic symptoms would suggest that depression is the primary underlying condition.

Main explanation
Somatic symptom disorder is characterized by multiple somatic complaints that are distressing or cause significant disruption and cannot be explained by another medical condition. While the somatic symptoms are caused by psychological factors, the patient may or may not suffer from any mental or emotional symptoms.
Major depressive disorder is a distinct diagnosis that may be characterized by somatic symptoms. The presence of mood symptoms beginning before somatic symptomswould suggest that depression is the primary underlying condition. While is it possible for a patient to have two or more different mental illnesses, one should not give two different diagnoses if the patient’s symptoms are better described by one disorder.

Major takeaway
Acute epiglottitis is a potentially life-threatening airway condition characterized by respiratorydistress, stridor, copious drooling, and pharyngitis that is now uncommon due to the high uptake of the Haemophilus influenza B vaccine. The priority of management is obtaining a secure airway.
Main explanation
Main Explanation: In a child with acute onset fever, drooling, and significant respiratory distress, epiglottitis must be considered due to the risk of rapid airway compromise. Other signs to look for are a toxic appearance and muffled voice in children aged 6 to 12. This acute inflammation of the epiglottis was historically caused by Haemophilus influenza type B (Hib). Since the introduction of the Hib vaccine, the incidence of acute epiglottitis has decreased by 95% and cases more commonly arise in adults and older children due to pathogens including Streptococcus pneumoniae. Still, consider this diagnosis in children who are immunocompromised, or who may not have received the immunization, such as this adopted boy with unknown prior history. With acute epiglottitis, rapid recognition and airwaymanagement is key. From the beginning of symptoms to required hospitalization is less than 24 hours, often less than 12 hours. Lateral X-rays of the neck can be used to be confirm the diagnosis by identifying the ‘thumbprint sign’. However, the priority of management is obtaining a secure airway, usually with endotracheal intubation, and it is not safe to send a patient with suspected epiglottitis for imaging prior to doing so.

Incorrect: Although croup is the most common cause of stridor in children, it is typically seen children aged six months to three years. Additionally, a cough (typically described as barking or seal-like), is required for this diagnosis, but is absent here.

Incorrect: Bronchiolitis is characterized by nasal congestion and discharge followed by fever, wheezing, and cough and is typically seen children two years old and younger. This boy’s age, rapid fever onset, copious drooling, and inspiratory stridor make this diagnosis less likely

Incorrect: Despite the history from the mother, the presence of high fever suggests an infectious cause of respiratory distress in this child and epiglottitis must be considered due to the risk of complete obstruction and respiratory arrest.

Incorrect: Although excessive drooling and neck extension are characteristic of abscess formation in the retropharynx, this boy’s abrupt onset of respiratory distress and high fever, and lack of neck mass make an abscess in this area less likely. X-ray imaging is critical in confirming the diagnosis in this case.