Ca Lâm Sàng 5

Breast ultrasound can be useful if a mass is detected to determine the nature of the mass. It is generally used following the detection of an abnormality via mammogram.

Major takeaway
Peutz-Jeghers syndrome is an autosomal dominant mutation in STK11 that is associated with speckled brown macules on the lips and around the mouth, gastrointestinal polyps and increased risks for colon, ovarian, pancreatic, and breast cancer.
Main explanation
This patient has Peutz-Jeghers syndrome (PJS), a rare inherited disease characterized by gastrointestinal polyps in association with pigmentation affecting the skin and mucous membranes.The gastrointestinal polyps are hamartomas which can show benign or malignant changes. The risk of developing some form of internal cancer is 15 times greater for patients with PJS compared with the general population – include breast, pancreatic, and colon cancer. Peutz-Jeghers syndrome is due to mutations in a serine-threonine kinase tumor-suppressor gene (STK11). It is an autosomal dominant condition.The most noticeable cutaneous feature of PJS is the appearance of pigmented macules around the mouth, lips, and gums. Therefore, his patient should have the following workup: a complete blood count to check for anemia secondary to bleeding polyps and exploratory endoscopy to determine the presence of polyps and to biopsy the polyps if present.

Laser therapy involves the use of high-intensity light to induce changes in the skin. It is useful for alleviating certain conditions. This includes telangiectasias, varicose veins, and acne scarring.

Reassurance in this context will not help the patient’s current situation. Given the bothersome nature of the polyps and the positive family history for neoplasms, it is important to use further diagnostic testing.

Topical corticosteroids are used in a number of dermatological conditions including eczema and allergic reactions. They help in decreasing local inflammation. Side-effects can include localized thinning of the skin.

Niemann-Pick disease is a rare lysosomal storage disease in which there is a deficiency in sphingomyelinase. This results in an accumulation of sphingomyelin in lysosomes. Symptoms include hepatosplenomegaly, thrombocytopenia, and ataxia.

Kartagener syndrome is a result of a defect in the dynein protein. These patients have immotile cilia. Symptoms include infertility, recurrent sinusitis, bronchiectasis, and situs inversus.

Major takeaway
Classical Ehlers-Danlos syndrome is characterized by hypermobile joints, hyperextensible skin, and easy bruising as a result of a defective collagen type V.
Main explanation
Ehlers-Danlos syndrome is an inherited disease of defective collagen synthesis. Depending on the sub-type of Ehlers-Danlos syndrome, the disease can either be autosomal dominant or recessive. Ehlers-Danlos can be sub-divided into several different types including classic (collagen type V), hypermobility, vascular (collagen type III), kyphoscoliosis, arthrochalasia, and dermatosparaxis Ehlers-Danlos syndrome. This infant in the clinical vignette is exhibiting a classical form of Ehlers-Danlos syndrome. The classical form is an autosomal dominant disorder characterized by a mutation in collagen type V. Symptoms include joint hypermobility, frequent joint dislocations, thoracolumbar scoliosis, hyperextensible skin, easy bruising, and atrophic scars. Cardiac and pulmonary conditions, while rare, can occur and include mitral valve prolapse and spontaneous pneumothorax. Physical examination shows cigarrette-paper like scars (from poor wound healing), hyperextensible skin (stretchingof skin greater than 4 centimeters), and hypermobile joints (dorsiflexion of the thumb greater than 90 degrees).

Fibrillin is a glycoprotein which provides structural support for elastin. Marfan syndrome is a disorder in which there is a defect in the fibrillin gene. These patients are tall and slender with flexible joints. They are at risk for aortic aneurysms and subluxation of the lens.

Glycogen storage disease type V, also known as McArdle disease, is a disease characterized by a deficiency in the myophosphorylase protein. Symptoms include exercise intolerance, muscle pains, and myoglobinuria.

Main explanation
Crown rump length (CRL) is the most accurate estimation of gestational age in pregnancy. It is done during the first trimester. There is little biological variability during the first trimester, so dating is thought to be accurate within 5-7 days. Dating methods during the 2nd trimester are accurate within 2 weeks, and during the 3rd they are accurate within 3 weeks.
This sonographer is measuring the length of the fetus from the top of its head to bottom of its torso – the largest dimension, excluding the yolk sac and extremities. The sac is the ring seen below the fetus. Another method to date gestational age this early is mean sac diameter(MSD), which should be larger than CRL. An MSD less than 5 mm greater than crown-rump length is a sign of risk of first trimester miscarriage.

Image Retrieved from Radiopaedia, See References

Major Takeaway: The most accurate determination of gestational age is crown-rump length during the first trimester.

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Major takeaway
Autoimmune hepatitis is an immune mediated injury of the liver cells. It is caused by aberrant HLA class II. It may present as acute hepatitis, chronic hepatitis, or cirrhosis. Anti-smooth muscle antibody (SMA) is very specific for autoimmune hepatitis.
Main explanation
Autoimmune hepatitis is an immune mediated hepatic injury. It is due to aberrant human leukocyte antigen (HLA) class II on liver cells. The aberrant HLA II induces the immune system to attack the liver causing autoimmune hepatitis. The cause of aberrant HLA is still unknown.

Autoimmune hepatitis usually occurs in women between the ages of 15 and 40. It may present as acute hepatitis, chronic hepatitis, or cirrhosis. Around one third of the patients present with symptoms of acute hepatitis which is characterized by fever, fatigue, jaundice, and upper abdominal quadrant pain. Patients with autoimmune hepatitis usually have other autoimmune diseases like Hashimoto’s thyroiditis in this patient.

Laboratory studies in autoimmune hepatitis show elevated liver enzymes (ALT and AST) and positive anti-smooth muscle antibody (SMA), antinuclear antibody (ANA), liver/kidney microsomal antibodies (LKM), and antibodies to soluble liver antigen (anti-SLA). Anti-smooth muscle antibody is most specific test for autoimmune hepatitis.

Chronic hepatitis B patients may be asymptomatic. During replicative state, patients may have fatigue, anorexia, nausea, or upper abdominal pain. Laboratory studies show low albumin, prolonged prothrombin time, high ALT, AST, and bilirubin. In chronic hepatitis B, HBsAg and anti-HBc are positive while anti-HBs are negative.

Primary biliary cholangitis (primary biliary cirrhosis) is an autoimmune destruction of bile ducts that finally leads to biliary cirrhosis. It is characterized by fatigue, pruritus, and right upper quadrant discomfort. Liver enzymes are high, especially ALP and GGT indicating biliary stasis. Antimitochondrial antibody is very specific for this disease.

The majority of acute hepatitis B infections are asymptomatic. When symptomatic, it is characterized by anorexia, nausea, vomiting, fever, jaundice, and right upper abdominal quadrant pain. Abnormal laboratory results include high liver enzymes, positive HBsAg, anti-HBc IgM antibody, and Hepatitis B-e antigen (anti-HBe). Positive anti-HBs only indicates previous immunization.

The majority of acute hepatitis C infections are asymptomatic. When symptomatic, it has the same symptoms like that mentioned in acute hepatitis B. Laboratory abnormalities in acute hepatitis C include high liver enzymes, positive HCV-RNA, and anti-HCV antibody which takes several months to be positive after the primary infection.

Atypical ductal hyperplasia is characterized by proliferation of uniform epithelial cells surrounding a portion of the duct. It shares similarities with ductal carcinoma in situ (DCIS) and is associated with an increased risk of malignancy.

Major takeaway
Fibroadenomas are common benign tumors of young women characterized by well-circumscribed, small mobile lesions within the breast that may enlarge in response to increasedestrogen.

Main explanation
Fibroadenomas are benign breast tumors that do not increase a woman’s risk for breast cancer. They are well-circumscribed, small, mobile lesions within the breast that can become larger and more tender in response to estrogen stimulation. They have been found to grow during pregnancy and menstrual cycle changes, as well as during hormonal therapy. They can regress after menopause. Ultrasound ususally shows a well-defined, solid mass. Fibroadenomas can be followed clinically by a repeat ultrasound within three to six months. Core needle biopsy or excision may be performed to confirm the diagnosis. Histologic features are remarkable for a loose, fibroblastic stroma containing ductlike, glandular spaces. These glands are located within fibrous tissues and exhibit a well-defined, intact basement membrane.

Inflammatory carcinoma is associated with lymphadenopathy as well as peau d’ orange changes of the overlying skin. It most commonly arises in women after menopause. Biopsy would show invasion of malignant cells into layers of the dermis.

Intraductal papilloma is a benign lesion of the breast. This lesion impacts the ducts of the breast, causing either serous or bloody discharge from the nipple. Intraductal papillomas can be associated with ductal carcinoma in situ (DCIS). Biopsy would show a prominent, branching fibrovascular core with myoepithelial cells

Phyllodes tumor is a rare benign breast lesion that may have malignant potential. These are large multinodular tumors, and the overlying skin may appear stretched. Like fibroadenoma, fibrotic changes are noted on biopsy; however, the biopsy of phyllodes tumor is remarkable for increased cellularity and areas of mitosis.

This ascending bacterial infection, also known as chorioamnionitis, is associated with opiate dependence during pregnancy. It is also associated with prolonged labour, and the risk of this complication increases with the number of vaginal examinations performed in the final month of pregnancy.

Major takeaway
Risk of placental abruption is increased by maternal cocaine use during pregnancy. Other poorneonatal outcomes are associated with this exposure including low birth weight, preterm delivery and intra-uterine growth restriction.

Main explanation
Cocaine use during pregnancy results in a greater risk of miscarriage and placental abruption. Cocaine is believed to reduce uterine blood flow due through vasospasm of the uterine arteries, resulting in reduced oxygen delivery to the fetus, and can lead to placental separation. Placental abruption presents with vaginal bleeding, abdominal pain and contractions. Other risk factors for placental abruption include chronic hypertension, pre-eclampsia, smoking, trauma, opiate or amphetamine use in pregnancy, and prior placental abruption.

Cocaine exposure is also associated with poor neonatal outcomes. These include low birth weight, pre-term delivery, and intra-uterine growth restriction. Cocaine exposure may also lead to neurobehavioral abnormalities between the first 48-72 hours of life, such as tremors, high-pitched cry, irritability, hyperalertness, and episodes of apnea or tachypnea. These are believed to be due to the direct effects of cocaine rather than its withdrawal.

There is no known association between autism and cocaine use during pregnancy. Autism is more common in males, and those with a family history. It is also associated with specific chromosomal abnormalities, notably Down syndrome and neurofibromatosis type 1.

Neonatal abstinence syndrome (NAS) is characterized by signs of withdrawal in a newborn exposed to particular drugs during pregnancy. NAS is most often associated with opioid exposure. Other drugs such as nicotine, benzodiazepines, and alcohol may worsen NAS. Signs include high-pitched cry, irritability, hypertonicity, feeding difficulties, and failure to thrive.

Cocaine has not been demonstrated to be a teratogen. The base rate of congenital malformations is at least 2-5%. Common drugs associated with congenital malformations include alcohol, phenytoin and lithium.

Major takeaway
HLA-B27 gene on chromosome 6 is associated with reactive arthritis, which is an autoimmune condition that develops in response to an infection in another part of the body. When reactive arthritis is related with nongonococcal urethritis, asymmetric oligoarthritis, and conjunctivitis, you called it Reiter arthritis.

Main explanation
Reactive arthritis is an autoimmune condition that develops in response to an infection in another part of the body. Coming into contact with bacteria and developing an infection triggers the disease. Reiter arthritis is characterized by nongonococcal urethritis, asymmetric oligoarthritis, and conjunctivitis. Symptoms appear within 1–3 weeks but can range from 4 to 35 days from the onset of the inciting episode of the disease. Reactive arthritis is associated with the HLA-B27 gene on chromosome 6 and by the presence of enthesitis as the basic pathologic lesion, and is triggered by a preceding infection. The most common triggering infection in the United States is a genital infection with Chlamydia trachomatis. Shigella is the most common organism causing reactive arthritis following diarrhea and Chlamydia trachomatis is the most common cause following urethritis. The diagnosis is clinical, based on the history and physical examination. No laboratory study or imaging finding is diagnostic. Treatment aims at relieving symptoms and is based on symptom severity. Two thirds of patients have a self-limited course and a 30% develop chronic symptoms.

HLA-B8 (B8) is an HLA-B serotype and is associated with Graves disease and celiac sprue. HLA-B8, previously known as HL-A8, is one of the first identified of the HLA antigens. Genes between B8 and DR3 on this haplotype are frequently associated with autoimmune disease.

HLA DR2 serotypes are associated with Goodpasture syndrome, systemic lupus erythematosus, multiple sclerosis, narcolepsy, tuberculoid leprosy, ulcerative colitis, primary biliary cirrhosis, and autoimmune hepatitis. DR2 is also found in all patients that test positive for anti-anti-Asn-RNA-synthetase and chronic interstitial lung disease.

HLA-DR3 is composed of the HLA-DR17 and HLA-DR18 split antigens serotypes. DR3 is a component gene-allele of the AH8.1 haplotype in Northern and Western Europeans. Genes between B8 and DR3 on this haplotype are frequently associated with autoimmune disease. Type 1 diabetes mellitus is strongly associated with HLA-DR3 or HLA-DR4.

HLA-DR5 is associated with persistent generalized lymphadenopathy and Kaposi sarcoma in AIDS, juvenile rheumatoid arthritis, pernicious anemia, Hashimoto thyroiditis, mycosis fungoides, polyglandular deficiency syndrome, systemic sclerosis, childhood epilepsy, early-onset alopecia areata, short-ragweed Ra6 allergy, primary antiphospholipid syndrome, and increased longevity in the Dutch.

Attention and calculation are tested through serial 7 subtraction, in which patients are instructed to begin at a number (typically 100) and count down by 7s.
In older versions of the mini-mental state examination, an alternate task is spelling “world” backwards.

Naming – Pointing to a body part and having subject name it
Repetition – Say a sentence and have subject repeat
Reading – Have subject read and obey a command (“close your eyes”)
Writing – Have subject write any sentence
Drawing – Instruct subject to draw two intersecting pentagons (with reference image)

The mini-mental state examination tests orientation to time (year, season, month, day of the week, date) and place (state, city, county, building, floor)

Major takeaway
The Folstein Mini-Mental State Examination measures various functions of cognition. Registration is tested by naming 3 objects and having the patient repeat them, while recall involves the patient repeating the same 3 objects after being briefly distracted.
Main explanation
The Mini-Mental State Examination (MMSE; Folstein test) is a 30-point test that measures cognitive impairment in cases of non-focal neurological deficit (confusion, delusion, dementia, memory loss, schizophrenia, etc.). It typically tests (sample pneumonic: ORACLe):

1. Orientation (time and place)
2. Registration and recall
3. Attention and calculation
4. Comprehension (following commands)
5. Language (naming, repetition, reading, writing, and drawing)
Recall is tested by having the subject repeat 3 pre-registered words after a period of distraction (doing other tasks in the mini-mental-state examination).

Revised in 2010, the MMSE-2 was introduced in 3 versions. The standard version tests the same core cognitive skills, with alterations to some tasks.

Intended to further differentiate less-severe cases of cognitive impairment (mild cognitive impairment, subcortical dementia), the extended version of the MMSE-2 has a 90-point scale and tests the same tasks with the addition of

1. Story memory – Immediate recall of a brief story
2. Processing speed – Symbol-digit coding
The brief, 16-point version only tests orientation, registration, and recall, making it useful as a quick, non-specific screen for cognitive impairment

Administrators of the mini-mental state examination evaluate registration by naming 3 unrelated words and having the subject promptly repeat those words without any intervention between hearing and speaking the words.

Caudal regression syndrome is a disorder characterized by hypoplasia of the sacrum. Maternal diabetes mellitus is a major risk factor for this condition. Depending on the severity, some children may require the use of prosthetics.

Gastroschisis is an abdominal wall defect in which the internal abdominal organs such as the intestines herniate outside without a protective sac. Screening for gastroschisis is done by measuring alpha-fetoprotein. Treatment is surgery.

Rubella, and other “TORCH” infections can cause cardiac malformations in the newborn. Rubella is associated with a patent ductus arteriosus.

Macrosomia, or large for gestational age, is a term used to describe newborns who are greater than 90th percentile for weight at birth.

Major takeaway
Fetal exposure to parvovirus B19 in pregnant women is associated with spontaneous abortion, hydrops fetalis, and stillbirth. The risk is highest before 20 weeks.
Main explanation
Parvovirus B19 is a single stranded and naked DNA virus which can be spread through respiratory droplets. Parvovirus B19 can cause erythema infectiosum (also known as the “slapped cheek syndrome”) in children. These patients will have a “slapped cheek” rash followed by a lacey rash which develops along the trunk. In adults, the virus causes nonspecific symptoms such as fatigue and arthralgias. However, parvovirus B19 can also be transmitted vertically from the mother to the fetus during pregnancy. Fetal infection of the virus, especially before 20 weeks gestation, has been associated with spontaneous abortion, hydrops fetalis, and stillbirth.

Fructose and sucrose should be avoided in patients with hereditary fructose intolerance. The key identifying feature of HFI is the appearance of symptoms with the introduction of fructose to the diet. Affected individuals are asymptomatic and healthy, provided they do not ingest foods containing fructose or any of its common precursors, sucrose and sorbitol.

Fructose is a monomer – it does not contain galactose. The key identifying feature of HFI is the appearance of symptoms with the introduction of fructose to the diet. Affected individuals are asymptomatic and healthy, provided they do not ingest foods containing fructose or any of its common precursors, sucrose and sorbitol.

Major takeaway
Galactosemia is an autosomal recessive disorder due to a lack of galactose-1-phosphate uridyl transferase. Avoid breastfeeding in children with galactosemia because lactose in the milk contains galactose and glucose monosaccharides.

Main explanation
Galactosemia is a deficiency in galactose-1-phosphate uridyltransferase, an enzyme that converts galactose-1-phosphate to glucose-1-phosphate. Symptoms include failure to thrive, jaundice, hepatomegaly, infantile cataracts and intellectual disability. Patients should exclude galactose and lactose (galactose + glucose) from diet.

Infants are routinely screened for galactosemia in the United States, and the diagnosis is made while the person is still an infant. Infants affected by galactosemia typically have symptoms of lethargy, vomiting, diarrhea, failure to thrive, and jaundice. None of these symptoms are specific to galactosemia, often leading to diagnostic delays. Luckily, most infants are diagnosed on newborn screening. If the family of the baby has a history of galactosemia, doctors can test prior to birth by taking a sample of fluid from around the fetus (amniocentesis) or from the placenta (chorionic villus sampling or CVS).

Lactose should also be avoided in patients with galactosemia. This is because lactose is a disaccharide containing glucose and galactose monomers bound together

Glucose is a monomer – it does not contain galactose. In diabetes mellitus, patients become hyperglycaemic due to insulininsensitivity.