CA LÂM SÀNG 10

Carcinoma of the pancreas rarely has ben associated with generalized pruritus. It has been known to be an important symptom in other malignancies.

Pruritus may be seen in cases of hyperthyroidism, but other symptoms of hyperthyroidism are absent in this patient (flushing, heatintolerance, weight loss, anxiety, etc.).

Major takeaway
Intrahepatic cholestasis of pregnancy is a reversible form of cholestasis affecting some pregnant women in their second or third trimesters characterized by hepatic dysfunction and pruritus of the skin caused by elevated bile acids in the bloodstream, causing bile saltdeposition in the skin, and secondary skin lesions due to scratching only (no primary lesions).
Main explanation
Pruritus gravidarum is also known as intrahepatic cholestasis of pregnancy. It is a reversible form of cholestasis affecting some pregnant women in their second or third trimesters. It is believed to be linked to female sex hormone changes that take place in the body during pregnancy and, in some cases, patients who are not pregnant but who are taking oral contraceptive pills.

The hallmark of this condition is pruritus of the skin caused by elevated bile acids in the bloodstream, which lead to bile salt deposition in the skin, and secondary skin lesions due to scratching only (no primary lesions). Jaundice may develop with cases of severe cholestasis. The diagnosis of pruritus gravidarum/intrahepatic cholestasis of pregnancy is confirmed by the laboratory finding of serum bile acids of greater than 11.0 μmol/L.

Pruritus and excoriations of the skin should lessen with treatment and disappear after the patient gives birth. Patients should be advised to avoid picking at their skin to avoid scarring and/or secondary infections.

Pruritus is often associated with pregnancy, most often due to changes in the skin, especially that of the abdomen. Pruritus gravidarum is not caused by uterine dysfunction.

The thymus is a primary lymphoid organ of immune tissue. It does play a roll in hypersensitivity reactions, but pruritus gravidarum is not caused by thymic dysfunction.

Distal interphalangeal joint involvement is characteristic of osteoarthritis but not rheumatoid arthritis. Unless a secondary condition, such as trauma, metabolic disorder, or inflammatory arthritis, has already affected the joint, osteoarthritis does not occur in the metacarpophalangeal, wrist, elbow, shoulder, and ankle joints.

Psoriasis is associated with an underlying inflammatory arthritis in up to 30% of patients with skin disease; nail pitting suggests psoriatic arthritis, even in the absence of psoriatic skin lesions. These changes are not present in this patient.

Major takeaway
Rheumatoid arthritis and osteoarthritis can both involve the proximal interphalangeal joints of the hands, but metacarpophalangeal joint involvement occurs in rheumatoid arthritis and not osteoarthritis.
Main explanation
This patient has symptoms and signs consistent with rheumatoid arthritis. Different joints are variably affected by different disorders. Rheumatoid arthritis and osteoarthritis can both involve the proximal interphalangeal joints of the hands, but metacarpophalangeal jointinvolvement occurs in rheumatoid arthritis but not typically in osteoarthritis. This patient has erythema and swelling of the metacarpophalangeal joints and loss of function leading to absenteeism from work; these findings are most consistent with rheumatoid arthritis. Women are more commonly affected and HLA-DR4 is associated. High rheumatoid factor (RF) is associated with severe disease, although 3% of the healthy population has RF. Synovial analysis will show findings consistent with an inflammatory process (clear/yellow fluid; >2,000/mm3 leukocytes; 50-70% PMNs).

More than 90% of patients with SLE develop joint involvement that can manifest as arthralgia or true arthritis. Joint pain is often migratory and can be oligoarticular or polyarticular and asymmetric or symmetric. The absence of other manifestations of SLE (serositis, cytopenias, kidney disease, rash, photosensitivity) make this diagnosis unlikely.

A small percentage of gout patients present with polyarticular gout, mimicking RA. Tophi and high levels of uric acid are specific for gout and very rare in RA. In addition, erosions seen in gout where the tophi have eroded into the bone are different from the erosions in RA.

Major takeaway
One of the most common causes of abnormal uterine bleeding is anovulation due to an immature hypothalamic-pituitary-gonadal axis leading to dysfunctional uterine bleeding. The administration of oral contraceptive pills is a common treatment.

Main explanation
This teenage patient presents with heavy menstrual periods of irregular duration consistent with a diagnosis of abnormal uterine bleeding (AUB). A very common cause of AUB in this population is anovulation due to an immature hypothalamic-pituitary-gonadal axis leading to dysfunctional uterine bleeding. The diagnosis requires ruling out any underlying pathological and anatomical causes for the bleeding via personal history, family history, physical examination, gynecologic examination, laboratory studies focused on coagulation and thyroidstudies, and pelvic imaging. It is also important to rule out pregnancy. Treatment options include combined oral contraceptives, progesterone, non-steroidal anti-inflammatory drugs (NSAIDs), tranexamic acid, GnRH analogues, danazol and levonorgestrel-releasing intrauterine devices.

Warfarin is not indicated in the management of abnormal uterine bleeding. However, if a patient is taking warfarin during episodes of abnormal uterine bleeding, it would be essential to assess coagulation parameters to ensure that the effect is within the therapeutic window.

Iron supplementation is indicated in the treatment of microcytic anemia. It would not be indicated for this patient with a hemoglobin level greater than 12 g/dL and lacks symptoms secondary to anemia.

Packed RBCs are not necessary at this point for this patient since she has a hemoglobin level greater than 12 g/dL and lacks symptoms secondary to anemia.

Nonsteroidal anti-inflammatory drugs, such as aspirin and ibuprofen, are commonly used as pain relievers. The patient does not report any pain, so ibuprofen would not be indicated.

Major takeaway
Tethered cord syndrome involves the attachment of the spinal cord to a part of the vertebral canal and subsequent spinal cord stretching with growth. TCS is associated with Ehlers-Danlos syndrome, Klippel-Feil syndrome, Arnold-Chiari malformation, and other spinal cord dysraphisms.
Main explanation
Tethered spinal cord syndrome (TCS) can occur independently (primarily anatomical) or as a complication of the closed spinal dysraphias. It is a stretch induced dysfunction of the caudal spinal cord and conus due to attachment of the filum terminale to immobile caudal structures. Normally, the filum terminale is viscoelastic in nature. In adults, the main symptoms of tethered spinal cord syndrome are back pain, leg pain, and scoliosis. These symptoms may be difficult to distinguish from many other causes of leg and back pain. The earliest sign of motor dysfunction in older children or adults is weakness of ankle dorsiflexion.

TCS is associated with Klippel-Feil syndrome, Arnold-Chiari malformation, Ehlers-Danlos syndrome, and spinal cord dysraphisms. It is recommended that if patients are diagnosed with TCS that they are then screened for all of these conditions.

Korsakoff syndrome is a chronic memory disorder caused by vitamin B1 (thiamine) deficiency. Patients with this condition characteristically have a history of alcohol use disorder.

Muscular dystrophy is a hereditary condition marked by the progressive wasting of muscles. There are various types of muscular dystrophy, but most concern the structure of the muscle and not neurologic connections.

Thymoma is a condition characteristically associated with myasthenia gravis patients. Patients with myasthenia gravis should be screened and watched for the development of this tumor.

Wernickes encephalopathy is a condition characteristically of patients with a history of alcohol use disorder. It may manifest as confusion, vomiting, abnormal gait, and nystagmus.

Although asthma is very common in children and can lead to chronic cough. Asthma is commonly associated with eczema and allergies. Diagnosis is done with pulmonary function testing showing a return of normal function with administration of bronchodilaters.

Kartagener syndrome is an hereditary autosomal recessive disease caused by a defect in ciliary dynein. This results in immotile cilia. The classic symptoms of this condition are bronchiectasis, infertility, and dextrocardia.

Major takeaway
Patients with cystic fibrosis may have chronic cough, pancreatic insufficiency, meconium ileus, and recurrent pneumonias. Cystic fibrosis occurs as a result of a defective chloride ion transporter leading to thick respiratory secretions.
Main explanation
In this clinical vignette, the patient displays many of the classic symptoms of cystic fibrosis. Patients with cystic fibrosis will have foul smelling diarrhea, recurrent pulmonary infections, chronic cough, and failure to thrive. Other symptoms include breathing difficulties, joint pain, and lack of facial hair. Cystic fibrosis is the most commonly inherited disease among Caucasians (especially those of Northern European descent). It is an autosomal recessive disorder resulting in a faulty version of a chloride channel protein known as the cystic fibrosis transmembrane conductance regulator (CFTR). This results in the production of excessively thick mucus in the respiratory tract, pancreatic ducts, and biliary tree. The normal version of this protein helps transport chloride ions out of exocrine gland cells. In this process, water usually follows by osmosis, thus decreasing the viscosity of mucus secretions from these exocrine cells. However, in cystic fibrosis, the faulty CFTR protein is not able to adequately pump chloride out through the cell membrane. Hence, the mucus secretions from exocrine cells are excessively viscous and thick. Cystic fibrosis patients are therefore subjected to repeated bouts of lower respiratory infections, pancreatic insufficiency, and failure to thrive.

Cardiac defects, abnormal facies, thymic dysplasia, and hypocalcemia are hallmark symptoms of DiGeorge syndrome. DiGeorge syndrome is a genetic disorder characterized by the deletion of 22q11.2.

Patients with cystic fibrosis commonly get pulmonary infections. However, classically cystic fibrosis patients will have either S. Aureus or P. aeruginosa infections depending on age (less than 20 is Staph, greater than 20 is Pseudomonas). A viral infectiontypically does not cause malabsorption and failure to thrive.

Antisocial personality disorder is a cluster B personality disorder. Patients with antisocial personality disorder show a disregard for others and typically have violations with the law. Antisocial personality disorder must be diagnosed after the age of 18 years old and begins in childhood as a conduct disorder.

Patients with attention deficit hyperactivity disorder have symptoms of problems listening, difficultly paying attention, easily distracted, forgetful, talking excessively and/or fidgeting. The onset is typically before 7-years-old. Patients are not aggressive toward others and/or animals and destructive of property as seen in this case.

Individuals with a conduct disorder have numerous antisocial activities such as lying, stealing, running way, physical violence, sexually coercive behaviors, and destruction of property. Children and adolescence with conduct disorder will have defiant behavior toward everyone. In oppositional defiant disorder the poor behavior is directed toward authority figures.

Major takeaway
Oppositional defiant disorder (ODD) is defined by the DSM-5 as a recurrent pattern of angry/irritable mood, argumentative/defiant behavior, or vindictiveness lasting at least 6 months and is not due to a mood or psychotic disorder.
Main explanation
Oppositional defiant disorder is characterized by a pattern of angry/irritable mood, argumentative/defiant behavior or vindictiveness lasting at least 6 months and outside of the normal range of the individual’s development level. Generally onset is usually before the age of 8-years-old. Problems initially start at home, and then may progress to affect relationships with teachers such as in this case. Generally children will have conflicts with authority figures and not peers.To fulfill the diagnosis, an individual must have 4 of the following: often loses temper, often argues with adults, often actively defies or refuses to comply with adult requests, often deliberately annoys others, often blames others for his or her mistakes or poor behavior, often touchy or easily annoyed, often angry or resentful, often spiteful or vindictive. Symptoms are almost always present at home and may or may not be present in the community and at school. Many times children with oppositional defiant disorder have a previous diagnosis of attention deficit hyperactivity disorder. Symptoms may improve, especially if the child receives treatment, which includes individual psychotherapy, parenting skills training, and treatment of underlying attention deficit hyperactivity disorder if necessary. At times the disorder may progress to conduct disorder.

Schizoid personality disorder is a cluster A personality disorder. Patients will be detached from others and have little desire for close relationships. People with this disorder prefer to be alone and take pleasure in few activities. This would not be diagnosed until adulthood, similarly to antisocial personality disorder.

Cystathionine synthase deficiency is the most common cause of homocystinuria, an autosomal recessive disease which leads to mental retardation, hypercoagulability, and Marfanoid habitus.

Autoimmune-mediated lymphocytic destruction of the pancreatic beta islet cells leads to diabetes mellitus type 1. These patients are prone to diabetic ketoacidosis and require insulin.

Folate acid plays an important role in the function of dihydrofolate reductase in DNA synthesis. Folic acid deficiency is common in alcoholics and is characterized by megaloblastic and macrocytic anemia.

Major takeaway
Pernicious anemia is an autoimmune destruction of gastric parietal cells. Laboratory testing will show anti-parietal or anti-intrinsic factor antibodies. These patients are at risk for vitamin B12 deficiency.

Main explanation
Pernicious anemia is an autoimmune destruction of gastric parietal cells. These patients will often have anti-parietal or anti-intrinsic factor antibodies. As with most autoimmune conditions, females are more commonly affected than males. Because vitamin B12 require the intrinsic factor produced by parietal cells to absorb vitamin B12, these patients are at risk for vitamin B12 deficiency. B12 deficiency is characterized by a megaloblastic macrocytic anemia, along with gastrointestinal and neuropsychiatric symptoms such as irritability or a characteristic reversible dementia. It can also cause subacute combined degeneration is a relatively rare manifestation of vitamin B12 anemia which causes a loss of distal proprioception, spastic limb weakness, and ataxia. These patients should receive regular injections with vitamin B12.

Syringomyelia is a cyst which develops within the spinal cord and is commonly associated with the Arnold-Chiari malformation. Syringomyelia is characterized by a bilateral loss of pain and muscle weakness.

Major takeaway
This patient’s presentation with echolalia (i.e., imitating the mother) and stereotyped muscle contractions (i.e., eye blinking, repetitive frowning, head shaking, and throat clearing) are suggestive of a tic disorder.
Main explanation
This patient’s presentation with echolalia (i.e., imitating the mother) and stereotyped muscle contractions (i.e., eye blinking, repetitive frowning, head shaking, and throat clearing) are suggestive of a tic disorder. Tic disorders are characterized by recurrent and stereotypedmuscle contractions. In general, tics can be classified as: (1) motor tics (twitches of the face, blinking), and (2) phonic tics (grunts, coprolalia, echolalia). According to the DSM-V, tic disorders can be broadly classified into three categories: transient tic disorders, chronic motor or vocal tic disorders, and Tourette syndrome.
This patient most likely has Tourette syndrome. Patients present with stereotyped motor and vocal tics and behavioral symptoms, such as attention deficit hyperactivity disorder or obsessive compulsive disorder.
Tic disorders are common among children and adolescents between 2 and 15 years of age. In the majority of patients, tics will disappear with time. Patients with tic disorders may experience an irresistible urge to express tics but can voluntarily suppress them for short periods. Medical therapy is indicated when tics interfere with social interaction or quality of life, or if they cause the patient physical pain.
The mainstay therapy for Tourette syndrome centers around education, behavioral therapy, guanfacine, clonidine, and medical therapy tailored to the patient’s presentation.

Huntington disease is an autosomal dominant inherited movement disorder characterized by a general lack of coordination and an unsteady gait. Patients initially present with jerky, random, and uncontrollable movements. However, the history of attention deficit disorder, echolalia, and stereotyped movements are more indicative of a tic disorder.

Although the family history indicates the possibility of the patient having a movement disorder. Young-onset Parkinson disease is characterized by resting tremor, slowness of movement, and difficulty with walking. None of the aforementioned signs are true in this patient.

Rett syndrome is a rare genetic postnatal neurological disorder of the gray matter of the brain. It almost exclusively affects females. The clinical features include small hands and repetitive stereotyped hand movements, none of which are present in this patient.

Myoclonic dystonia is a movement disorder that induces spontaneous muscle contraction causing abnormal posture. Patients present with spontaneous jerking motions in distal limbs (more commonly). However, history of attention deficit disorder, echolalia, and stereotyped movements are more indicative of a tic disorder.

Dissociative identity disorder (or multiple personality disorder) is a mental disorder characterized by the presence of two or more distinct identities or personality states. This condition is generally accompanied by memory impairment for important information not explained by ordinary forgetfulness. However, none of these characteristics are seen in this patient.

Borderline personality disorder is a cluster B personality disorder characterized by a pattern of unstable relationships, unstable sense of self, and unstable emotions. Although patients have emotional outbursts, such as crying or laughing, there is usually an underlying cause. Here, however, there is no underlying cause for this patient’s outbursts.

Treatment-resistant depression is a type of major depressive disorder, in which patients do not respond adequately to appropriate courses of at least two antidepressants. Here, however, the patient has a medical history of bipolar disorder and there are no prompts in the stem about any kind of treatment response.

Schizophrenia is a chronic mental disorder characterized by periods of psychosis, disturbed behavior, and a decline in functioning lasting over 6 months. Although patients may have odd behaviors, such as uncontrollable laughing. Here, however, the history of brain injury, in addition to, laughing episodes should be suggestive of pseudobulbar affect.

Major takeaway
Pseudobulbar affect is a type of emotional response characterized by involuntary crying or uncontrollable episodes of crying or laughing that is generally caused by brain injury or a neurologic disorder.
Main explanation
The patient in the vignette is experiencing pseudobulbar affect. Pseudobulbar affect is a type of emotional response characterized by involuntary crying or uncontrollable episodes of cryingor laughing without an apparent reason, that is generally caused by brain injury (i.e., history of traumatic brain injury) and neurologic disorders. It may be a symptom of amyotrophic lateral sclerosis (ALS), dementia, multiple system atrophy, or others.

Unlike depression, patients with pseudobulbar affect often have laughing or crying episodes that can last minutes or seconds, that have no voluntary control, no behavioral changes (vs. apathetic mood in depressed patients), and no self-misperceptions (vs.negative view of self in depressed patients).

The pathogenesis of pseudobulbar affect is not fully understood. However, treatment is usually directed towards decreasing the frequency and severity of the uncontrollable laughing or crying episodes.

The pharmacological treatment usually involves the serotonergic action of serotonin reuptake inhibitors and tricyclic antidepressants, both of these treatments appear to be the most significant therapeutical options to treat pseudobulbar affect.

Fear of weight gain is a prominent reason for restricted food intake by people with anorexia nervosa. This leads to a BMI usually below 18 kg/m2. The fear often increases despite continued weight loss.

DSM-5 criteria for bulimia nervosa include recurrent episodes of binge eating followed by compensatory behavior to prevent weight gain, occurring on average 1 or more times per week for three months.

Many eating disorders, but especially anorexia nervosa, are characterized by a persistent, grossly distorted perception of body weight and shape

Major takeaway
Avoidant/restrictive food intake disorder usually begins in childhood. The eating behavior leads to nutritional deficiency, such as iron deficiency anemia, and supplementary feeding may be required to meet nutritional needs.
Main explanation
Avoidant/restrictive food intake disorder is defined as an eating disorder in the DSM-V. The following are necessary criteria for diagnosis:
1. Restricted food intake based on lack of interest in eating, intolerance of a sensory characteristic of food, or a conditioned negative response associated with food (e.g. following an episode of choking). This leads to significant weight loss, nutritional deficiency, and failure to thrive.
2. The food intake pattern is not due to lack of available food.
3. Body perception is not distorted, and neither anorexia nor bulimia nervosa is the primary diagnosis.
4. General medical conditions (eg. allergy, gastrointestinal disease) and other psychiatric illnesses are ruled out.

Retrospective studies in the U.S. and Canada estimate that 5-15% of pediatric patients in eating disorder programs have avoidant/restrictive food intake disorder. There is a higher prevalence of males (20-30%) compared to anorexia and bulimia.

Patients with autism spectrum disorder (ASD) may exhibit extreme sensitivity to sensory aspects of food such as flavor, color, smell, and texture. This patient does not display characteristics of ASD in his communication.