Prototypic Patients

Question 1

Patient has been “volun-touring” in a developing country for a few months, and just got back. Presents to clinic with bloody diarrhea for the past two weeks, and abdominal pain. His labs show inflammation and elevated LFTs. Sigmoidoscopy shows ulceration in the colon.

Answer 1

Entamoeba histolytica

Cyst is infective, has four nuclei. Trophozoite has one nucleus. Life cycle involves ingesting the cysts, which mature into trophozoites, which then chew through the intestinal wall, causing FLASK-SHAPED ulcers filled with chewed up cell byproducts. The trophozoites can be seen at the edge between necrotic and healthy tissue.

Can cause systemic infection with lesions in the liver - ALA = amoebic liver abscess, filled with brownish-red gunk that looks like anchovy sauce. Can also cause peritonitis and an intestinal mass called an amoeboma.

Entamoeba dispar looks the same, but is non-pathogenic.

Dx: stool O&P, sigmoidoscopy.

To: metronidazole if symptomatic, lodoquinol or paramomycin if not symptomatic. Liver abscess responds to drugs 90% of the time (surgery if not responding).

Question 2

A man who has been traveling in central Africa presents with fever and some altered mental status. He is not acutely sick. He has an ulceration on his arm. On peripheral blood smear, flagellated Protozoa with what looks like a second nucleus are noted.

Answer 2

Trypanosoma brucei gambiense (more indolent and mild form)

This is a kinetoplastid, so trypomastigotes in blood will be small flagellated protozoa with a kinetoplast (collection of mitochondrial DNA that’s so big that it looks like a small second nucleus). Amastigotes will be found in tissue.

Carried by tsetse fly. Bite leads to infection of human with trypomastigotes, which disseminate through the body.

Dx: blood smear to look for trypomastigotes, CSF or tissue sample to do the same, history (esp. Epidemiology), fever, lymphadenopathy, behavioral changes, altered mental status.

Tx: if early and acute w/o CNS involvement - give suramin. If chronic stage with CNS involvement, give melarsoprol. Treatment doesn’t work very well, though.

Question 3

A 6 y/o F presents to the pediatric ED. She is unresponsive. Her mother reports that two days ago, the girl went to a birthday party where she swam in the hot tub, and despite her mom’s warnings, went underwater to play with the jets. The next morning she woke up with a headache and was lethargic, and got worse progressively over the course of the day. This morning, the mother could not wake her daughter up.

Answer 3

Naegleria fowleri, causing acute PAM (primary amoebic meningoencephalitis)

This is a BAD, acute, fulminant disease that causes necrosis. Frequently diagnosed on autopsy when trophozoites are found in thee CSF.

Associated with water pressure introducing parasites into the nasal passages. The parasites climb up through the cribiform plate into the CNS.

Tx: Amphotericin B

Question 4

While working at a refugee camp in the Middle East, you see a patient present to your clinic who seems very sick. He reports that he keeps getting bitten by sand flies. You order some labs, and you find that his WBC count is very low, and his serum is positive for HIV RNA, and he does not have TB.

Answer 4

Disseminated leishmaniasis

Transmitted by sand fly, intracellular parasite. Host defense is dependent on T cells, so in individuals with diminished Tc immunity, visceral disseminated disease can occur. These patients will have a negative skin test, high Abs, and a high parasite load, especially in the bone marrow.

Dx: Amastigotes found on biopsy

Tx: Amphotericin B

Question 5

Andy is a 20-year-old collegiate soccer player who presents to Student Health for a 2-month history of cough that won’t go away. His PMH and FH are non-contributory. On physical exam, lung sounds in the apex of the right lung are diminished, and CXR reveals an 18-cm-long mediastinal mass. A needle biopsy of the mass reveals some binucleate “owl-eye” cells with prominent red nucleoli, surrounded by fibrosis and other WBCs, including eosinophils.

Answer 5

Hodgkin Lymphoma

An aggressive B-cell lymphoma with an overall good prognosis with immediate and aggressive treatment.

Pathology: characteristic Reed-Sternberg cells - “owl-eye” binucleate cell, way bigger than normal, prominent nucleoli. May also just have atypical Hodgkin’s cells which are oversized neoplastic cells. However, most of the tumor/LN is filled with fibrosis, eosinophils, etc, and the actual malignant cells make up a minority of the tumor volume.

B symptoms (night sweats, fever, etc), anemia of chronic disease, LAD, may have a mediastinal mass, varying other symptoms depending on the disease presentation.

Question 6

18yoM presents to clinic with 2 weeks diarrhea, stools floating in the toilet. Prior to these symptoms he was hiking in the mountains for a week with friends. Complains of fatty, malodorous stools, bloating, gas, and abdominal pain.

Answer 6

Giardia lamblia

Cyst is infective - 4 nuclei. Trophozoite has pear shape, 2 nuclei, four pairs of flagella.

Dx: stool O&P, but EIA is a good test (also test for cryptosporidium)

Tx: metronidazole (paramomycin in pregnancy)

Question 7

A 47-y/o woman presents to the ED after being sent there by her PCP, who is concerned about a new-onset murmur. She is from Honduras originally, and moved to the US 15 years ago. She now works as a CNA. PMH is significant for an incident in her early 30s before she moved to the US where her eye swelled up for about a month. FH includes no history of cardiac issues. ECG shows second-degree heart block, and echocardiogram reveals cardiomyopathy.

Answer 7

Trypanosoma cruzi - Chagas’ Disease

This is a kinetoplastid, with a large accumulation of mitochondrial DNA known as a kinetoplast that looks almost like a second nucleus. Trypomastigotes are flagellated Protozoa that are found in the liver, blood, spleen, LNs, etc. Amastigotes replicate in tissues.

From the bite of kissing bugs, triatamine bugs, etc - they bite you, defecate on the skin, and then scratching allows the parasite to enter the tissues.

Most common cause of heart disease in areas where it is endemic - specifically South and Central America.

Acute stage of the disease is characterized by low-grade fever for 1-4 months and Romana’s sign (swelling of one eye), but may be asymptomatic. 10-20 years later, patients present with cardiac issues and intestinal issues, as well as megasyndromes (megacolon, hypertrophic cardiomyopathy, etc).

Dx: blood and tissue samples

Tx: Treat acute disease with nifurtimox or benznidazole. Treat chronic disease symptomatically. Treatment isn’t super effective so prevention (nets, bug spray, etc) is more important.

Question 8

A 28-year-old sexually active woman presents to your clinic with pelvic pain. She reports pain on intercourse, low-grade fever, and purulent vaginal discharge. She has had four male sexual partners within the past year. She uses barrier protection “some of the time” and has a Nexplanon implant. On exam, you observe cervical, adnexal, and uterine tenderness. She has no irregular bleeding and no history of any reproductive disorders. Her menstrual cycles are regular, without any unusual pain. She says she had gonorrhea once when she was sixteen, but it was treated then.

Answer 8

Pelvic Inflammatory Disease - a combination of these symptoms resulting from polymicrobial infection, typically with a combo of chlamydia and/or gonorrhea and/or normal vaginal flora. This is a clinical diagnosis and requires a high index of suspicion.

Treat immediately with broad-spectrum antibiotics, and abstain from sex until treatment is done. These patients will also need screening.

Future risks include infertility, ectopic pregnancy, and chronic pelvic pain.

Question 9

A 30-year-old man presents to clinic complaining of a non-painful ulceration on his lip that has been around for three weeks but still is not healed. He was last sexually active 6 weeks ago with a male partner, but has had multiple male and female partners over the past year. On exam you observe an ulcer on the inside of his lip, as well as noticing some cervical lymphadenopathy.

Answer 9

Primary syphilis - treponema pallidum

Treponema pallidum is a spirochete. It causes disease via obliterative endarteritis (especially in later stages of the disease). It is spread via sex, close skin-to-skin contact with lesions, and congenitally. It has a 3-90 day incubation period.

Primary syphilis is defined as a painless chancre at the site of inoculation, often with LAD, that takes 2-8 weeks to heal.

Testing for syphilis: VDRL and RPR are used as screening tests. These tests will also show when therapy has been successful, and can be used to track effectiveness of therapy. Tests that include a T are treponemal tests. These will always be positive when a patient has a history of infection, and will not turn negative after therapy. These are used to confirm results found by VDRL and RPR.

Tx: penicillin! If allergic, desensitize the patient, and then give penicillin. If pregnant, give penicillin.

Question 10

A 26 year old man presents to the ED with a morbiliform rash that developed on his extremities, including palms and soles. He has had fevers, myalgia, nausea and vomiting, headaches, and inflamed conjunctiva for the past few days, as well as swelling around his eyes. He appears acutely ill. He has no significant PMH or FH. He is up to date on his vaccinations. He returned about 10 days ago from a hiking trip in Kentucky, during which he felt fine.

Answer 10

Rickettsia rickettsii - Rocky Mountain Spotted Fever

Question 11

Jamie is a 17-year-old girl who has been referred to your endocrinology practice for weight gain and irregular menses. You evaluate her and begin treatment for PCOS. However, while you are taking her social history, she confides in you that she has recently become sexually active with a girl from her high school class. She says that she didn’t want to tell her pediatrician, because she doesn’t want her mom to find out. She wants to know whether she should be screened for STIs. What do you tell her?

Answer 11

Yes! Screening for STIs is recommended for all sexually active women younger than 25.

Question 12

A sexually active 29-year-old man presents to clinic with a painful ulcer on his penis. It has ragged edges and bleeds easily. On exam you note a grossly enlarged inguinal lymph node.

Answer 12

Chancroid - caused by haemophilus ducryei (GN coccobacillus)

Clinical diagnosis based on presentation.

Tx: azithromycin or ceftriaxone.

Question 13

50y/o M returning from a trip to Thailand presents to your outpatient clinic with a history of fever. He has been spiking high fevers with chills about every 48 hours. He feels fatigued and is concerned about what is going on.

Answer 13

Malaria infection - fever in a returning traveler is malaria until proven otherwise

This infection is probably due to Plasmodium vivax (tertian fevers - every 48 hours).

Transmitted by mosquito. Trophozoites go to the liver, and replicate in hepatocytes. When the schizonts rupture, they spread to RBCs. Merozoites replicate in the RBCs (now the schizonts), the RBC ruptures, and releases them. Mosquitos ingest the gametocytes, and continue to spread the infection.

Dx: gold standard is a blood smear, but this requires an expert lab. Other assays are more commonly used, especially rapid dipstick assays in the US.

Tx: Quinine drugs

Question 14

A 73-year-old woman is in your clinic for an annual physical. Her exam is normal, and you have no concerns for her health. As you start to walk out the door, though, she asks you, “What about these spots on my hands? What are they? Could they ever turn into skin cancer?” When you look at her hands, you see evenly pigmented, smooth, broad brown spots on the backs of her hands and forearms. There are also some on her face and the part of her chest that her shirt does not cover. How do you answer her?

Answer 14

These are solar lentigines.

Normal benign overgrowth of epidermis - not moles! Occur in a photo distributed pattern. These are not harmful.

Question 15

You are a renowned pathologist at a prominent teaching hospital. A 25-year-old medical student shows up at your office after she noticed that she had a high WBC with elevated numbers of leukocytes after doing a hematology lab. She is very worried that something serious might be going on, as she has felt fatigued and feverish for the past week and has had significant posterior cervical lymphadenopathy. She helpfully brought you the blood smear that she prepared in class. When you look at the smear under your microscope, you see numerous lymphocytes that appear to be stretched out up against the surrounding RBCs. What do you suspect is going on?

Answer 15

Reactive leukocytosis, probably due to EBV (or less likely, CMV) infection.

Question 16

Petra is a 26-year-old woman who presents to clinic with pain and swelling in her fingers and hands. On exam she has swollen and deformed joints in her fingers. You observe nail pitting as well as erythematous plaques with fine micaceous scale behind both her ears and on her scalp. When you ask for her past medical history, she tells you that she has struggled with her weight and was just diagnosed with type 2 diabetes and metabolic syndrome. You also observe enthesitis of her Achilles tendons bilaterally. You obtain an XR of her hands and observe erosions.

Answer 16

Psoriatic arthritis

40% are HLA-B27+. This may present before a diagnosis of psoriasis in 30% of patients. Characterized by frequently peripheral SpA, but 50% have often unilateral axial SpA.

The arthritis is often asymmetric, often polyarticular, and may progress to arthritis mutilans. Common additional findings include enthesitis, dactylitis, nail psoriasis (pitting), and increased frequency of MetS, T2DM, and hyperuricemia/gout.

Treat with NSAIDs, SSZ, TNF inhibitors, and PT plus aprelimast (PDE4 inhibitor) that’s good for non-erosive arthritis and psoriasis. If the patient fails two TNF inhibitors, you can use ustekinumab (P40 mAb) or secukinumab (IL-17 mAB).

Question 17

Traveler from East Africa presents to the ED with high fever and altered mental status. She has been in the US for one week. There is a large ulcer on her arm. She is very sick and seems to be getting worse quickly.

Answer 17

Trypanosoma brucei rhodiense (East African Sleeping Sickness)

Severe, fulminant infection! Worse than the gambiense form.

This is a kinetoplastid, so trypomastigotes in blood will be small flagellated protozoa with a kinetoplast (collection of mitochondrial DNA that’s so big that it looks like a small second nucleus). Amastigotes will be found in tissue.

Carried by tsetse fly. Bite leads to infection of human with trypomastigotes, which disseminate through the body.

Dx: blood smear to look for trypomastigotes, CSF or tissue sample to do the same, history (esp. Epidemiology), fever, lymphadenopathy, behavioral changes, altered mental status.

Tx: if early and acute w/o CNS involvement - give suramin. If chronic stage with CNS involvement, give melarsoprol. Treatment doesn’t work very well, though.

Question 18

30 y/o M presents to clinic with 2-month history of non-healing skin ulcer on his arm. He is in the US Marines and has just returned to the states after an 18-month deployment in Iraq. He is otherwise healthy. Biopsy of the lesion reveals unicellular eukaryotes that are not flagellated and have a nucleus and a smaller dark body of material in the cells.

Answer 18

Leishmaniasis

Intracellular pathogen, does not have trypomastigotes. Can be localized to skin, as in this patient, or can cause visceral disease.

Dx: Amastigotes found on biopsy. Cutaneous disease will have a positive skin test, and low antibodies.

Tx: Amphotericin B

Question 19

A 40-year-old male patient presents to your office with painful urinary discharge and urinary frequency and urgency. He denies hematuria. He is sexually active, and has been with his current partner for about two weeks. His partner is female and is on OCPs. Neither partner uses barrier protection during sexual intercourse. When you do a gram stain of the discharge, you do not see any organisms.

Answer 19

Most likely an infection with chlamydia, the #1 bacterial STD in the US. While incidence is highest among teens and young adults, anyone could get it.

Different serotypes include A-C (ocular chlamydia), D-K (urethritis/cervicitis), and L1-L3 (LGV). It does not stain on gram stain!

7-14 day incubation. 40% of males could be asymptomatic. Symptoms frequently include dysuria and a white-grey discharge.

Treat with azithromycin or doxycycline.

Question 20

You are following a 43-year-old female after she has received a renal transplant. Her recovery has gone well and she has had no symptoms of rejection. However, she now presents to the ED with high fever, cough, dyspnea, and hemoptysis. She feels very ill. She reports that she has had diarrhea and abdominal pain as well, and while she has used a steroid inhaler for the wheezing that she’s been experiencing, the inhaler actually seems to be making it worse. CXR shows diffuse bilateral pulmonary effusions. Blood cultures show GN bacteria. Her CBC is significant for very high eosinophil counts. Inpatient ceftriaxone clears her blood of the bacterial infection within a few days, but her pulmonary symptoms remain.

Answer 20

Strongyloides

Nematode that lives in the intestine but can disseminate into bloodstream in the immunosuppressed, carrying GN bacteria from the intestine and causing bacteremia and/or meningitis. It can also migrate to the lung, where it matures before going to the gut. This can cause Loeffler’s pneumonia symptoms.

It doesn’t have eggs - you will see larva in stool and sputum. The infective form is filariform larva in the soil, which penetrate the skin.

It is important to check for this before transplant!

Presentation includes diarrhea, pain, malabsorption, eosinophilia, and asthma that worsens with steroids.

Dx: sputum or stool exam for larva, ELISA

Tx: ivermectin or albendazole

Question 21

21-y/o woman presents to Student Health during the first week of the school year with flu-like symptoms, including fever, chills, sweating, and fatigue. Her history is significant for a camping trip in upstate New York with her friends the week before school started. She says she found a tick on her, but pulled it off. She denies any rash or skin changes. You order some labs and find that her hematocrit is low.

Answer 21

Babesiosis - transmitted by Ixodes scapularis, the same tick that transmits Lyme.

Life cycle of babesia doesn’t even require humans. Tick bites, parasite infects RBCs, which lyase and release parasites, and the tick ingests them.

Dx: blood smear.

Tx: quinine + clindamycin

Question 22

A patient presents to the emergency room vomiting blood. He is severely hypotensive. On exam he has ascites, red conjunctiva, and edema in his legs. Lung sounds demonstrate fine crackles, and CXR shows bilateral pleural effusion. His wife says that they were just traveling across Asia, and right after they got back, he developed a fever. It is now a few days after the onset of symptoms, and he is very acutely ill.

Answer 22

Dengue

RNA virus covered in a lipid coat that causes hemorrhagic fever. The target organ is vascular endothelium, leading to end-organ damage, but the most severe damage is from the innate immune response. When the virus spreads to macrophages and DCs, it leads to tons of inflammatory mediators causing procoagulant activity, and release of tissue factor, causing the potential for DIC.

Hemorrhagic fevers tend to present with prodromal illness of high fever, malaise, headache, weakness, dizziness, myalgias, arthralgias, N/V/D. More specific prodromal symptoms include conjunctival injection (red eyes), pharyngitis, rash, edema, hypotension, shock, and bleeding from mucous membranes. WHO criteria for diagnosis is fever over 101 for less than 3 weeks, severe illness, no predisposition or alternative cause and 2+ hemorrhagic symptoms.

Dengue is characterized by an initial febrile phase, followed by a critical phase with hypotension, ascites, pleural effusions, and GI bleeds. If the patient survives this, the next phase is a recovery phase, characterized by altered LOC, seizures, itching, and bradycardia.

Tx: supportive care - correct coagulopathies, avoid anti-platelet drugs and IM injections. Ribavirin prophylaxis is helpful in high-risk contacts.

Question 23

A 19-year-old woman presents to the pediatric clinic with her two-day-old infant. This is her first child. She and the child are uninsured and she has received no prenatal care. The infant was a home birth. She is concerned because her baby has bloodshot eyes and seems inconsolable.

Answer 23

Neonatal conjunctivitis from gonorrhea

Presents within 2-3 days of birth (in contrast, if it’s from chlamydia, it presents within 5-12 days of birth). If untreated, it can lead to blindness.

Gonorrhea in the newborn can also cause scalp abscesses and meningitis.

Chlamydia in the newborn can cause neonatal pneumonia.

Prevent gonorrheal conjunctivitis with erythromycin ointment in the eyes at birth.

Normally prevention is accomplished by screening and treating the mother during pregnancy.

Question 24

A 31-year-old male with a history of HIV infection controlled with combination antiretroviral therapy presents to clinic for a lesion on his left ear. The lesion is a well demarcated thin plaque on the top of his ear. The edges are somewhat erythematous and indurated. There is a little bit of fine scale. You send the patient for Mohs surgery to excise the lesion with as small a scar as possible, given the location on his ear.

Answer 24

Squamous cell carcinoma

Second most common skin cancer (although 3x more common than BCC in immuno suppressed patients).

Increased risk of metastasis if lesions are on the lips, ears, or mucosa, as well as with chronic inflammation.

This may progress from actinic keratosis to SCC in situ to fully fledged invasive SCC. In situ is only involving the epidermis. Invasive SCC goes down into the dermis or below, producing an indurated erythematous plaque or nodule that may become ulcerated or scaly.

Treatment: excise low-risk lesions, and excise high-risk lesions via Mohs surgery. There is a poor outcome if this cancer metastasizes.

Question 25

A patient presents to your clinic with cough, fever, malaise, and a rash all over the backs of his thighs. On CBC, he is anemic and also has eosinophilia. Stool ova and parasite reveals round oval eggs.

Answer 25

Hookworm - Ancylostoma duodenale or Necator americanus

Both organisms latch onto the wall of the intestine, sucking blood and causing anema. Ancylostoma has one pair of cutting plates. Necator has two pairs of teeth.

It causes anemia, and Loeffler’s pneumonia. Differential for Loeffler’s pneumonia is ascaris, hookworm, strongyloides.

Dx: recovering the eggs in stool. Shaped like round ovals.

Tx: albendazole, mebendazole

Question 26

A 31-year-old female presents to your clinic complaining of vaginal discharge. On pelvic exam you notice a small amount of mucopurulent cervical exudate, and bleeding from the cervical os when you gently pass a swab through it. She is sexually active with multiple partners and uses barrier protection “most of the time,” and has a copper IUD.

Answer 26

Cervicitis, most likely due to chlamydia or gonorrhea. The presentation for both is very similar.

Work up includes NAAT (PCR) as the key diagnostic test, as well as a gram stain of the discharge. The patient must be evaluated for PID, as that can lead to decreased fertility and risk of ectopic pregnancy. She should also receive a pregnancy test (even though she has an IUD, it might be a good idea).

Treat gonorrhea with ceftriaxone plus azithromycin or doxycycline.
Treat chlamydia with azithromycin or doxycycline.

Question 27

In your pathology lab, you are examining a sample of vaginal discharge from a 20-year-old female patient. The information that the nurse practitioner gave you tells you that this patient was complaining of a fishy-smelling whitish-grey discharge. What do you expect to see in your sample?

Answer 27

This is bacterial vaginosis, most likely. You will see clue cells on exam, which are epithelial cells with coccobacilli coating them. “A clue for BV”

Diagnostic criteria: 3/4 of the following. Whitish grey discharge coating vaginal walls; strong odor when prepped with KOH; ph>4.5 (more alkaline than usual); presence of clue cells.

This is usually due to a loss of H2O2-producing lactobacillus species from the vagina, often after a course of antibiotics. Gardnerella and other anaerobes increase.

No inflammation of vaginal walls or cervix, but this does put you at increased risk of other STDs.

Tx: metronidazole or clindamycin. Treat all pregnant women! The male partner does not need tx.

Question 28

An 18-year-old female and her mother present to your dermatology clinic. The girl is concerned about a mole on her back that she has had for years. While shopping for prom dresses, the mother noticed that the mole had grown in size somewhat, and had some irregular coloration, with a darker area in the center. The mole is normally covered up with clothing, and the girl always wears sunscreen when she has her back exposed. You decide to excise the nevus. On histopathology, you observe abnormal cells that are clustered in one area of the epidermis. They are not proliferating radially or vertically through the epidermis.

Answer 28

This is a dysplastic nevus, although histologically it looks just like melanoma in situ.

Dysplastic nevi look clinically atypical. They are probably not precancerous, but look just like melanoma in situ on histopathology. The presence of lots of dysplastic nevi indicates increased risk of melanoma.

Tx: treat these just like melanoma in situ. Excision, followed by histopathology. Follow-up skin exams yearly.

Question 29

A 40-year-old woman comes to clinic for her annual physical. Incidentally during the pelvic exam, you notice a papular ulcer on her labia minora. She reports that she has not noticed it, and has had no pain there. There is also swelling of the inguinal LNs on the right side, specifically with swelling above and below the inguinal ligament.

Answer 29

LGV - Chlamydia trachomatis serogroup L1, L2, L3

Presents as a painless papule ulcer and bubo. The groove sign refers to LN swelling above and below the inguinal ligament.

Diagnosed clinically.

Tx: doxycycline

Question 30

A 31-year-old male presents to the ED, complaining of a hot, painful, swollen knee. He has also had some rash on his arms for the past week. Looking through his chart, you find that he has a complement deficiency. He was also assessed at urgent care for painful urination and penile discharge last week, although he never filled his prescription for antibiotics. You immediately perform a joint aspiration and send it for gram stain. The results of the gram stain show gram-negative diplococci.

Answer 30

Disseminated gonorrhea: gram-negative diplococci

10% of men are asymptomatic with gonorrhea infection and do not present with symptoms of urethritis or cervicitis. They can, however, present with disseminated gonorrhea. Complement deficiency increases the risk of disseminated gonorrhea.

Question 31

Lucy is a 62-year-old woman who you follow for her rheumatoid arthritis. She recently couldn’t achieve good disease control with DMARDs and you switched her to adalimumab, which has kept her RA under control. She presents to clinic with a severe cough and crippling fatigue that came on two days ago quite severely and suddenly. She reports no history of fever. You order a CXR and find left lower lobe consolidation. A sputum sample is pending in the lab. What do you think is going on?

Answer 31

Atypical pneumonia due to increased susceptibility to infection as a result of anti-TNF biologics therapy.

Adalimumab is an anti-TNF monoclonal antibody. While it is effective at controlling RA, it does substantially increase the risk of susceptibility to infection, including by atypical organisms, but without the presentation of fever, and with a sudden onset. It also predisposes patients to disseminated TB if they are latently infected, and increased risk of skin cancer and lymphoma.

Question 32

Jack is an 8-year-old with ALL refractory to therapy. All treatment options that his doctors have tried have not been successful at inducing remission, including a bone marrow transplant. You are the helpful medical student who has just read a paper on CAR-T therapy, and you think it might be useful for Jack, since it has successfully cured other pediatric patients with refractory leukemia. Please explain to your attending how CAR-T therapy works, and what the risks of the treatment are.

Answer 32

CAR-T therapy uses chimeric antigen-receptor T cells. You create a chimeric antigen receptor with HIGH affinity to the cancer cells (essentially, a super high affinity TCR) and combine that with CD28 (costimulatory domain) and CD3 (signaling domain), and put that on the patient’s own T cells in the lab. When you reintroduce these T cells, they create a response to the cancer cells with T cell stimulation and costimulation at the same time! If the cells stay alive and proliferate, you can get a great response to the cancer. You can also potentially include a suicide gene to turn the cells off at the right time.

The risk of this therapy, of course, is the potential to induce a cytokine storm, which can be fatal if untreated. This can be treated with IL-6 inhibitors to help calm down the inflammatory reaction.

Question 33

A 34-year-old woman presents to clinic complaining of a painful lesion “in her vagina.” She is sexually active with her boyfriend of two years. Up until last month, they used condoms, but they are currently monogamous and she had an IUD placed about a month ago, so they have recently stopped using condoms. Neither she nor her partner have ever been tested for STIs. On exam you see ulceration of the labia that the patient reports is painful and itchy. It does not bleed.

Answer 33

HSV genital ulcer

HSV-1 lives latently in the trigeminal ganglia. HSV-2 lives latently in the sacral ganglia.

Subclinical shedding is the number one cause of transmission. Chances are, her partner has HSV (1 in 6 adults do) but was subclinically shedding the virus when they began having sex without a barrier, leading to her infection.

Diagnose with PCR. Can use IgG serology to assess past history of infection.

Counseling is a critical part of management - need to encourage patients to take suppressive therapy.

Tx: acyclovir or famcyclovir or valcyclovir. Treatment reduces viral load and reduces shedding but does not eliminate the disease.

Question 34

An 18-year-old male presents to student health because of a nodule on his arm. He says that he keeps trying to pop it, like the pimple-popping videos on YouTube, but despite successfully popping it last week, it has not gone away and has become more red and swollen. On exam, the 5mm in diameter nodule is domed, and has a punctum in the center. It expresses foul-smelling white drainage.

Answer 34

Epidermoid cyst

Although people colloquially call this a sebaceous cyst, it’s not actually sebaceous. This is caused by trapped epidermal cells, and leaves a pocket of macerated keratin (the white goo that squirts out).

Advise your patient not to squeeze it! Rupture leads to further inflammation and damage.

Tx: intralesional steroids or oral ABX to reduce inflammation. Excision will prevent recurrence, although you have to remove the entire wall of the cyst. Incision and drainage may reduce the size of the cyst temporarily.

Question 35

A 26-year-old woman in her first pregnancy prevents to your OB/GYN practice for prenatal care. On careful review of her history, you learn that she has had recurrent episodes of genital warts, although none in the past several years. She tells you that she has been told she has herpes, but she has never taken any medication for it. How do you counsel her?

Answer 35

Pregnant women with a history of HSV infection need to take acyclovir to suppress the infection starting at 36 weeks into the pregnancy. This is to prevent infection of the neonate, which could lead to sores and encephalitis

Question 36

Mrs. Small is a 70-year-old woman who presents for her annual physical. History and exam reveal mild lymphadenopathy. As part of your routine work-up, you order a CBC with differential. You get the results back the next day.

CBC results: 
WBC 20,000
Leuk 11,000
Hgb 14
HCT 39
PLT 250,000
CBC is significant for high numbers of small lymphocytes, with a few smudge cells. 

You order a LN biopsy which reveals large areas of small lymphocytes, staining positive for Bcl-2.

Answer 36

CLL/SLL

Lymphoid malignancy, indolent, chronic. Characterized by small lymphocytes with clumped chromatin that tend to smudge on smear. May present more like a leukemia or more like a lymphoma (leukemia > lymphoma).

LN architecture is not preserved. The neoplastic cells fill the LN in diffuse, cloud-like proliferation centers. There are no follicular DCs, and no normal GCs. Bcl-2 is turned on.

Most common adult leukemia in the Western world. Often asymptomatic on diagnosis, often found on routine labs, often with low tumor burden.

Can lead to symptoms - marrow failure, hemolytic anemia (extravascular hemolysis), splenomegaly, recurrent infection, autoimmune cytopenias, etc. This would be when you would treat; otherwise you just watch and wait.

Question 37

Your awesome friend who works for MSF is currently at a clinic in Africa, and texts you the following information while you are sitting at home playing video games over the weekend after an exam: “Just had report of pt with sudden high fever and tons of bleeding and vomiting, lethargic, becoming nonresponsive. Really sudden onset. Pt died. Don’t worry I haven’t been exposed but going to PPE training just in case there’s another one.” What advice should you give your friend?

Answer 37

Ebola virus

RNA virus covered in a lipid coat that causes hemorrhagic fever. The target organ is vascular endothelium, leading to end-organ damage, but the most severe damage is from the innate immune response. When the virus spreads to macrophages and DCs, it leads to tons of inflammatory mediators causing procoagulant activity, and release of tissue factor, causing DIC.

It can be spread person-to-person so complete PPE including a respirator, double gloves, everything covered with impermeable barriers, etc is necessary.

Zoonotic spread is key as well.

Hemorrhagic fevers tend to present with prodromal illness of high fever, malaise, headache, weakness, dizziness, myalgias, arthralgias, N/V/D. More specific prodromal symptoms include conjunctival injection (red eyes), pharyngitis, rash, edema, hypotension, shock, and bleeding from mucous membranes. WHO criteria for diagnosis is fever over 101 for less than 3 weeks, severe illness, no predisposition or alternative cause and 2+ hemorrhagic symptoms.

Ebola is characterized by a very rapid onset, sudden high fever and massive GI symptoms on day 10 with patient “prostrate,” and by day 11, ecchymosis, brain damage, and death.

Tx: supportive care - correct coagulopathies, avoid anti-platelet drugs and IM injections. Ribavirin prophylaxis is helpful in high-risk contacts.

Question 38

A 26-year-old woman presents to clinic because she is feeling generally unwell. She complains of fever, chills, and poor appetite. On exam you notice a rash with papules and pustules on her arms and legs, that also covers her palms and soles. She has a mostly sedentary lifestyle and does not frequently do activities in the outdoors. She works at a call center. She is sexually active. She has been on prednisone recently for reactive arthritis following infection with chlamydia.

Answer 38

Secondary syphilis

Wear gloves when examining this rash! Secondary syphilis typically presents with a maculopapular or pustular rash that characteristically involves palms and soles. Constitutional symptoms are present in 70% of patients.

If you see a rash of unknown etiology, consider syphilis!

Tx: penicillin! If allergic, desensitize the patient, and then give penicillin. If pregnant, give penicillin.

Question 39

A 4-year-old boy is brought into your clinic by his parents because “his butt itches a lot.” His parents also report that he has complained of stomach pain over the past few days and has been generally irritable, without much appetite.

Answer 39

Pinworm - enterobicus vermicularis

Most common helminthic infection in the US. Eggs are ingested, they mature in the intestine, and then release eggs in the stool. Often asymptomatic, but the most common symptom is perianal pruritus, especially in kids, leading to scratching. Anorexia, irritability, and abdominal pain also occur.

Dx: stool ova and parasite exam. Eggs look like a football with one side flatter than the other. Scotch tape test is also a good way to look at the eggs.

Tx: albendazole or mebendazole

Question 40

A 40-year-old man presents to clinic complaining of a penile lesion. On exam the lesion is a beefy red lesion with rolled edges. It is friable and bleeds easily. The patient says it does not hurt. His history is significant for recent travel to the tropics.

Answer 40

Donovanosis - klebsiella granulomatis.

This is a rare STD that is more commonly found in the tropics. Diagnosed by Donovan bodies in PMNs. Treat with azithromycin.

Question 41

A patient presents to your office with a pedunculated nodule on his finger. It is bright red and bleeds easily. How do you treat this and why?

Answer 41

This presentation is typical of a pyogenic granuloma (randomly overactive granulation tissue). However, similar findings could be observed in an ulcerated SCC, amelanotic melanoma, Kaposi Sarcoma, etc.

Consequently, shave and cauterize… And send tissue to pathology for biopsy, just to rule out malignancy!

Question 42

A 53-year-old woman presents to clinic for evaluation of a three-month history of joint pain in her wrists and fingers. She has a total of 13 swollen joints, many of which are her MCPs and PIPs. On physical exam the joints are swollen and warm to the touch, and appear slightly deformed. The deformities are nonreducible. She displays a positive Phalens sign. She has a 30-pack-year smoking history. You decide to order some labs and an X-ray of her hand. The XR displays erosions at her MCPs. She has an increased ESR and elevated CRP. RF and CCP are positive. ANA are negative.

Answer 42

Rheumatoid Arthritis

Inflammatory polyarthritis. Diagnosis requires synovitis without alternative cause, and then criteria include number of joints involved, RF and CCP low or high titer, elevated ESR and CRP, and history of symptoms >6 weeks.

Disease can also have systemic manifestations. Extra-articular disease is possible, including secondary Sjogren’s syndrome, and premature CAD is also possible.

Mild extra-articular manifestations: rheumatoid nodules; iron deficiency anemia; Raynaud’s; Sjogren syndrome

Severe extra-articular manifestations: ILD; scleritis; pericarditis or pleuritis; vasculitis

Smoking is a significant risk factor, as is HLA-DR B1 0401, and the two combined lead to a 30x higher risk.

Pathophysiology: TNF-alpha is central to the inflammatory cascade, and IL-1 and IL-6 also contribute to the inflammation. MMPs lead to the erosions.

Treatment: Initial management starts off with NSAIDS. However, remission is the goal, and DMARDs are the right drugs for that. Typical DMARD regimen is triple therapy - MTX (blocks purine synthesis by inhibiting DHFR), SSZ (antibiotic and anti-inflammatory), HCQ (antimalarial that stabilizes lysosome, and decreases antigen presentation, autoantibody production, and cell destruction).

If DMARDs don’t work, biologics may be a good option. Anti-TNF biologics block inflammation, but greatly increase risk of infection. These include infliximab, adalimumab, etanercept, etc. Other biologics include abatacept (CTLA-4 Ig - blocks Tc costimulation, and doesn’t carry as high an infection risk), rituximab (anti-CD20), tucilizumab (anti-IL6), etc.

Preventive care for these patients includes pregnancy planning and birth control, since MTX is teratogenic, CVD prevention, and avoidance of love vaccines. Patients probably need C-spine clearance for surgery.

Question 43

A 19-year-old premed arrives in your dermatology clinic in a panic. She just learned about melanoma in her cancer biology class, and is concerned that she is at risk for it because she has a few moles. She is of Caucasian race and very fair-skinned, with light blonde hair and numerous freckles on her face and arms. On skin exam, you notice about ten round, flat, small macules on her back and upper arms. They are uniform in shape and are all less than 5 mm in diameter. How do you counsel her?

Answer 43

These are normal manifestations of common melanocytic nevi.

These are formed from groups of clustered melanocytes. They tend to appear in childhood through the mid-30s. They start off at the junction between the epidermis and dermis, and appear flat and dark. Later in life, some drop into the dermis and manifest as lighter papules that are raised and maybe speckle. Fully dermal nevi are completely detached from the epidermis and appear pink and raised.

Treatment for this is reassurance that these are not cancerous. Patients should be counseled to use photoprotection. Nevi should be excised if they start changing, look atypical, get frequently traumatized, or are cosmetically distressing to the patient. The total number of common melanocytic nevi is indicative of melanoma risk, and with this patient’s fair skin she should be counseled to wear sunscreen and protective clothing to decrease her overall risk.

Question 44

A young couple brings their 1-week-old baby boy to your clinic for his first postnatal pediatrics visit. The baby appears lively and healthy. The parents’ only concern is a large dark area on his arm that has been there since his birth. On exam you observe a large, oval-shaped dark patch with some irregular coloration on the baby’s right upper arm, about 5 square centimeters in area, with coarse dark hairs.

Answer 44

This is a congenital nevus.

Classic presentation is described in this case. They are present from birth. There is an increased risk of malignancy with a giant congenital nevus (20 cm or greater or covering a whole segment of the body), so these may be excised. It is unclear whether excision of small and medium congenital nevi actually reduces malignancy risk.

Question 45

A 70-year-old man presents to your clinic for his yearly physical. While you are doing his HEENT exam, he points to his cheek and tells you that he noticed a rough spot there when shaving, but couldn’t really see it in the mirror. You can only barely see a lesion, faintly pink with fine scale, but when you run your finger over it, it feels gritty to the touch.

Answer 45

Actinic keratosis

Product of sun exposure - epidermal dysregulation and faster replication occur. This lesion is precancerous. Increased incidence in patients with fair skin, more sun exposure, age, males, prior history of these. While most won’t convert into SCC, be extra suspicious if they grow, become infuriated, persist after treatment, are ulcerated, or are on a mucosal membrane.

Tx: sunscreen for prevention. Some will resolve over time. Most people want them treated, so they can be frozen off with liquid nitrogen. Biopsy if they recur twice.

If there is a diffuse distribution of these, topical fluorouracil can be used as treatment. Patients get a rash from this, though - worse the greater the distribution of the lesions.

Question 46

A 55-year-old man presents to the ED with troublesome neurological symptoms. You diagnose him with a stroke. While examining him, you notice that his right pupil is small and irregular and does not react to light, although it does accommodate to near vision. In his chart, he has a 2-year history of tinnitus and vertigo. Incidentally, during his hospital stay, you find that he has an ascending aortic aneurysm.

Answer 46

Tertiary syphilis

Characterized by progressive neural and vascular dysfunction, 5-30 years after infection. This is due to the endarterial damage caused by the disease.

S/Sx include ascending aortic aneurysm, stroke, personality changes, vision changes, Argyll Robinson pupil (small, irregular, nonreactive to light, accommodates to near vision), tinnitus, vertigo, and granulomatous changes to mucocutaneous tissue and bone.

Tx: penicillin! If allergic, desensitize the patient, and then give penicillin. If pregnant, give penicillin.

Question 47

A 16-year-old boy presents to your clinic with eye pain and diminished vision in both eyes for the past week. He has a history of nearsightedness and wears reusable corrective contact lenses, which he keeps in a contact lens case. Last week he was away at summer camp, in a rural area with minimal bathroom facilities.

Answer 47

Acanthamoeba keratitis

Acanthamoeba can get onto contact lenses and cause this condition.

Question 48

You are an internal medicine doctor treating a patient over time for multiple issues. Recently he was treated for food poisoning following eating a dinner of roast turkey at a large catered event. You ended up diagnosing him with Salmonella infection. He recovered uneventfully. However, it’s been about two weeks, and now he sends you a message on MyChart complaining of pain in his left lower back and also in multiple other joints including his knees. He feels tired and stiff. When he comes in, his eyes are bloodshot and he is complaining of urinary symptoms as well. The joints in his toes are also swollen.

Answer 48

Reactive arthritis

80% are HLA-B27+. These patients frequently present with peripheral SpA or asymmetric axial SpA after a latency period following GI or GU infection (especially chlamydia, salmonella, yersinia, shigella, campylobacter).

Symptoms typically include arthritis, urethritis, conjunctivitis (“Can’t see, can’t pee, can’t climb a tree”). Derm manifestations include keratoderma blenorrhagicum on soles of feet, or circinate balanitis on the penis. Other findings may include calcaneal erosions, dactylitis (swelling of digits), and periostitis and erosions, which may manifest as fuzziness/fluffiness on XR.

Tx: NSAIDs, oral corticosteroids, can add topical corticosteroids for skin.

Question 49

Helene is a 30-year-old woman who you are treating for a new diagnosis of rheumatoid arthritis. Her PCP referred her to you with her disease managed by NSAIDs and low-dose prednisone. You would like to start her on triple therapy. What does that entail, and what counseling should you give her?

Answer 49

Triple therapy - methotrexate, sulfasalazine, hydroxychloroquine.

MTX inhibits dihydrofolate reductase, blocking purine synthesis. Its side effects include teratogenic effects, cirrhosis (especially with EtOH), mouth sores, GI symptoms, fatigue, and lung toxicity, as well as increased infection risk. For this drug, she should be counseled to watch her alcohol intake, and she needs to be on birth control and be certain that she is not pregnant. She’ll also need a baseline HepB/C screen and CXR, and routine evaluation of CBC, LFTs, and renal function. Leflunomide is similar to MTX in that it’s a pyrimidine/purine inhibitor, has similar side effects, and is monitored similarly.

Sulfasalazine is a sulfa antibiotic. It can cause GI upset and liver toxicity, but it’s safe in pregnancy or with alcohol. She should undergo a G6PD screen first, and should have routine CBC and LFTs drawn. Sulfa allergy is a contraindication.

Hydroxychloroquine is a mild antimalarial that stabilizes the lysosome, and decreases antigen presentation, autoantibody production, and cell destruction. It is associated with ocular toxicity and neuromyopathy. She should be monitored with visual field testing every 1-5 years.

Question 50

A 60-year-old woman presents to clinic for evaluation of a nodular lesion on her cheek that bleeds easily. The lesion is painless, and it has been there for a while, but recently seems to have gotten larger and has become more friable. On exam the nodule appears pearly and translucent, with a rolled border.

Answer 50

Basal cell carcinoma, nodular form

Most common cancer and most common skin cancer. 3 times more common than SCC in healthy patients (SCC is more common in immunosuppressed patients).

Pathogenesis: derived from basaloid cells.

Can also present as a superficial BCC (subtle erythematous patch that is slow-growing, friable, translucent, with a rolled border) or a morfeaform BCC (depressed scarlike hypopigmented papule with indistinct margins - most aggressive).

If low-risk excise with a 4mm margin. If high-risk, Mohs surgery. Increased risk of recurrence in the mask area of the face. Can be very locally destructive if untreated.

Question 51

You are traveling to the equatorial zone of the world on a trip with family and friends. Like a good medical student, you got all your required vaccines before the trip. One person in your group does not like shots, and avoided getting any vaccines. During your trip, that person gets sick. He develops a fever and muscle and joint aches. You notice that his eyes become very red, and he experiences vomiting, back pain, and jaundice. He asks you to examine him, given that you’re a medical student. You observe hepatosplenomegaly on exam.

Answer 51

Yellow Fever

RNA virus covered in a lipid coat that causes hemorrhagic fever. The target organ is vascular endothelium, leading to end-organ damage, but the most severe damage is from the innate immune response. When the virus spreads to macrophages and DCs, it leads to tons of inflammatory mediators causing procoagulant activity, and release of tissue factor, causing the potential for DIC.

Hemorrhagic fevers tend to present with prodromal illness of high fever, malaise, headache, weakness, dizziness, myalgias, arthralgias, N/V/D. More specific prodromal symptoms include conjunctival injection (red eyes), pharyngitis, rash, edema, hypotension, shock, and bleeding from mucous membranes. WHO criteria for diagnosis is fever over 101 for less than 3 weeks, severe illness, no predisposition or alternative cause and 2+ hemorrhagic symptoms.

This is the only hemorrhagic fever with a vaccine, which is actually very effective.

Tx: supportive care - correct coagulopathies, avoid anti-platelet drugs and IM injections. Ribavirin prophylaxis is helpful in high-risk contacts.

Question 52

A 26-year-old patient presents to your clinic to establish care with you serving as his PCP. He has not seen a doctor since high school other than for the occasional acute complaint. As you discuss his history, you find out that he’s been having bouts of abdominal pain and bloody diarrhea off and on for six months. He has lost weight over that time, and has also experienced unpredictable fecal urgency and fatigue. He has a prior history of joint pain in his knees and hips that has been going on chronically for about two years. On exam, his knees are swollen. There are tender, erythematous indurations on his calves bilaterally. You send him for colonoscopy, which reveals mucosal ulcerations continuously from the rectum up to the splenic flexure.

Answer 52

Ulcerative colitis with IBD-associated spondyloarthritis. This patient also has erythema nodosum.

IBD-associated SpA is most commonly peripheral but can be axial. Sacroileitis is usually symmetric. 30% of patients are HLA-B27+.

Tx for IBD-associated arthritis: avoid NSAIDs! They can worsen IBD, so use corticosteroids instead. TNF inhibitors can be used. Infliximab tends to work well, while etanercept has less activity in these patients.

Ulcerative colitis tends to manifest with bloody diarrhea, fecal urgency, tenesmus (rectal dry heaves), abdominal pain, fever, iron deficiency anemia, and weight loss. It is only mucosal inflammation, in the colon only, and starts at the rectum and moves proximally without skip lesions. It should be evaluated with colonoscopy and pathology for diagnosis. Pathology will show that only the mucosa is involved. It does increase the risk of colon cancer. PSC can also occur in these patients. While there’s no cure, therapy starts with 5-ASA meds (including SSZ and mesalamine). Corticosteroids can be used for induction of therapy. Immunomodulators (6-MP, MTX, azathioprine) that are steroid-sparing can be used for severe flares and maintenance therapy, although some patients cannot tolerate them. Biologics may also be used if other treatments do not work. Surgery can be curative for UC and is used for severe or refractory disease.

Question 53

A 50-year-old woman presents to clinic with ongoing upper respiratory symptoms that she says feel like pneumonia. She reports cough, dyspnea, and hemoptysis. She has also had stomach pain and vomiting, and thought she noticed something wiggling in her stool. You order a CBC and find that she is eosinophilic. You also perform a rectal exam to evaluate the complaint of “something wiggling,” and find a very long, yellowish worm that is smooth with no segmentation protruding from her rectum.

Answer 53

Ascaris infection

Largest nematode. 15-35 cm long, not segmented. The eggs are the infective life stage. Egg is ingested, goes to the intestine, molts, penetrates through the intestine, matures in the lungs and irritates bronchioles, patient coughs, the worm gets back into the gut that way and matures further, and then eggs are released in the stool.

Patient presented with Loeffler’s pneumonia symptoms. Differential for this plus eosinophilia is ascaris, hookworm, strongyloides.

Patients may also present with intestinal obstruction and biliary occlusion.

Dx: eggs are microscopic and found in the stool, or you can find the worm.

Tx: albendazole, mebendazole, pyrantel pamoate in pregnancy

Question 53

A patient comes in with an acutely red, swollen, and warm knee. He is 24 years old. He reports no trauma. A joint aspirate reveals purulent fluid with greater than 100,000 nucleated cells. The joint aspirate is sent for a gram stain and reveals gram-negative diplococci.

Answer 53

Septic joint from disseminated gonococcal infection.

Should be treated with ceftriaxone and either azithromycin or doxycycline.

Remember that acute monoarthritis is infection until proven otherwise! Joint aspiration should be performed to rule in or rule out infection.

Non-inflammatory: straw clear, viscous, less than 1500 nucleated cells.
Inflammatory: cloudy, thin, 1500-100,000 nucleated cells
Septic: purulent, >100,000 nucleated cells
Trauma: bloody

Question 55

A 39-year-old man presents to your clinic with lower back pain for the past six months. The pain is worst when he gets up in the morning, and improves with activity, but gets worse by lunchtime after he has been sitting at his desk for hours. He regularly takes naproxen for the pain, which helps immensely. His family history is significant for his mother, who has psoriasis, and his grandmother, who has some kind of joint disease. He seems hunched over in clinic. You have him stand with his back against the wall and you measure his occiput-wall distance, which is 2 cm. In addition, you perform a modified Schober’s test. The change that you observe is 3 cm.

Answer 55

Ankylosing spondylitis

More common in patients <45 years, slight predominance of male over female. HLA-B27 is found in most patients. Related family history includes ankylosing spondylitis, but also anterior uveitis, IBD, reactive arthritis, and psoriasis.

Disease usually starts in the sacroiliac joints, and then moves further up the spine. Early sacroileitis presents as widening of joints, and erosions. Late sacroileitis leads to fusion of the joints, as systemic inflammation moves up the spine over time. Marginal erosions are present, as are syndesmophytes, ossification of ligaments, and loss of bone density. This can lead to restrictive mobility, restrictive lung disease, and osteoporosis.

Other disease manifestations may include enthesitis (especially affecting the Achilles and calcaneus tendons), dactylitis (swelling of a digit), anterior uveitis (ciliary injection, pupil irregularity, etc which can lead to glaucoma and blindness), aortitis affecting all layers of the aorta, and transverse myelopathy (weak on the exam).

On exam, patients will often have kyphosis (increased occiput-wall distance) and changes <5cm on a modified Schober’s test.

Dx: positive evidence on XR or MRI plus one clinical feature OR HLA-B27+ and 2 clinical features.

Tx: 1st line therapy is NSAIDs. TNF inhibitors are used if NSAIDs fail or are contraindicated. For peripheral SpA, SSZ/MTX/leflunomide are used. Also, physical therapy improves mobility in SpA patients.

Question 56

A 30-year-old woman of Asian descent presents to clinic with nonspecific symptoms including fever, night sweats, joint pain, and muscle pain that have been going on for the past few weeks. When checking her in, the nurse notices that the patient has very weak radial pulses. On exam, you confirm this finding, and also note some discrepancy in the BP between her two arms on exam, as well as weak brachial pulses. You hear a bruit over her right carotid. What diagnostic test should you do, and what will that tell you?

Answer 56

Takayasu arteritis

Associated with younger (<40) females, especially of Asian descent. Classically presents with nonspecific constitutional symptoms, claudication, “pulselessness” - weak upper extremity pulses, arthritis, myalgias, BP discrepancies on exam, bruits.

Angiogram of the thoracic aorta is an important diagnostic test. This will reveal granulomatous thickening and narrowing of the aortic arch and proximal great vessels.

Labs will demonstrate elevated ESR but normal CBC.

Tx: corticosteroids

Question 57

An 80-year-old lady presents to clinic with a headache that localized to her right temple, and occasional bouts of jaw pain when she has been eating or speaking. She also has constitutional symptoms such as a fever and fatigue. She has also noticed some vision changes. On exam you note a temporal bruit, scalp tenderness, and ischemic retinopathy. You order labs and observe that she is anemic, with elevated platelets and an ESR of 54. What do you think is going on, how will you manage it, and what other condition do you expect that you might find?

Answer 57

Giant cell arteritis

Most commonly in adults over 50, F>M.

Pathophysiology characterized by focal granulomatous inflammation affecting branches of the carotid artery. Presents with unilateral headache (from the temporal artery), jaw claudication, ischemic retinopathy from occlusion of the ophthalmic artery that can lead to blindness. Labs can include anemia, thrombocytes is, and elevated ESR.

Tx: immediate treatment with high-dose corticosteroids, in order to prevent blindness. Do this IMMEDIATELY before anything else. You can then do a temporal artery biopsy to show the granulomatous inflammation. Skip lesions are typical on the biopsy.

Associated with polymyalgia rheumatica - systemic limb girdle pain and stiffness, without muscle weakness. Will show joint inflammation and decreased range of motion of shoulders and hips, with elevated ESR and CRP, and sometimes elevated LFTs.

Question 58

John is a 30-year-old man who presents to clinic today with symptoms of fever, weight loss, malaise, headache, and abdominal pain. On exam you note that he has wrist drop and foot drop, some purpura on his limbs, and hypertension. He is HepB seropositive. You order some labs, including a urinalysis, and find that his creatinine is elevated and that he has proteinuria. C-ANCA and P-ANCA come back negative. What is going on, what is the pathology, and how do you manage his condition?

Answer 58

HepB-associated Polyarteritis Nodosa

HepB is associated with about 30% of cases of polyarteritis nodosa. The renal findings in this case have two causes. HepB causes membranous glomerulonephropathy, while PAN causes necrotizing arteritis of renal arterioles. The disease is immune complex mediated. Pulmonary arteries typically are not involved. Pathology will reveal transmural inflammation of the arterial wall with necrosis. This leads to tissue ischemia and infarction, aneurysm, and bleeding.

On arteriography, there will be renal microaneurysms. Abdominal arteriography should be done.

Presents with constitutional symptoms, abdominal pain, maybe melena, hypertension, wrist drop/foot drop, purpura, livedo reticularis, and renal damage.

Labs: no ANA, normal complement, cryoglobulins negative.

Tx: corticosteroids and antivirals since this is HepB-associated. Avoid steroid-sparing immunosuppression in these patients.

Question 59

41-year-old woman presents to clinic with a net-like rash on her legs that appears when she is cold. She is also complaining of abdominal pain, fever, and malaise. On exam you see pronounced wrist and foot drop, and note that she is hypertensive. She has no family history or PMH of note. Her labs reveal normal complement, no evidence of cryoglobulins, and no ANA. UA reveals proteinuria. Her creatinine is elevated.

Answer 59

Polyarteritis Nodosa

The disease is immune complex mediated. Pulmonary arteries typically are not involved. Pathology will reveal transmural inflammation of the arterial wall with necrosis. This leads to tissue ischemia and infarction, aneurysm, and bleeding. 30% of cases are associated with HepB, but this case is idiopathic.

On arteriography, there will be renal microaneurysms. Abdominal arteriography should be done.

Presents with constitutional symptoms, abdominal pain, maybe melena, hypertension, wrist drop/foot drop, purpura, livedo reticularis, and renal damage.

Labs: no ANA, normal complement, cryoglobulins negative.

Tx: corticosteroids and cyclophosphamide

Question 60

A young father brings his 3-year-old daughter to your family medicine clinic because of concerning symptoms for five days. The father tells you that the girl has been running a fever, and has had a rash for a day or two that has recently started peeling. On exam, you note that her lips are red and cracked, and her tongue is shiny and red with some dimpling of the taste buds. Her conjunctiva are red and swollen. She has a rash that is peeling, with sheets of skin coming off her hands and feet. She also has edema and erythema on her hands and feet. You also notice that she has unilateral cervical lymphadenopathy, with one particularly swollen node measuring 2 cm. She is irritable and tries to move away from the light when you examine her eyes. She is very tachycardic. What is your diagnosis, and how do you manage her?

Answer 60

Kawasaki Disease

Classic presentation is young children under five, but can present in other age groups (although older children may have an incomplete presentation). Pathology is that the acute phase causes damage to vessel walls, leaving to aneurysms and MI.

5 criteria for diagnosis - must have a fever for 5 days plus 4/5 of the following: bilateral no purulent conjunctivitis w/ limbic sparing; mucosal changes like a strawberry tongue and swollen cracked lips; unilateral cervical LAD greater than 1.5 cm,; polymorphous rash; extremity changes including edema, erythema, peeling. Patient may be irritable and light-sensitive (aseptic meningitis) and/or may have myocarditis (evidenced by being tachycardic out of proportion to the fever). If untreated, this can lead to MI. It also causes aneurysms in coronary arteries, and can predispose to MI after the disease is acutely over, but early in life.

Work up should include echocardiogram. Patients should receive screening echoes after recovery to check for coronary aneurysms. This is the most common cause of pediatric MI.

Tx: IVIG and aspirin! In a 10-day window, IVIG reduces aneurysm risk from 25% to 5%. Give high-dose aspirin acutely and low-dose aspirin later to prevent clotting.

Question 61

A 50-year-old man presents to your clinic because he is itchy after he takes a shower. He reports that he has lost substantial amounts of weight recently. His PMH is significant for an MI six months ago and for gout in his right knee for which he is currently taking colchicine. He has a reddish complexion, although you notice no rash. On exam, you note that the spleen is palpable 6 cm below the left costal margin. You order a CBC with differential and a few other labs. HCT is 56, but EPO levels are low/normal.

Answer 61

Polycythemia Vera

Most have a JAK2 mutation, leading to copious RBC production. Low/normal EPO distinguishes PV from secondary polycythemia, which has high EPO.

Clinical features are symptoms resulting from increased viscosity, hypervolemia, and hyperactive metabolism: thrombotic disease, splenomegaly, reddish complexion, pruritus from histamine release after bathing, weight loss, gout. Extramedullary hematopoeisis leads to the splenomegaly. This may evolve to primary myelofibrosis or AML.

Tx: lower the hematocrit below 45 with phlebotomy and/or hydroxyurea. Aspirin may help prevent thrombosis, and hydroxyurea can help lower PLT count. Median survival is 10-15 years.