Human immunodeficiency virus (HIV) is a retrovirus that infects primarily CD4⁺ T helper cells. The subsequent depletion of these cells, vital to immunologic competence, causes decreased protection against opportunistic infections.

• AIDS: when the CD4⁺ T cell counts fall below 200 cells/mm³ or opportunistic infections occur.

Among HIV-infected men in all age groups, 68% identified their risk behavior as men having sex with men, 13% reported a history of injection drug use, and 11% reported heterosexual contact as their route of HIV exposure.

Of HIV-infected women, 71% identified heterosexual sex as their HIV exposure, and 27% had IV drug use.

• 50% to 90% of new HIV seroconversions are associated with an acute or primary HIV infection ( also called an acute retroviral syndrome).

Presentation:

• The onset of illness is 2 to 6 weeks after infection and correlates with peak viremia (> 1 million viral copies/mL).

Symptoms include:

1. fever
2. rash (erythematous maculopapular lesions on the face and trunk)
3. lymphadenopathy
4. nonexudative pharyngitis
5. Headache
6. myalgia
7. gastrointestinal symptoms
8. oral or genital ulcers

Laboratory:

1. Leukopenia
2. thrombocytopenia
3. elevated transaminase levels

Work up & Management

CD4 Count

The CD4 T-cell count (CD4 count) serves as the major laboratory indicator of immune function in patients
who have HIV infection. It is one of the key factors in determining both the urgency of antiretroviral therapy
(ART) initiation and the need for prophylaxis for opportunistic infections.

• ART (antiretroviral therapy) is now recommended for all HIV-infected patients.

In untreated patients, CD4 counts should be monitored every 3 to 6 months to determine the urgency of ART initiation. In patients on ART, the CD4 count is used to assess the immunologic response to ART and the need for initiation or discontinuation of prophylaxis for opportunistic infections.

Factors that affect absolute CD4 count.

The absolute CD4 count is a calculated value based on the total WBC and the percentages of total and CD4 count. This absolute number may fluctuate, or may be influenced by, factors that may affect the total WBC count and
lymphocyte percentages, such as use of bone marrow-suppressive medications or the presence of acute
infections.

Splenectomy may cause misleadingly high absolute CD4 counts.

Alpha-interferon, on the other hand, may reduce the absolute CD4 count.

Plasma HIV-1 RNA (viral load) should be measured in all HIV-infected patients at baseline and on a
regular basis thereafter, especially in patients who are on treatment, because viral load is the most important
indicator of response to antiretroviral therapy.

• A decrease in plasma viremia is associated with an improved clinical outcome. Thus, viral load testing serves as a surrogate marker for treatment response.

Optimal viral suppression is generally defined as a viral load persistently below the level of detection (<20 to
75 copies/mL). However, isolated increases (viral loads transiently detectable at low levels, typically <400 copies/mL) are not uncommon in successfully treated patients and are not thought to represent viral replication or to predict virologic failure.

Randomized controlled trials in patients with CD4 counts <200 cells/mm3 and/or a history of an AIDS-defining condition provide strong evidence that ART improves survival and delays disease progression in these patients.

HIV & Liver Disease

HIV infection is associated with more rapid progression of viral hepatitis-related liver disease, including cirrhosis, end-stage liver disease, hepatocellular carcinoma, and fatal hepatic failure. The pathogenesis of accelerated liver disease in HIV-infected patients has not been fully elucidated, but HIV-related immunodeficiency and a direct interaction between HIV and hepatic stellate and Kupffer cells have been implicated.

~~~ART in Liver Disease:

After controlling for level of liver and HIV disease stage, HCV co-infected patients receiving ART were approximately 66% less likely to experience end-stage liver disease, hepatocellular carcinoma, and fatal hepatic failure than patients not receiving ART.

HIV & Cardiovascular disease

HIV-infected persons are at greater risk for CVD events than age-matched uninfected individuals.

Persons living with HIV infection also have higher rates of established CVD risk factors, particularly smoking and dyslipidemia than HIV-uninfected individuals.

HIV & Malignancies

The incidence of several malignancies (particularly liver, anal, oropharyngeal, and lung cancers, Hodgkin lymphoma, and melanoma) is higher in HIV-infected subjects than in matched HIVuninfected controls, and the burden of these non-AIDS defining malignancies has continued to increase.

HIV & Neurological diseases

Effective viral suppression resulting from ART has dramatically reduced the incidence of HIV-associated dementia and severe CNS opportunistic infections.  Suppressive ART usually reduces CSF HIV RNA to undetectable levels.

HIV & Prevention of sexual transmission

Recent study results provide strong support for the premise that treatment of the HIV-infected individuals can significantly reduce sexual transmission of HIV. Lower plasma HIV RNA levels are associated with decreases in the concentration of the virus in genital secretions. Studies of HIV-serodiscordant heterosexual couples have demonstrated a relationship between level of plasma viremia and risk of transmission of HIV: when plasma HIV RNA levels are lower, transmission events are less common.

Lung cancer is the leading cause of cancer death in BOTH men and women.

Risk factors include:

~Smoking

~Asbestos

~COPD

~Exposure to heavy metals & gases

~Secondary smoke

Non-Small Cell Lung Cancer

• Non-small cell lung cancer accounts for 85% of all lung cancers.

Non-small cell lung cancer is divided further into:

1. adenocarcinoma
2. squamous cell carcinoma
3. large cell carcinoma

Staging is essential in guiding the therapeutic decision-making process, all patients must be staged!

At diagnosis, 20% have localized disease, 25% have regional metastasis, and 55% of patients have distant spread.

Presentation:

~Cough
~Chest pain
~SOB
~Hemoptysis
~Wheezing
~Hoarseness
~Recurrent bronchitis or pneumonia
~Weight loss and anorexia
~Fatigue & Malaise

The suspected diagnosis is usually seen on chest x-ray, and confirmed/staged with CT.  In addition, bronchoscopy, sputum cytology, mediastinoscopy, thoracentesis, thoracoscopy, and transthoracic needle biopsy play a role is initial diagnostic staging.

Treatment:

Surgery, chemotherapy, and radiation are the main treatment options.

Surgery is the treatment of choice for stage I and stage II non-small cell including lobectomy, wedge resection, or even pneumonectomy.

Small cell lung cancer (formerly known as oat cell carcinoma) is considered separately from non-small cell lung cancers  because of both their clinical and biologic idiosyncrasies. Small cell lung cancer is referrred to as a neuroendocrine carcinoma, and any questions presented on the boards will likely stress the paraneoplastic activity on a tumor.

If  you get a question where you are just lost, think of a paraneoplastic syndrome. . . all you need is the smoking history!

Overall in terms of treatment, its important to know that surgical resection could be curative for early disease (non-small cell).  Non-small cell and small cell treatments differ (thus the classification).

Patients with small cell lung cancer should receive 4-6 cycles of cisplatin or carboplatin based chemotherapy, but because there is so much activity in this field, knowing the specifics of treatment would be beyond what we need to know for the ABIM so don’t spend a lot of time on chemotherapies.

For lung cancers, the key is to:

• recognize a paraneoplastic syndrome
• recognize the vague presentations that lung cancer’s manifest
• recognize the initial steps in the work up

Look for the following characteristics in the history:

• A family history of essential tremor
• Tremor usually begins in one upper extremity and soon affects the other
• In 30% of cases, tremor involves the head followed by the voice, jaw, and face
• The tremor is absent while sleeping
• Alcohol helps the symptoms.

Caused by Legionella pneumophila

Symptoms

• Fever greater than 40 ^º C (>102 º F) with chills
• Cough (Dry or productive)
• Pleuritic chest pain
• Mental status changes with headache
• Diarrhea (watery) with nausea, vomiting, and/or abdominal pain
• Myalgias & arthralgias

Physical Exam

• Bradycardia (look for this . . . with fever, tachypnea, and change in mental status, they should be tachycardic!
• Tachypnea
• Localized rales

Labs

• Elevated LFT’s
• Elevated ESR
• Elevated ferritin levels
• Elevated C-reactive protein levels
• Hypophosphatemia
• Microscopic hematuria
• Proteinuria (40%)

Diagnosis

X-ray that shows patchy infiltrates consistent with atypical pneumonia. Direct fluorescent antibody staining (DFA), or the immunofluorescent antibody (IFA), and enzyme-linked immunosorbent assay (ELISA) will confirm the diagnosis.

Treatment

Azithromycin, doxycycline, or ciprofloxicin can all treat readily.

Vaccinations

• The hepatitis A and B vaccine is safe.
• The inactivated Flu vaccine is safe, and the live attenuated in contra-indicated (makes sense. . . right?)
• Polio is approved
• Tetanus / Diphtheria is okay if indicated
• HPV, MMR, Varicella, and Zoster vaccines are contraindicated
• The pneumococcal vaccines have inadequate data to determine (so you won’t be asked)

 Other Cardiac Concerns:

• Pregnancy may unmask occult mitral stenosis and these patients present with pulmonary edema and/or atrial fibrillation. They can be treated with digoxin, and while we’re on that topic. . .
• Cardioversion, procainamide, and verapamil are also okay during pregnancy.
• Contraindications to pregnancy include: primary pulmonary hypertension, dilated cardiomyopathy, Eisenmenger syndrome, and Marfan syndrome with dilated aortic root

Endocrine Issues

Presentation

Symptoms may include joint pain, stiffness (< 30 min), locking, and sometimes an effusion.

There are classic physical signs that are pathognomonic for OA.

• Heberden nodes (palpable osteophytes in the DIP joints) below:

• Bouchard nodes (effecting the PIP)

Remember that RA effects the MCP (MTP) joints while OA effects the DIP joints! Don’t get these confused. 

Osteoarthritis is typically diagnosed on the basis of clinical and radiographic evidence, in other words you need pain in the joint and radiographic evidence of osteophytes (if no radiographic evidence, then crepitus and/or morning stiffness can be substituted).

Treatment

The treatment approach should progress from non-pharmacologic to pharmacologic, non-invasive to invasive. Remember to encourage weight loss, exercise, physical therapy. . . then progress to topical medications, then acetaminophen and NSAIDS, etc.

The classic clinical presentation of Boerhaave syndrome usually consists of repeated episodes of retching and vomiting, typically in a middle-aged man with recent excessive dietary and alcohol intake.
These repeated episodes of retching and vomiting are followed by a sudden onset of severe chest pain in the lower thorax and the upper abdomen. The pain may radiate to the back or to the left shoulder. Swallowing often aggravates the pain.

Typically, hematemesis is not seen after esophageal rupture (helps distinguish it from a Mallory-Weiss tear).

Swallowing may cause coughing (communication between the esophagus and the pleural cavity).
effusion.

Many patients present with a pleural effusion.

Work-up

Chest radiograph will naturally be the first study and it may show pleural effusion, mediastinal widening, or signs of “air” where it shouldn’t be. 90% of chest films are abnormal!

Thoracentesis with examination of the pleural fluid can aid in diagnosis (undigested food particles and gastric juices usually are found).

• Esophagram should be ordered with gastrografin (NOT Barium). It typically shows extravasation of contrast into the pleural cavity.
• Endoscopy is not commonly used in this diagnosis.

A CT scan may be helpful if the patient is too sick for the swallowing study.

Treatment:

• Intravenous fluids.
• Antibiotics
• Nasogastric suction should be applied.
• Surgical consult ASAP. There are mortality data based on time from rupture with odds showing 70% survival within the first 12 hours, and dropping to 50% after 24 hours, and 90% after 48 hours.

This is CLASSIC board material! They would NOT want a board certified physician to miss this question. High mortality if diagnostically missed or muffed.

LOOK for this QUESTION!

It will be there!

Overview

• Hypomagnesemia is most often associated with hypokalemia (due to urinary potassium wasting) and hypocalcemia (due both to lower parathyroid hormone secretion and end-organ resistance to its effect).
• 30% of hospitalized alcoholic patients have low magnesium due to poor dietary intake, and alcohol’s interference with tubular absorption /re-absorption of magnesium

But in office-based questions, patients may present with:

Neuromuscular manifestations:

• Muscular weakness
• Tremors
• Seizure
• Paresthesias
• Tetany
• Positive Chvostek sign and Trousseau sign
• Vertical and horizontal nystagmus

Cardiovascular manifestations:

• Nonspecific T-wave changes – U waves
• Prolonged QT and QU interval
• Repolarization alternans
• Premature ventricular contractions – Monomorphic ventricular tachycardia
• Torsade de pointes
• Ventricular fibrillation
• Enhanced digitalis toxicity

Metabolic manifestations:

• Hypokalemia: will not correct, until the magnesium is replaced
• Hypocalcemia: a phenomenon largely explained by inhibition of parathyroid hormone bioactivity. Hypocalcemia will not resolve until the magnesium deficiency has been corrected.

Treatment: