Immunology Update: Biologics.

Biologics are substances made from a living organism or its products. These include genes, proteins (eg, antibodies, receptors, enzymes, inhibitors), recombinant proteins, and fusion proteins. Biologics often are produced using recombinant DNA technology. For example, monoclonal antibodies are produced by inserting human genes into immortalized cell cultures, which then produce the gene product (ie, an antibody) in large quantity. Another approach is to fuse genetic material from nonhuman sources (eg, mice) with human genetic material. The fused gene is inserted into a tissue culture that produces the gene product (ie, a chimeric monoclonal antibody). Biologics are used to manage many conditions, including malignant and nonmalignant conditions. They are widely used in the treatment of human epidermal growth factor receptor 2 (ERBB2 [formerly HER2 or HER2/neu])-positive breast cancer. They also are used in the treatment of leukemias, lymphomas, and colorectal and lung cancer. Biologics improve outcomes in autoimmune disorders, such as rheumatoid arthritis, ankylosing spondylitis, psoriasis, inflammatory bowel disease, and multiple sclerosis. Other uses include erythropoietin for renal failure-associated anemia and the new proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for treatment of patients with persistently elevated low-density lipoprotein levels despite statin treatment who are at high risk of cardiovascular events.

Immunology Update: Long-Term Care of Solid Organ Transplant Recipients.

Nearly 31,000 US patients received solid organ transplants in 2015 and the number is increasing. Care of transplant recipients includes management of a variety of common posttransplantation issues. Skin cancers are common because of immunosuppression and require skin examinations at intervals. Patients should be educated about the need to report new skin lesions. The rates of other cancers also are increased, including cancers of the head and neck, lung, esophagus, cervix, and urinary tract. Osteoporosis is common in transplant recipients; monitoring and early therapy are important. Patients should not smoke, and vaccinations should be current except for live-virus vaccines, which are contraindicated in patients with immunosuppression. Family physicians should be familiar with the posttransplantation immunosuppression drugs their patients are taking and know their adverse effects and drug interactions. For example, calcineurin inhibitors (eg, cyclosporine, tacrolimus) can impair renal function and increase rates of hypertension and myocardial ischemia. They also interact with statins, macrolide antibiotics, diltiazem, and other drugs. Interval laboratory testing is required to monitor the health of the transplanted organ (eg, renal function tests for kidney transplants, transaminases for liver transplants). Finally, clinicians should remain alert for development of opportunistic infection.

Immunology Update: Primary Immunodeficiency Diseases.

There are 264 primary immunodeficiencies (PIDs), most of which are rare. They are caused by complement deficiencies, defects in phagocyte function, impaired T-cell function, and/or impaired B-cell function with antibody deficiencies. Most patients with PIDs will present, at varying ages, with frequent infections. These infections can be common respiratory tract infections such as otitis media or pneumonia, or they can be unusual bacterial, fungal, or parasitic infections. Neonatal screening for severe combined immunodeficiency syndrome, one of the most common and serious PIDs, is now performed in most US states, but many PIDs manifest and are detected after birth. Clinicians should be alert for PIDs when patients have unusual or frequent infection and perform a diagnostic evaluation. After ruling out HIV and hepatitis C infection, the next step is to obtain a complete blood count, immunodeficiency panel, and immunoglobulin and complement levels. If results are abnormal, or if a PID is suspected clinically but the diagnosis is not clear, prompt referral to an appropriate subspecialist is indicated. Some PIDs can be managed with stem cell transplantation, and transplantation before the first serious infection is associated with better outcomes. In addition, antimicrobial prophylaxis is indicated for many PIDs patients to prevent opportunistic infections.

Immunology Update: New Vaccines.

A new 9-valent human papillomavirus (HPV) vaccine is effective against more cancer-causing HPV types than previous vaccines. HPV vaccine series started with previous vaccines can be completed with the 9-valent vaccine. Two new influenza vaccines are available for adults 65 years and older: a high-dose vaccine and an enhanced adjuvant vaccine. These elicit stronger antibody responses than standard-dose vaccines. Current guidelines specify no preference for the new versus standard-dose vaccines. Two new group B meningococcal vaccines are intended for use during outbreaks and for patients with asplenia, complement deficiencies, frequent occupational meningococcus exposure, or for patients who desire protection from type B meningococcus. These are not substitutes for the quadrivalent vaccine already in use. For pneumococcus, new recommendations state that 13-valent pneumococcal conjugate vaccine (PCV13) should be administered to patients 65 years and older, followed at least 1 year later by the polyvalent pneumococcal polysaccharide vaccine (PPSV23). For patients ages 19 to 64 years with immunocompromise and not previously vaccinated against pneumococcus, administration of these two vaccines should be separated by at least 8 weeks. Rotavirus vaccine is standard for infants at age 2 months. Also, there is a new cholera vaccine approved for use in the United States.

Cirrhosis: diagnosis, management, and prevention.

Cirrhosis is the 12th leading cause of death in the United States. It accounted for 29,165 deaths in 2007, with a mortality rate of 9.7 per 100,000 persons. Alcohol abuse and viral hepatitis are the most common causes of cirrhosis, although nonalcoholic fatty liver disease is emerging as an increasingly important cause. Primary care physicians share responsibility with specialists in managing the most common complications of the disease, screening for hepatocellular carcinoma, and preparing patients for referral to a transplant center. Patients with cirrhosis should be screened for hepatocellular carcinoma with imaging studies every six to 12 months. Causes of hepatic encephalopathy include constipation, infection, gastrointestinal bleeding, certain medications, electrolyte imbalances, and noncompliance with medical therapy. These should be sought and managed before instituting the use of lactulose or rifaximin, which is aimed at reducing serum ammonia levels. Ascites should be treated initially with salt restriction and diuresis. Patients with acute episodes of gastrointestinal bleeding should be monitored in an intensive care unit, and should have endoscopy performed within 24 hours. Physicians should also be vigilant for spontaneous bacterial peritonitis. Treating alcohol abuse, screening for viral hepatitis, and controlling risk factors for nonalcoholic fatty liver disease are mechanisms by which the primary care physician can reduce the incidence of cirrhosis.