Watch the Latest NEJM Quick Takes

Posted by Karen Buckley • March 18th, 2015

There may be important new progress in the treatment of Crohn’s Disease. Watch the 1-minute Quick Take video summary of the phase 2 trial of Mongersen, an oligonucleotide that interferes with a signaling pathway involved in the pathogenesis of Crohn’s Disease. Also, read the full article and editorial.

Watch other recent video summaries, including:

CABG vs PCI w/Everolimus-eluting Stents

Improved Air Quality and Lung Development in Children

Peanut Consumption in Infants at Risk of Peanut Allergy

Mass Treatment with Single-Dose Azithromycin for Yaws  

You may also wish to browse all previous NEJM Quick Takes.

CABG or PCI in Patients with Coronary Disease?

Posted by Chana Sacks • March 16th, 2015

The great singer Whitney Houston posed a question over 25 years ago that many still ponder today.  “Where,” she asked, “do broken hearts go?”

Of course, her classic song asks us to imagine a destination for the pain wrought by the dissolution of love.  Physicians, however, have more concrete possibilities in mind when asking where to take the hurting center of our emotional and physiologic lives: the cardiac catheterization lab versus the operating room. That is, for patients with multi-vessel coronary artery disease (CAD) who require revascularization, should first-line treatment be PCI or CABG?

Current guidelines suggest that CABG is the revascularization strategy of choice, but the studies that formed the basis for those recommendations compared CABG to PCI using first-generation stents.  The development of second-generation stents has renewed the debate about whether PCI might be just as effective as surgery.

Two studies, now published in NEJM, seek to answer this question.  The data from both suggest that while the answer is complicated, CABG seems to maintain its edge when it comes to long-term cardiovascular outcomes.

The first study is a prospective trial conducted in 27 sites in Asia.  Designed to enroll 1800 adults with angiographically confirmed multi-vessel CAD who were deemed to be candidates for either intervention, the trial ultimately included only 880 participants due to slow enrollment.  Participants were randomly assigned to PCI with everolimus-eluting stents or to CABG.  Patients with clinically-significant left main disease were excluded from the trial.

The second study, an observational registry analysis, used similar criteria to define multi-vessel CAD.  The investigators analyzed 18,000 patients included in a New York state database to compare outcomes between patients who had received everolimus-eluting stents and those who underwent CABG.

In the trial done in Asia, at a median follow-up of 4.6 years, the composite endpoint of death, MI, or target vessel revascularization occurred in 15.3% of patients in the PCI group versus 10.6% in the CABG arm (P = 0.04). There were no significant between-group differences in death or stroke, but there were significantly more spontaneous MIs and repeat revascularizations in the PCI arm.

In the New York registry study, at a mean follow-up of 2.9 years, the PCI group, as compared with CABG, had a higher risk of MI (1.9% per year vs 1.1% P<0.001) and repeat revascularization (7.2% per year vs 3.1% P<0.001), but PCI was associated with a lower risk of stroke (0.7% per year vs 1% P<0.001). As in the Asian trial, there was no significant difference in mortality between groups.
In an accompanying editorial, Stanford cardiologist Dr. Robert Harrington describes the limitations of an undersized randomized trial and the possible confounding inherent to an observational registry study.  He concludes, “To the extent that the data from these two studies can be relied on, there are clearly trade-offs between the two revascularization strategies that need to be discussed with patients as part of the shared decision-making process. The early hazard of CABG (the risk of stroke) may be unacceptable to some patients, whereas others might want to avoid the later hazards of PCI (the risk of needing a repeat PCI procedure or having a myocardial infarction).”

NEJM Deputy Editor John Jarcho agrees, noting that together these studies “offer physicians new data to help weigh the benefits of improved long-term cardiovascular outcomes associated with CABG against the possible harms of undergoing major surgery.”  These studies, then, offer some new knowledge and still leave the door open for continued debate about the best way to help patients (and their hearts) to find their way home.


Posted by Carla Rothaus • March 13th, 2015

In the latest Clinical Therapeutics review, a 67-year-old woman with osteoarthritis of the right knee seeks guidance regarding the possible benefit of hyaluronate injection. Injections of hyaluronate for viscosupplementation have been used in osteoarthritis of the knee, but their efficacy remains uncertain.

Recent estimates suggest that knee osteoarthritis affects approximately 250 million people worldwide. Typically, knee pain limits activity and impairs quality of life. The risk of mobility disability (defined as the need for help with walking or climbing stairs) attributable to knee osteoarthritis alone is greater than that associated with any other medical condition in people 65 years of age or older.

Clinical Pearls

- What is the rationale for treating osteoarthritis of the knee with intraarticular injections of hyaluronic acid (viscosupplementation)?

Hyaluronate is a naturally occurring component of the cartilage and the synovial fluid. Within the normal adult knee, there is approximately 2 ml of synovial fluid, with a hyaluronate concentration of 2.5 to 4.0 mg per milliliter. Hyaluronate is responsible for the rheologic properties of synovial fluid, enabling it to act as a lubricant or shock absorber, depending on the forces exerted on it. In osteoarthritis, synovial hyaluronate is depolymerized and cleared at higher rates than normal. These changes reduce the viscoelasticity of the synovial fluid. The therapeutic goal of administration of intraarticular hyaluronate is to provide and maintain intraarticular lubrication, which increases the viscoelastic properties of synovial fluid; this form of therapy is therefore sometimes termed “viscosupplementation.”

- Is there evidence that viscosupplementation is effective for osteoarthritis of the knee?

Despite numerous trials and meta-analyses, the efficacy of hyaluronate-related agents in patients with knee osteoarthritis remains debated and uncertain. Meta-analyses assessing the efficacy of this form of therapy have had discordant findings, possibly because each review used different search strategies and selection criteria to identify trials for inclusion in the analysis. There is also controversy over whether the molecular mass of hyaluronate influences efficacy. The effectiveness of intraarticular hyaluronate is at best modest and at worst, in some of the aforementioned meta-analyses, indistinguishable from that of placebo. Although there are some data suggesting that younger patients and patients with less-severe disease may have greater benefit from this treatment than do older patients and those with more advanced disease, further evidence is required to support this claim. The effect of intraarticular hyaluronate on the structural progression of osteoarthritis, especially after repeat administration over longer intervals, remains an open question, with some pilot evidence suggesting positive effects.

Morning Report Questions

Q: What side effects are associated with the procedure?

A: Minor side effects include pain at the injection site (which occurs in 1 to 33% of patients), local joint pain and swelling (in <1 to 30%), and local skin reactions (in 3 to 21%). More serious side effects can occur. Pseudoseptic reactions (occurring in 1 to 3% of patients), which are characterized by inflammation and swelling of the joint that are not caused by infection, can be severe and may require further medical treatment. These reactions usually occur after sensitization with the second or third injection of a series or with a repeat treatment course. True joint infections have also been reported, but these appear to be rare.

Q: What are the formal guidelines regarding viscosupplementation for treatment of osteoarthritis of the knee?

A: Consistent with the contradictory meta-analyses, available guidelines also have conflicting recommendations, despite being based on the same research evidence. A recent update of the evidence from the OARSI [Osteoarthritis Research Society International] suggested that the data from the more rigorous trials did not show a significant difference between the effect of hyaluronate and that of placebo; as a result, it was not recommended for the treatment of either knee or multiple-joint osteoarthritis. In the American Academy of Orthopaedic Surgeons clinical practice guideline, it was determined that the evidence was inconclusive and a recommendation could not be made for or against the use of intraarticular hyaluronate. Similarly, the 2012 American College of Rheumatology recommendations do not advocate the use of intraarticular hyaluronate for the initial management of knee osteoarthritis. However, if a patient does not have a satisfactory response to acetaminophen or nonsteroidal antiinflammatory drugs (NSAIDs), then the use of tramadol, duloxetine, or intraarticular hyaluronate is conditionally recommended.

A Man with Multiple Myeloma and Skin Tightness

Posted by Carla Rothaus • March 13th, 2015

In the latest Case Record of the Massachusetts General Hospital, a 68-year-old man was seen in the rheumatology clinic because of increasing skin tightness, joint pain, and edema of the hands and feet. Nine months earlier, he had received a diagnosis of multiple myeloma and had undergone autologous stem-cell transplantation.

Fibrosing dermopathies are a group of diseases with overlapping clinicopathological features.

Clinical Pearls

- What fibrosing dermopathy may be associated with gadolinium exposure?

In rare cases, exposure to gadolinium, most often during an MRI examination, can result in nephrogenic systemic fibrosis, a fibrotic process that mainly affects the skin but also affects internal organs; lung fibrosis, heart infiltration, and neuropathy have been reported. Nephrogenic systemic fibrosis typically occurs in patients with severe impairment of renal function (with a glomerular filtration rate of <15 ml per minute). Skin changes can develop rapidly after exposure to gadolinium and are associated with burning, pruritis, and hyperpigmentation. The acute phase evolves into progressive fibrosis involving the dermis and deep soft tissue. The skin feels marblelike, and large plaques are present that usually involve the legs, less commonly involve the arms and trunk, and spare the face. Severe flexion contractures of joints result from fibrosis of deep soft tissue. Dermal fibrosis and interstitial mucin deposition with little or no inflammatory infiltrate are seen on biopsy.

- What are the clinical features of eosinophilic fasciitis?

Eosinophilic fasciitis (Shulman’s syndrome) has been associated with hematologic diseases, including multiple myeloma. In patients with this disorder, there is a rapid onset of skin changes on the arms and legs and sometimes the trunk, with sparing of the face and hands. Fibrosis of deep soft tissue in the fascia leads to contractures; dimpling of the skin (peau d’orange), particularly of the upper inner arms and forearms, is typical. Systemic disease is uncommon, but an inflammatory rheumatoid-like arthritis can be seen. Eosinophilia is present in approximately 80% of cases, and testing for antinuclear antibodies is negative.

Morning Report Questions

Q: What is scleromyxedema?

A: Scleromyxedema is a form of lichen myxedematosus (papular mucinosis) that is almost always associated with IgG MGUS [monoclonal gammopathy of undetermined significance]. This rare disorder has four diagnostic criteria: a generalized papular and sclerodermoid eruption, a triad of findings on microscopic examination of skin-biopsy specimens (mucin deposition, fibroblast proliferation, and fibrosis), a monoclonal gammopathy, and absence of a thyroid disorder. Involvement of the skin of the face, including papules on the neck, glabella, and postauricular area, is almost always present; the limbs and back can also be affected. Linear streaks of papules are characteristic of scleromyxedema, and hyperpigmentation is rare and mild. Systemic disease is common and can have neurologic, musculoskeletal, cardiac, gastrointestinal, pulmonary, and hematologic manifestations. Inflammatory polyarthritis may also occur. In addition, acute renal crisis has been reported in patients with scleromyxedema; in such cases, findings consistent with thrombotic microangiopathic anemia, including narrowed glomerular capillaries, endothelial proliferation, and microthrombi, are seen.

Q: What histologic findings and ancillary studies help differentiate among the fibrosing dermopathies?

A: Fibrosing dermopathies are a group of diseases with overlapping clinicopathological features. Assessment of subcutaneous involvement and dermal fibroblast cellularity on routine histologic examination can help to differentiate among these conditions. Useful ancillary studies include colloidal iron staining to assess for mucin deposition, elastic-tissue staining to assess the quality and quantity of elastic fibers, and immunohistochemical staining to assess for CD34 expression in dermal spindle cells.

Table 2. Clinical, Laboratory, and Histologic Features of Scleroderma, Scleromyxedema, and This Case.

Bioterrorism-Related Conditions

Posted by Carla Rothaus • March 6th, 2015

The agents most likely to be used in bioterrorism attacks are reviewed in a new Review Article, “Clinical Management of Potential Bioterrorism-Related Conditions,” along with the clinical syndromes they produce and their treatment.  This article comes from University of Pittsburgh’s Drs. Amesh Adalja, Eric Toner, and Thomas Inglesby.

On the basis of historical incidents coupled with information on ease of dissemination, contagiousness, mortality rates, public health impact, ability to engender panic, and the need for special preparedness, the Centers for Disease Control and Prevention (CDC) stratifies pathogens and toxins into three risk categories — A, B, and C — with category A meriting the highest level of concern and preparedness.

Clinical Pearls

- What is the most lethal form of anthrax, and what are its clinical features?

Anthrax is caused by infection with the spore-forming, exotoxin-producing, gram-positive bacillus Bacillus anthracis. In humans, three forms of anthrax are recognized: cutaneous (the most common), gastrointestinal and inhalational (the most deadly).

Inhalational anthrax results from the inhalation of bacterial spores that later germinate in the lung. Disease onset begins with nonspecific influenza-like symptoms; with the exception that rhinorrhea is absent. After the disease progresses through this stage, which lasts hours to days, a severe advanced phase occurs and includes high fever, shock, and respiratory distress. Inhalational anthrax does not cause pneumonia but nevertheless can progress to the acute respiratory distress syndrome. Hemorrhagic mediastinitis, as well as toxin-laden pleural and pericardial effusions, can be present. Spread of the disease to the meninges, with resultant hemorrhagic meningitis, is a frequent complication of systemic forms of anthrax, occurring in up to 50% of cases; this complication confers a higher degree of mortality. Traditionally, inhalational anthrax has carried a 90% case fatality rate; however, during the 2001 attacks in which anthrax spores were sent through the U.S. mail, the case fatality rate was halved, to 45%. The reason for the decrement in mortality is probably multifactorial and includes the benefits of modern critical care, the drainage of toxin-laden pleural effusions, and the use of antimicrobial therapies.

- What is the recommended treatment for systemic anthrax?

Anthrax-specific treatments include combination antimicrobial therapy. If meningitis has not been ruled out, the CDC recommends a regimen including a fluoroquinolone, such as ciprofloxacin; a drug that inhibits protein synthesis, such as linezolid; and a drug that penetrates the central nervous system, such as meropenem. If meningitis has been ruled out with the use of a lumbar puncture, a two-drug regimen that includes a fluoroquinolone plus linezolid or clindamycin is recommended. The CDC recommends antitoxin as adjunctive treatment in cases of systemic anthrax.

Morning Report Questions

Q: What are the clinical features of smallpox, and are there any FDA [Food and Drug Administration]-licensed therapies?

A: Infection with the smallpox virus, variola, occurs through droplet or aerosol exposure. After an incubation period of 10 to 14 days, a prodrome of fever and constitutional symptoms begins. Rash appears 1 to 4 days after the onset of fever. The rash is characteristically centrifugal, with lesions progressing synchronously from macules to papules to vesicles (umbilicated) to pustules to scabs over a period of a couple weeks. A person is contagious during the period when the rash is present, and infectiousness ceases after the scabs have sloughed. The fatality rate of smallpox is approximately 25%, and severe complications such as blindness can also occur. There are currently no FDA-licensed treatments for smallpox, although two compounds are in late development stages. Indications for their use are not yet available, but their availability during an outbreak would probably be through emergency-use authorization.

Q: What type of illness would result from a deliberate release of tularemia, and how might it be treated?

A: Several forms of tularemia occur; however, a deliberate release would be expected to cause pneumonic tularemia rather than the more common ulceroglandular form. After an average incubation period of 3 to 5 days, pneumonic tularemia would manifest with signs and symptoms similar to those of community-acquired pneumonia, including fever, cough, and dyspnea. However, septic shock, acute respiratory distress syndrome, and respiratory failure can ensue. Because there is no distinguishing characteristic of pneumonic tularemia, clinical suspicion must be high. The treatment of tularemia consists of a 10-day course of an aminoglycoside antibiotic, such as streptomycin or gentamicin. Ciprofloxacin and doxycycline are alternatives.

Itching for a Diagnosis

Posted by Carla Rothaus • March 6th, 2015

In the latest Clinical Problem-Solving article, a 58-year-old woman presented with a 2-week history of generalized pruritus. She also reported having fatigue, dizziness, and decreased appetite. A week before the onset of symptoms, a mild upper respiratory tract infection had developed.

Collapsing glomerulopathy is one of the few causes of the nephrotic syndrome in which the patient has substantial proteinuria combined with profound renal failure.

Clinical Pearls

- What are the criteria for the nephrotic syndrome?

The nephrotic syndrome is classically defined by the triad of heavy proteinuria (>3.5 g over a period of 24 hours), hypoalbuminemia (<3 g per deciliter), and peripheral edema. Patients with nephrotic syndrome also often have hyperlipidemia.

- What are secondary causes of the nephrotic syndrome in adults?

Although patients with primary kidney diseases such as minimal-change disease, focal segmental glomerulosclerosis, and membranous nephropathy present with the nephrotic syndrome, approximately half of the cases of an overt nephrotic syndrome or urine protein levels in the nephrotic range in adults are caused by systemic diseases (e.g., diabetes mellitus [the most common cause of a secondary nephrotic syndrome], systemic lupus erythematosus, and monoclonal gammopathies) or are postinfectious (e.g., hepatitis B virus, hepatitis C virus, and HIV [human immunodeficiency virus]).

Morning Report Questions

Q: What is collapsing glomerulopathy?

A: In the early 1980s, collapsing glomerulopathy was a relatively frequent diagnosis in persons with HIV infection (so-called HIV-associated nephropathy). Subsequently, a similar kidney lesion was described in HIV-negative patients, and the condition was termed collapsing glomerulopathy. In collapsing glomerulopathy, the glomerular lesions are often characterized by segmental or global glomerular collapse without sclerosis or hyalinosis. Although collapsing glomerulopathy has been categorized as a variant of focal segmental glomerulosclerosis, its unique clinical manifestation and histologic characteristics have suggested that it is more appropriately considered to be a distinct clinicopathological entity. Both the degree of proteinuria and the rate of progression of the kidney failure are more pronounced in collapsing glomerulopathy than in classical focal segmental glomerulosclerosis. Collapsing glomerulopathy may recur or occur anew after renal transplantation. Treatment of patients with collapsing glomerulopathy is challenging, and the overall prognosis is poor.

Q: What diseases or risk factors are associated with the development of collapsing glomerulopathy?

A: It has been suggested that variants of APOL1 may predispose persons of African ancestry to collapsing glomerulopathy, but further research is needed. Like other glomerulopathies, collapsing glomerulopathy may be idiopathic or secondary. The most commonly recognized underlying cause has been HIV infection. Other possibilities include other infections (parvovirus B19, cytomegalovirus, and HCV); drugs (bisphosphonates, interferon-alpha, and valproic acid); autoimmune disorders (e.g., systemic lupus erythematosus); thrombotic microangiopathies; and hematologic disorders (e.g., the hemophagocytic syndrome).

Improved Air Quality and Lung Development in Children

Posted by Chana Sacks • March 4th, 2015

In 1905, the Public Health Congress convened in London, where Dr. Henry Antoine des Voeux presented a paper entitled “Fog and Smoke.”  In it, he described the characteristic black smoky fog – or “smog” – that enveloped London and many of the world’s other urban centers.  Credited with coining this new term, Dr. des Voeux introduced a word that over the next century would become synonymous with the traffic congestion of the sprawling Los Angeles metropolitan area.

Driven by increasing recognition of the adverse health effects of air pollution (and perhaps a dislike of the dubious distinction of being home to America’s most polluted region), California instituted aggressive pollution-reduction strategies. Many of these policies have been successful, and over the past few decades, air pollution levels have been decreasing. But do these improvements in air quality lead to important, measurable benefits for people living in southern California?

A new study published in NEJM suggests they do, demonstrating an association between decreasing pollution and improving lung function growth in children.  The study included cohorts of children in five communities, from three separate time periods enrolled as part of the 20-year Children’s Health Study.  The enrolled children were near 11 years of age at the start, and the cohorts were each followed with longitudinal lung function tests for four years (1994-1998, 1997-2001, and 2007-2011), as this is the period when the lungs grow substantially in size.  The investigators examined the association between levels of nitrogen dioxide, particulate matter, and ozone and children’s lung function growth during the same period.

The results: for nitrogen dioxide, every decrease of 14.1 parts per billion was associated with a 91.4mL increase in the mean four-year growth of FEV1 (P<0.001). There were similar improvements in FVC.  This association was also demonstrated for particulate matter, but not for ozone.  Significant improvements were observed for boys and girls and for children with and without asthma. The authors conclude that these data suggest “that all children have the potential to benefit from improvements in air quality.”

A separate analysis revealed that the proportion of 15-year-old children with low FEV1 (that is, <80% predicted) declined over the study period as air quality improved: 7.9% in first cohort, 6.3% in the second and 3.6% in the most recent (P < 0.005).

Editor-in-Chief Dr. Jeffrey Drazen notes that “while an observational study alone cannot determine causation, these data are compelling and add to an important body of evidence suggesting that incremental improvements in pollution have important clinical benefits.”

In an accompanying editorial, Douglas Dockery and James Ware of the Harvard School of Public Health agree, writing, “Some have argued that the substantial improvements in air quality over the past 40 years are sufficient to protect public health…However, the current report and other studies suggest that further improvement in air quality may have beneficial public health effects.”  This study, then, is good news, but there may still be work left to do to protect our children’s lungs from the smoky fog.

Also, watch the Quick Take video summary of these research results.

Peanut Consumption in Infants

Posted by Carla Rothaus • February 27th, 2015

Children 4 to 11 months of age who were at high risk for development of peanut allergy were assigned to consumption or avoidance of peanuts until 60 months of age. Peanut allergy was more than five times as likely to develop in children assigned to peanut avoidance. (View a 1-minute Video Summary.  And, ask the authors and experts about the study in the NEJM Group Open Forum on

Several years ago, the Learning Early about Peanut Allergy (LEAP) researchers found that the risk of the development of peanut allergy was 10 times as high among Jewish children in the United Kingdom as it was in Israeli children of similar ancestry. This observation correlated with a striking difference in the time at which peanuts are introduced in the diet in these countries: in the United Kingdom infants typically do not consume peanut-based foods in the first year of life, whereas in Israel, peanut-based foods are usually introduced in the diet when infants are approximately 7 months of age. The LEAP trial was conceived to determine whether the early introduction of dietary peanut could serve as an effective primary and secondary strategy for the prevention of peanut allergy.

Clinical Pearls

- Is there evidence that eliminating allergenic foods from the diets of infants can prevent future allergy?

Clinical practice guidelines from the United Kingdom in 1998 and from the United States in 2000 recommended the exclusion of allergenic foods from the diets of infants at high risk for allergy and from the diets of their mothers during pregnancy and lactation. However, studies in which food allergens have been eliminated from the diet have consistently failed to show that elimination from the diet prevented the development of IgE-mediated food allergy.

- Does peanut consumption as compared with peanut avoidance decrease peanut allergy in at-risk infants with no preexisting peanut sensitivity?

The study by Du Toit et al. included infants aged 4 to 11 months who had severe eczema, egg allergy, or both. Among the 542 infants in the group with a negative result on an initial skin-prick test assessing preexisting peanut sensitivity, 530 (97.8%) could be evaluated for the primary outcome and were included in the intention-to-treat analysis. At 60 months of age, 13.7% of the avoidance group and 1.9% of the consumption group were allergic to peanuts; this absolute difference in risk of 11.8 percentage points (95% confidence interval [CI], 3.4 to 20.3; P<0.001) represents an 86.1% relative reduction in the prevalence of peanut allergy.

Morning Report Questions

Q: Does peanut consumption as compared with peanut avoidance decrease the development of peanut allergy in at-risk infants who have preexisting peanut sensitivity?

A: All 98 children in the group with positive results on the initial skin-prick test were evaluated and were included in the intention-to-treat analysis. At 60 months of age, 35.3% of the avoidance group and 10.6% of the consumption group were allergic to peanuts; the absolute difference in risk of 24.7 percentage points (95% CI, 4.9 to 43.3; P=0.004) represents a 70% relative reduction in the prevalence of peanut allergy.

Figure 2. Primary Outcome.

Q: How do levels of peanut-specific IgE, IgG, and IgG4 in infants who consume peanuts compare to those of infants who do not consume peanuts?

A: At 60 months, the number of participants with markedly elevated levels of peanut-specific IgE titers was higher in the peanut-avoidance group than in the consumption group. In contrast, the peanut-consumption group showed a significantly greater and earlier increase in levels of peanut-specific IgG and IgG4; this effect mirrors the immunologic changes seen in successful allergen immunotherapy. Furthermore, in the avoidance group, unless peanut-specific IgE levels were very high, elevated IgG4 levels were associated with the absence of an allergic reaction to peanuts. Both observations indicate that IgG4 is associated with a protective role against the development of allergy.

A Man with Oral Ulcers

Posted by Carla Rothaus • February 27th, 2015

In the latest Case Record of the Massachusetts General Hospital, a 25-year-old man presented with oral ulcers and odynophagia. On examination, there were scattered pink papules and plaques on the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins. A diagnostic procedure was performed.

Behcet’s disease affects young adults, usually starting during the third decade of life.

Clinical Pearls

- What is Behcet’s disease?

Behcet’s disease is a rare rheumatologic condition characterized by recurrent oral and genital ulcers, rash, inflammatory eye disease, and vasculitis. This disease occurs worldwide, but its incidence is highest in the Far East and Middle East regions and in countries around the Mediterranean basin.

- What are the characteristics of the oral and genital lesions that occur in patients with Behcet’s disease?

Mouth lesions that are indistinguishable from simple aphthous ulcers are seen in virtually all affected patients and may be located in the epithelial mucosa that covers the lips, cheeks, gums, tongue, palate, floor of the mouth, and pharynx, including the tonsils. However, as compared with common aphthous ulcers, oral ulcers related to Behcet’s disease generally occur in groups, are larger, and take a longer amount of time to heal, usually without scarring. Genital ulcers, which have a “punched-out” appearance, develop in approximately 80% of patients, typically involve the penile shaft and scrotum in men, and tend to heal within a month, leaving a scar; in some cases, genital ulcerations associated with Behcet’s disease can occur in the inguinal area and perineum.

Morning Report Questions

Q: What are additional clinical features of Behcet’s disease?

A: Additional cutaneous manifestations develop in the majority of patients with Behcet’s disease at some point during the course of the illness; these can include papulopustular, pseudofollicular, and acneiform eruptions and lesions resembling erythema nodosum. Arthralgias and nonerosive oligoarthritis are commonly described. In nearly half the cases of Behcet’s disease, a sterile pustule is formed within 48 hours after minor skin trauma (e.g., needle stick); this is especially common among patients from countries in the Far East or Middle East regions. This reaction, called the pathergy phenomenon, is not sensitive for but is highly specific for the diagnosis of Behcet’s disease. Inflammatory eye involvement may be seen in 25 to 75% of patients with Behcet’s disease and may be manifested as uveitis, retinal vasculitis, or optic neuritis. Less frequent manifestations include lesions involving the central nervous system, esophagogastrointestinal inflammation leading to mucosal erosions, cardiac involvement (e.g., pericarditis or myocarditis), epididymitis, and vasculitis with varying sizes of blood vessels, which may confer a predisposition to arterial and venous thrombosis.

Q: How is Behcet’s disease diagnosed and treated?

A: The diagnosis of Behcet’s disease is typically made on the basis of clinical evidence, but a skin or mucous-membrane biopsy may be performed to help confirm the diagnosis. Behcet’s disease has characteristics of both autoimmune and autoinflammatory diseases.

Treatment may target either the autoimmune or the autoinflammatory aspects of the disease, or it may target both. In addition, the choice of treatment is frequently determined on the basis of organ involvement. Mucocutaneous lesions are the most frequently occurring feature in patients with Behcet’s disease, although arthritis occurs in up to half the cases. Colchicine is often used to control these manifestations; clinical trials have shown its efficacy in treating both inflammatory arthritis and skin lesions. Isolated skin and genital lesions may be treated with topical glucocorticoids, and in cases of more severe skin involvement, azathioprine, thalidomide, and tumor necrosis factor inhibitors are alternative options, although toxic effects associated with thalidomide may preclude its use.

Systemic glucocorticoids, which are frequently used to treat Behcet’s disease, are probably more effective in controlling erythema nodosum than in managing oral and genital ulcers. Treatment of eye involvement in patients with Behcet’s disease is of paramount importance, because blindness or impaired vision may develop in up to 25% of affected patients.

Table 2. International Study Group Criteria for the Diagnosis of Behcet’s Disease.

New Conversations on the NEJM Group Open Forum

Posted by Jennifer Zeis • February 26th, 2015

NEJM Group Open Forum

Now on the NEJM Group Open Forum, NEJM authors and experts are discussing:

NEJM Group Open Forum (#NEJMForum) is a series of live discussions intended to generate active conversation around important — and sometimes controversial — ideas. NEJM Group and joined together to create the forum, and physicians and medical students are welcome to read the discussion boards or join in the conversation.

Medstro recently added one-click sign up with your Facebook, LinkedIn, or Twitter accounts to make it faster and easier to join.

What are you waiting for? Join the discussion now! The peanut allergy forum closes March 4, the precision medicine forum closes March 5, and the mitochondrial replacement forum opens March 3.