Doug Brunk is a San Diego-based award-winning reporter who began covering health care in 1991. Before joining the company, he wrote for the health sciences division of Columbia University and was an associate editor at Contemporary Long Term Care magazine when it won a Jesse H. Neal Award. His work has been syndicated by the Los Angeles Times and he is the author of two books related to the University of Kentucky Wildcats men's basketball program. Doug has a master’s degree in magazine journalism from the S.I. Newhouse School of Public Communications at Syracuse University. Follow him on Twitter @dougbrunk.

Tips on how to differentiate CLE from dermatomyositis

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Tips on how to differentiate CLE from dermatomyositis

NEWPORT BEACH, CALIF. – Cutaneous lupus erythematosus and dermatomyositis look identical on histology, so the diagnosis boils down to your clinical exam.

At the annual meeting of the Pacific Dermatologic Association, Nicole Fett, MD, provided clinical pearls on how to differentiate between the two conditions. She began by discussing the case of a 28-year-old female who presents with fatigue, arthralgias, myalgias, photosensitivity, and erythematous scaling papules coalescing into plaques on the face (sparing the nasolabial folds), neck, chest, and bilateral arms and hands (sparing the dorsal hand joints). Earlier in the week, she saw her primary care physician, who ordered an antinuclear antibody test, which was positive at 1:640.

 

Dr. Nicole Fett

This patient, who was previously healthy, has no known allergies, is on a prenatal vitamin, does not use any drugs or alcohol, is a nonsmoker, and has a family history of autoimmunity, said Dr. Fett, of the department of dermatology at Oregon Health and Science University, Portland. The woman’s clinical findings were most consistent with acute cutaneous lupus erythematosus (CLE).

“Acute CLE spares the nasolabial folds, whereas patients who have dermatomyositis have involvement of the nasolabial folds,” she noted. Examining the hands can also provide clues, as patients with CLE have involvement of the interjoint spaces and sparing of the joints, while patients with dermatomyositis have involvement of the joints and sparing of the interjoint spaces. In addition, patients with dermatomyositis are more likely to have lower extremity involvement, compared with patients who have CLE. “Patients with dermatomyositis will tend to have diffuse scalp involvement that is itchy,” Dr. Fett added. “That is not something you commonly see in cutaneous lupus.”

Other common features of CLE include concomitant discoid lupus erythematosus or another lupus subtype, and mucosal ulcerations, while other common features of dermatomyositis include the Shawl sign and poikiloderma.

The recommended review of systems and exams to assess for systemic lupus erythematosus in CLE patients include asking about photosensitivity, looking for mucosal ulcers, assessing for arthritis, asking about a history of pericarditis or pleuritis, as well as asking about a history of low blood counts, kidney disease, seizures, and malar rash. On cutaneous exam, look for signs of concomitant CLE subtypes, assess for nonspecific cutaneous lupus findings, and evaluate the mucosa. Recommended labs include a complete blood count and an additional workup for anemia, complete metabolic panel, urinalysis, erythrocyte sedimentation rate, C-reactive protein, antinuclear antibody, complement C3 and C4, and antiphospholipid and anticardiolipin antibodies.

The recommended review of systems and exams in patients with dermatomyositis, she said, include assessing for dysphonia/dysphagia, weakness with overhead tasks, weakness when climbing stairs or standing from a seated position, cough, shortness of breath, or dyspnea on exertion, fever, weight loss, night sweats, and pruritus. “When I think about the dermatomyositis patient I think not only about their skin, but about their muscles, lungs and risk of malignancy,” Dr. Fett said. “They have a high risk for developing interstitial lung disease, and about 25% of adult patients are going to have an underlying malignancy.”

She reported having no financial disclosures.

[email protected]

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NEWPORT BEACH, CALIF. – Cutaneous lupus erythematosus and dermatomyositis look identical on histology, so the diagnosis boils down to your clinical exam.

At the annual meeting of the Pacific Dermatologic Association, Nicole Fett, MD, provided clinical pearls on how to differentiate between the two conditions. She began by discussing the case of a 28-year-old female who presents with fatigue, arthralgias, myalgias, photosensitivity, and erythematous scaling papules coalescing into plaques on the face (sparing the nasolabial folds), neck, chest, and bilateral arms and hands (sparing the dorsal hand joints). Earlier in the week, she saw her primary care physician, who ordered an antinuclear antibody test, which was positive at 1:640.

 

Dr. Nicole Fett

This patient, who was previously healthy, has no known allergies, is on a prenatal vitamin, does not use any drugs or alcohol, is a nonsmoker, and has a family history of autoimmunity, said Dr. Fett, of the department of dermatology at Oregon Health and Science University, Portland. The woman’s clinical findings were most consistent with acute cutaneous lupus erythematosus (CLE).

“Acute CLE spares the nasolabial folds, whereas patients who have dermatomyositis have involvement of the nasolabial folds,” she noted. Examining the hands can also provide clues, as patients with CLE have involvement of the interjoint spaces and sparing of the joints, while patients with dermatomyositis have involvement of the joints and sparing of the interjoint spaces. In addition, patients with dermatomyositis are more likely to have lower extremity involvement, compared with patients who have CLE. “Patients with dermatomyositis will tend to have diffuse scalp involvement that is itchy,” Dr. Fett added. “That is not something you commonly see in cutaneous lupus.”

Other common features of CLE include concomitant discoid lupus erythematosus or another lupus subtype, and mucosal ulcerations, while other common features of dermatomyositis include the Shawl sign and poikiloderma.

The recommended review of systems and exams to assess for systemic lupus erythematosus in CLE patients include asking about photosensitivity, looking for mucosal ulcers, assessing for arthritis, asking about a history of pericarditis or pleuritis, as well as asking about a history of low blood counts, kidney disease, seizures, and malar rash. On cutaneous exam, look for signs of concomitant CLE subtypes, assess for nonspecific cutaneous lupus findings, and evaluate the mucosa. Recommended labs include a complete blood count and an additional workup for anemia, complete metabolic panel, urinalysis, erythrocyte sedimentation rate, C-reactive protein, antinuclear antibody, complement C3 and C4, and antiphospholipid and anticardiolipin antibodies.

The recommended review of systems and exams in patients with dermatomyositis, she said, include assessing for dysphonia/dysphagia, weakness with overhead tasks, weakness when climbing stairs or standing from a seated position, cough, shortness of breath, or dyspnea on exertion, fever, weight loss, night sweats, and pruritus. “When I think about the dermatomyositis patient I think not only about their skin, but about their muscles, lungs and risk of malignancy,” Dr. Fett said. “They have a high risk for developing interstitial lung disease, and about 25% of adult patients are going to have an underlying malignancy.”

She reported having no financial disclosures.

[email protected]

NEWPORT BEACH, CALIF. – Cutaneous lupus erythematosus and dermatomyositis look identical on histology, so the diagnosis boils down to your clinical exam.

At the annual meeting of the Pacific Dermatologic Association, Nicole Fett, MD, provided clinical pearls on how to differentiate between the two conditions. She began by discussing the case of a 28-year-old female who presents with fatigue, arthralgias, myalgias, photosensitivity, and erythematous scaling papules coalescing into plaques on the face (sparing the nasolabial folds), neck, chest, and bilateral arms and hands (sparing the dorsal hand joints). Earlier in the week, she saw her primary care physician, who ordered an antinuclear antibody test, which was positive at 1:640.

 

Dr. Nicole Fett

This patient, who was previously healthy, has no known allergies, is on a prenatal vitamin, does not use any drugs or alcohol, is a nonsmoker, and has a family history of autoimmunity, said Dr. Fett, of the department of dermatology at Oregon Health and Science University, Portland. The woman’s clinical findings were most consistent with acute cutaneous lupus erythematosus (CLE).

“Acute CLE spares the nasolabial folds, whereas patients who have dermatomyositis have involvement of the nasolabial folds,” she noted. Examining the hands can also provide clues, as patients with CLE have involvement of the interjoint spaces and sparing of the joints, while patients with dermatomyositis have involvement of the joints and sparing of the interjoint spaces. In addition, patients with dermatomyositis are more likely to have lower extremity involvement, compared with patients who have CLE. “Patients with dermatomyositis will tend to have diffuse scalp involvement that is itchy,” Dr. Fett added. “That is not something you commonly see in cutaneous lupus.”

Other common features of CLE include concomitant discoid lupus erythematosus or another lupus subtype, and mucosal ulcerations, while other common features of dermatomyositis include the Shawl sign and poikiloderma.

The recommended review of systems and exams to assess for systemic lupus erythematosus in CLE patients include asking about photosensitivity, looking for mucosal ulcers, assessing for arthritis, asking about a history of pericarditis or pleuritis, as well as asking about a history of low blood counts, kidney disease, seizures, and malar rash. On cutaneous exam, look for signs of concomitant CLE subtypes, assess for nonspecific cutaneous lupus findings, and evaluate the mucosa. Recommended labs include a complete blood count and an additional workup for anemia, complete metabolic panel, urinalysis, erythrocyte sedimentation rate, C-reactive protein, antinuclear antibody, complement C3 and C4, and antiphospholipid and anticardiolipin antibodies.

The recommended review of systems and exams in patients with dermatomyositis, she said, include assessing for dysphonia/dysphagia, weakness with overhead tasks, weakness when climbing stairs or standing from a seated position, cough, shortness of breath, or dyspnea on exertion, fever, weight loss, night sweats, and pruritus. “When I think about the dermatomyositis patient I think not only about their skin, but about their muscles, lungs and risk of malignancy,” Dr. Fett said. “They have a high risk for developing interstitial lung disease, and about 25% of adult patients are going to have an underlying malignancy.”

She reported having no financial disclosures.

[email protected]

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Current Tx for blistering disorders lacks evidence-based science

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Current Tx for blistering disorders lacks evidence-based science

NEWPORT BEACH, CALIF. – Current treatment of autoimmune blistering diseases is not backed by evidence-based medicine and solid randomized, controlled trials, according to David T. Woodley, MD.

“These are rare diseases; there’s no consensus on the treatment of choice,” Dr. Woodley said at the annual meeting of the Pacific Dermatologic Association.

Dr. Woodley, professor of dermatology at the University of Southern California, Los Angeles, limited his discussion to pemphigus vulgaris (PV), pemphigus foliaceus (PF), and bullous pemphigoid (BP). The histologic hallmark of PV and PF is acantholysis. “Because these are intraepidermal blistering diseases, you don’t see the blister very often; maybe you’ll have a few intact loose sacklike blisters, but you mostly see erosions and crusting,” he said. “PV often only begins with mouth lesions.”

Dr. David T. Woodley

Work-up for a suspected autoimmune blistering disease includes a physical exam, histology, direct and indirect immunofluorescence, and serologic tests. The diagnosis should be based on the target autoantigen in the skin. PV and PF can appear identical on direct immunofluorescence, even though the blister cleavage plane is very high in PF and usually just above the basal keratinocytes in PV. “PF can have an intercellular keratinocyte cell surface staining pattern throughout the full epidermis or sometimes only the upper epidermal layers,” Dr. Woodley said.

At an international meeting on pemphigus in 2015, Dr. Woodley and his associates presented results from an ongoing study that is following 44 pemphigus patients at Keck Hospital of USC (a private university health care system) and 40 patients at Los Angeles County and USC Medical Center (a public safety net health care system). “The question we asked was, When the same doctors treat patients with a serious complicated disease requiring lots of details and follow-up at two very different health care systems, were there any differences in the outcomes of these patients?”

They found that the rates of clinical and immunologic remission were identical at both hospitals. However, at the county hospital, there was a higher incidence of relapses (59% vs. 30%). In addition, complications between the county and private hospitals differed in terms of hyperglycemia (38% vs. 11%, respectively), infections (79% vs. 37%), deaths (1 vs. none), medication dosage nonadherence (68% vs. 22%), and inappropriate discontinuation of one or more medications (68% vs. 15%). “Current research goals are to determine what factors cause medication compliance and noncompliance,” he said.

Dr. Woodley noted that one autoimmune blistering disease can evolve into another because of the phenomenon of epitope spreading. “The concept is that inflammation from one autoimmune blistering disease creates skin injury and reveals new neoautoantigens that get recognized by the patient’s immune system,” he said.

For example, a patient who had PF and high-titer autoantibodies to desmoglein 1 after a couple of years began to have blisters and erosions in her mouth, which is not supposed to happen in PF. Immunologic testing of this patient showed that in addition to antibodies against desmoglein 1, she began making high-titer autoantibodies against desmoglein 3 and had transformed into PV.

Bullous pemphigoid is another well-characterized autoimmune bullous disease that usually occurs in elderly patients. The blister is beneath the epidermis at the dermal-epidermal junction. These patients may have oral involvement. BP is characterized by tense subepidermal bullae on inflammatory bases. Histology reveals epidermal-dermal separation, many eosinophils and mast cells, and sometimes many polymorphonuclear leukocytes. “Many of these patients have very high IgE antibodies as well as IgG,” he said.

Features of BP include IgG and C3 deposits at the dermal-epidermal junction by direct immunofluorescence and by indirect immunofluorescence. “On salt-split human skin substrate, these antibodies bind to the epidermal roof of the separation and not to the dermal floor,” Dr. Woodley said. “You can send off the patient’s serum for ELISA [enzyme-linked immunosorbent assay] testing to detect autoantibodies against the BP230 antigen and the BP180 antigen to confirm the diagnosis. Autoantibodies to the BP180 antigen often correlate with the patient’s disease activity. The sensitivity of indirect immunofluorescence and ELISA are both above 95%.”

BP can present with urticarial plaques and pruritus and without blisters. Also, recent research has demonstrated that BP can present with just pruritus and no skin lesions. “So that’s something to keep in mind in refractory pruritus patients,” he said.

The incidence of BP seems to be increasing, from an estimated 7 cases per million in 1995 to 43 cases per million in 2008, Dr. Woodley said. “It may be that it is associated with some drugs like loop diuretics and spironolactone, but the precise reason is not known,” he said. “If your patient has dementia or Parkinson’s disease, he or she has a fourfold increased chance that they will have BP, because the BP180 and BP230 antigens are also in neuronal cells. Parkinson’s patients are known to make antibodies to the BP180 antigen, but not to the NC16A domain of the BP180 antigen. The development of BP in a Parkinson’s patient occurs when he or she begins to also make autoantibodies against the NC16A domain.”

 

 

The standard of treatment for autoimmune blistering diseases is prednisone 0.7-2 mg/kg. Nonsteroidal immunosuppressive agents are also helpful, including methotrexate, azathioprine, cyclophosphamide, and mycophenolate mofetil. Emerging evidence suggests that rituximab is the drug of choice for PV and PF, and should be the first-line therapy. Rituximab is a chimeric monoclonal antibody that targets CD20–positive B lymphocytes. “It removes cells that are ready to transform into autoantibody-producing short-lived plasma cells,” Dr. Woodley said. “The depletion lasts 6-12 months.”

Another new development in BP is the use of omalizumab, a monoclonal antibody to IgE. “Omalizumab inhibits the IgE antibody binding to the BP180,” Dr. Woodley said.

“It’s thought that the BP180 antigen is released from basal keratinocytes into the high papillary dermis. In BP patients, there are numerous mast cells at that location. IgE binds to the mast cells, which have IgE receptors on their surface, and in the presence of the BP180 antigen, forms dimers on the mast cells, and causes them to release inflammatory cytokines, some of which recruit eosinophils. This is likely why BP is such an inflammatory disorder. You cannot follow the IgE levels; you have to follow the eosinophils. The IgE is still high, but it’s nullified and inactive.”

Other biologics that have been successfully used in PV, PF, and BP include tumor necrosis factor–alpha inhibitors and rituximab (Rituxan). Common dosing for rituximab is 325 mg/m2 per week for 4 weeks. Infusion reactions are the most common side effect, he said, but other reported adverse reactions include infections, transient hypogammaglobulinemia, neutropenia, deep vein thrombosis, and pulmonary embolism. “The incidence of side effects seems to be going down, because we are now premedicating patients with antihistamines and IV hydrocortisone before giving them rituximab,” Dr. Woodley noted.

The development of progressive multifocal leukoencephalopathy has also been reported with the use of rituximab. “This is exceedingly rare with rituximab but has been described, and this is what keeps doctors who use this drug awake at night,” he said.

Elderly patients with mild BP sometimes can get by without using immunosuppressive agents to manage their disease. One option is potent topical steroids plus niacinamide 0.5-2 g after each meal as an anti-inflammatory B vitamin. “Doxycycline 100 mg b.i.d. also works to inhibit neutrophils,” he said. “Antihistamines can also be helpful, and some French dermatologists have found total body clobetasol to be useful.”

Dr. Woodley disclosed that he holds patents on human recombinant type VII collagen. He is also a consultant for Shire Pharmaceuticals and a speaker for Biofusion.

[email protected]

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NEWPORT BEACH, CALIF. – Current treatment of autoimmune blistering diseases is not backed by evidence-based medicine and solid randomized, controlled trials, according to David T. Woodley, MD.

“These are rare diseases; there’s no consensus on the treatment of choice,” Dr. Woodley said at the annual meeting of the Pacific Dermatologic Association.

Dr. Woodley, professor of dermatology at the University of Southern California, Los Angeles, limited his discussion to pemphigus vulgaris (PV), pemphigus foliaceus (PF), and bullous pemphigoid (BP). The histologic hallmark of PV and PF is acantholysis. “Because these are intraepidermal blistering diseases, you don’t see the blister very often; maybe you’ll have a few intact loose sacklike blisters, but you mostly see erosions and crusting,” he said. “PV often only begins with mouth lesions.”

Dr. David T. Woodley

Work-up for a suspected autoimmune blistering disease includes a physical exam, histology, direct and indirect immunofluorescence, and serologic tests. The diagnosis should be based on the target autoantigen in the skin. PV and PF can appear identical on direct immunofluorescence, even though the blister cleavage plane is very high in PF and usually just above the basal keratinocytes in PV. “PF can have an intercellular keratinocyte cell surface staining pattern throughout the full epidermis or sometimes only the upper epidermal layers,” Dr. Woodley said.

At an international meeting on pemphigus in 2015, Dr. Woodley and his associates presented results from an ongoing study that is following 44 pemphigus patients at Keck Hospital of USC (a private university health care system) and 40 patients at Los Angeles County and USC Medical Center (a public safety net health care system). “The question we asked was, When the same doctors treat patients with a serious complicated disease requiring lots of details and follow-up at two very different health care systems, were there any differences in the outcomes of these patients?”

They found that the rates of clinical and immunologic remission were identical at both hospitals. However, at the county hospital, there was a higher incidence of relapses (59% vs. 30%). In addition, complications between the county and private hospitals differed in terms of hyperglycemia (38% vs. 11%, respectively), infections (79% vs. 37%), deaths (1 vs. none), medication dosage nonadherence (68% vs. 22%), and inappropriate discontinuation of one or more medications (68% vs. 15%). “Current research goals are to determine what factors cause medication compliance and noncompliance,” he said.

Dr. Woodley noted that one autoimmune blistering disease can evolve into another because of the phenomenon of epitope spreading. “The concept is that inflammation from one autoimmune blistering disease creates skin injury and reveals new neoautoantigens that get recognized by the patient’s immune system,” he said.

For example, a patient who had PF and high-titer autoantibodies to desmoglein 1 after a couple of years began to have blisters and erosions in her mouth, which is not supposed to happen in PF. Immunologic testing of this patient showed that in addition to antibodies against desmoglein 1, she began making high-titer autoantibodies against desmoglein 3 and had transformed into PV.

Bullous pemphigoid is another well-characterized autoimmune bullous disease that usually occurs in elderly patients. The blister is beneath the epidermis at the dermal-epidermal junction. These patients may have oral involvement. BP is characterized by tense subepidermal bullae on inflammatory bases. Histology reveals epidermal-dermal separation, many eosinophils and mast cells, and sometimes many polymorphonuclear leukocytes. “Many of these patients have very high IgE antibodies as well as IgG,” he said.

Features of BP include IgG and C3 deposits at the dermal-epidermal junction by direct immunofluorescence and by indirect immunofluorescence. “On salt-split human skin substrate, these antibodies bind to the epidermal roof of the separation and not to the dermal floor,” Dr. Woodley said. “You can send off the patient’s serum for ELISA [enzyme-linked immunosorbent assay] testing to detect autoantibodies against the BP230 antigen and the BP180 antigen to confirm the diagnosis. Autoantibodies to the BP180 antigen often correlate with the patient’s disease activity. The sensitivity of indirect immunofluorescence and ELISA are both above 95%.”

BP can present with urticarial plaques and pruritus and without blisters. Also, recent research has demonstrated that BP can present with just pruritus and no skin lesions. “So that’s something to keep in mind in refractory pruritus patients,” he said.

The incidence of BP seems to be increasing, from an estimated 7 cases per million in 1995 to 43 cases per million in 2008, Dr. Woodley said. “It may be that it is associated with some drugs like loop diuretics and spironolactone, but the precise reason is not known,” he said. “If your patient has dementia or Parkinson’s disease, he or she has a fourfold increased chance that they will have BP, because the BP180 and BP230 antigens are also in neuronal cells. Parkinson’s patients are known to make antibodies to the BP180 antigen, but not to the NC16A domain of the BP180 antigen. The development of BP in a Parkinson’s patient occurs when he or she begins to also make autoantibodies against the NC16A domain.”

 

 

The standard of treatment for autoimmune blistering diseases is prednisone 0.7-2 mg/kg. Nonsteroidal immunosuppressive agents are also helpful, including methotrexate, azathioprine, cyclophosphamide, and mycophenolate mofetil. Emerging evidence suggests that rituximab is the drug of choice for PV and PF, and should be the first-line therapy. Rituximab is a chimeric monoclonal antibody that targets CD20–positive B lymphocytes. “It removes cells that are ready to transform into autoantibody-producing short-lived plasma cells,” Dr. Woodley said. “The depletion lasts 6-12 months.”

Another new development in BP is the use of omalizumab, a monoclonal antibody to IgE. “Omalizumab inhibits the IgE antibody binding to the BP180,” Dr. Woodley said.

“It’s thought that the BP180 antigen is released from basal keratinocytes into the high papillary dermis. In BP patients, there are numerous mast cells at that location. IgE binds to the mast cells, which have IgE receptors on their surface, and in the presence of the BP180 antigen, forms dimers on the mast cells, and causes them to release inflammatory cytokines, some of which recruit eosinophils. This is likely why BP is such an inflammatory disorder. You cannot follow the IgE levels; you have to follow the eosinophils. The IgE is still high, but it’s nullified and inactive.”

Other biologics that have been successfully used in PV, PF, and BP include tumor necrosis factor–alpha inhibitors and rituximab (Rituxan). Common dosing for rituximab is 325 mg/m2 per week for 4 weeks. Infusion reactions are the most common side effect, he said, but other reported adverse reactions include infections, transient hypogammaglobulinemia, neutropenia, deep vein thrombosis, and pulmonary embolism. “The incidence of side effects seems to be going down, because we are now premedicating patients with antihistamines and IV hydrocortisone before giving them rituximab,” Dr. Woodley noted.

The development of progressive multifocal leukoencephalopathy has also been reported with the use of rituximab. “This is exceedingly rare with rituximab but has been described, and this is what keeps doctors who use this drug awake at night,” he said.

Elderly patients with mild BP sometimes can get by without using immunosuppressive agents to manage their disease. One option is potent topical steroids plus niacinamide 0.5-2 g after each meal as an anti-inflammatory B vitamin. “Doxycycline 100 mg b.i.d. also works to inhibit neutrophils,” he said. “Antihistamines can also be helpful, and some French dermatologists have found total body clobetasol to be useful.”

Dr. Woodley disclosed that he holds patents on human recombinant type VII collagen. He is also a consultant for Shire Pharmaceuticals and a speaker for Biofusion.

[email protected]

NEWPORT BEACH, CALIF. – Current treatment of autoimmune blistering diseases is not backed by evidence-based medicine and solid randomized, controlled trials, according to David T. Woodley, MD.

“These are rare diseases; there’s no consensus on the treatment of choice,” Dr. Woodley said at the annual meeting of the Pacific Dermatologic Association.

Dr. Woodley, professor of dermatology at the University of Southern California, Los Angeles, limited his discussion to pemphigus vulgaris (PV), pemphigus foliaceus (PF), and bullous pemphigoid (BP). The histologic hallmark of PV and PF is acantholysis. “Because these are intraepidermal blistering diseases, you don’t see the blister very often; maybe you’ll have a few intact loose sacklike blisters, but you mostly see erosions and crusting,” he said. “PV often only begins with mouth lesions.”

Dr. David T. Woodley

Work-up for a suspected autoimmune blistering disease includes a physical exam, histology, direct and indirect immunofluorescence, and serologic tests. The diagnosis should be based on the target autoantigen in the skin. PV and PF can appear identical on direct immunofluorescence, even though the blister cleavage plane is very high in PF and usually just above the basal keratinocytes in PV. “PF can have an intercellular keratinocyte cell surface staining pattern throughout the full epidermis or sometimes only the upper epidermal layers,” Dr. Woodley said.

At an international meeting on pemphigus in 2015, Dr. Woodley and his associates presented results from an ongoing study that is following 44 pemphigus patients at Keck Hospital of USC (a private university health care system) and 40 patients at Los Angeles County and USC Medical Center (a public safety net health care system). “The question we asked was, When the same doctors treat patients with a serious complicated disease requiring lots of details and follow-up at two very different health care systems, were there any differences in the outcomes of these patients?”

They found that the rates of clinical and immunologic remission were identical at both hospitals. However, at the county hospital, there was a higher incidence of relapses (59% vs. 30%). In addition, complications between the county and private hospitals differed in terms of hyperglycemia (38% vs. 11%, respectively), infections (79% vs. 37%), deaths (1 vs. none), medication dosage nonadherence (68% vs. 22%), and inappropriate discontinuation of one or more medications (68% vs. 15%). “Current research goals are to determine what factors cause medication compliance and noncompliance,” he said.

Dr. Woodley noted that one autoimmune blistering disease can evolve into another because of the phenomenon of epitope spreading. “The concept is that inflammation from one autoimmune blistering disease creates skin injury and reveals new neoautoantigens that get recognized by the patient’s immune system,” he said.

For example, a patient who had PF and high-titer autoantibodies to desmoglein 1 after a couple of years began to have blisters and erosions in her mouth, which is not supposed to happen in PF. Immunologic testing of this patient showed that in addition to antibodies against desmoglein 1, she began making high-titer autoantibodies against desmoglein 3 and had transformed into PV.

Bullous pemphigoid is another well-characterized autoimmune bullous disease that usually occurs in elderly patients. The blister is beneath the epidermis at the dermal-epidermal junction. These patients may have oral involvement. BP is characterized by tense subepidermal bullae on inflammatory bases. Histology reveals epidermal-dermal separation, many eosinophils and mast cells, and sometimes many polymorphonuclear leukocytes. “Many of these patients have very high IgE antibodies as well as IgG,” he said.

Features of BP include IgG and C3 deposits at the dermal-epidermal junction by direct immunofluorescence and by indirect immunofluorescence. “On salt-split human skin substrate, these antibodies bind to the epidermal roof of the separation and not to the dermal floor,” Dr. Woodley said. “You can send off the patient’s serum for ELISA [enzyme-linked immunosorbent assay] testing to detect autoantibodies against the BP230 antigen and the BP180 antigen to confirm the diagnosis. Autoantibodies to the BP180 antigen often correlate with the patient’s disease activity. The sensitivity of indirect immunofluorescence and ELISA are both above 95%.”

BP can present with urticarial plaques and pruritus and without blisters. Also, recent research has demonstrated that BP can present with just pruritus and no skin lesions. “So that’s something to keep in mind in refractory pruritus patients,” he said.

The incidence of BP seems to be increasing, from an estimated 7 cases per million in 1995 to 43 cases per million in 2008, Dr. Woodley said. “It may be that it is associated with some drugs like loop diuretics and spironolactone, but the precise reason is not known,” he said. “If your patient has dementia or Parkinson’s disease, he or she has a fourfold increased chance that they will have BP, because the BP180 and BP230 antigens are also in neuronal cells. Parkinson’s patients are known to make antibodies to the BP180 antigen, but not to the NC16A domain of the BP180 antigen. The development of BP in a Parkinson’s patient occurs when he or she begins to also make autoantibodies against the NC16A domain.”

 

 

The standard of treatment for autoimmune blistering diseases is prednisone 0.7-2 mg/kg. Nonsteroidal immunosuppressive agents are also helpful, including methotrexate, azathioprine, cyclophosphamide, and mycophenolate mofetil. Emerging evidence suggests that rituximab is the drug of choice for PV and PF, and should be the first-line therapy. Rituximab is a chimeric monoclonal antibody that targets CD20–positive B lymphocytes. “It removes cells that are ready to transform into autoantibody-producing short-lived plasma cells,” Dr. Woodley said. “The depletion lasts 6-12 months.”

Another new development in BP is the use of omalizumab, a monoclonal antibody to IgE. “Omalizumab inhibits the IgE antibody binding to the BP180,” Dr. Woodley said.

“It’s thought that the BP180 antigen is released from basal keratinocytes into the high papillary dermis. In BP patients, there are numerous mast cells at that location. IgE binds to the mast cells, which have IgE receptors on their surface, and in the presence of the BP180 antigen, forms dimers on the mast cells, and causes them to release inflammatory cytokines, some of which recruit eosinophils. This is likely why BP is such an inflammatory disorder. You cannot follow the IgE levels; you have to follow the eosinophils. The IgE is still high, but it’s nullified and inactive.”

Other biologics that have been successfully used in PV, PF, and BP include tumor necrosis factor–alpha inhibitors and rituximab (Rituxan). Common dosing for rituximab is 325 mg/m2 per week for 4 weeks. Infusion reactions are the most common side effect, he said, but other reported adverse reactions include infections, transient hypogammaglobulinemia, neutropenia, deep vein thrombosis, and pulmonary embolism. “The incidence of side effects seems to be going down, because we are now premedicating patients with antihistamines and IV hydrocortisone before giving them rituximab,” Dr. Woodley noted.

The development of progressive multifocal leukoencephalopathy has also been reported with the use of rituximab. “This is exceedingly rare with rituximab but has been described, and this is what keeps doctors who use this drug awake at night,” he said.

Elderly patients with mild BP sometimes can get by without using immunosuppressive agents to manage their disease. One option is potent topical steroids plus niacinamide 0.5-2 g after each meal as an anti-inflammatory B vitamin. “Doxycycline 100 mg b.i.d. also works to inhibit neutrophils,” he said. “Antihistamines can also be helpful, and some French dermatologists have found total body clobetasol to be useful.”

Dr. Woodley disclosed that he holds patents on human recombinant type VII collagen. He is also a consultant for Shire Pharmaceuticals and a speaker for Biofusion.

[email protected]

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NEWPORT BEACH, CALIF. – As the health care delivery landscape continues to evolve, expect the use of telemedicine to expand in dermatology.

“We have a robust evidence base that this is a valid way to deliver health care that can significantly improve patient access and offer comparable diagnostic and therapeutic outcomes, compared with in-person dermatology,” Ivy A. Lee, MD, said at the annual meeting of the Pacific Dermatologic Association. “This is an efficient way to improve access to our small and mighty workforce.”

Many factors are driving teledermatology’s rise in popularity, including patient access issues. “These are getting more prominent and more prevalent, not only in the uninsured and the underinsured, but also in our insured population,” said Dr. Lee, a Pasadena, Calif.–based dermatologist who also chairs the American Academy of Dermatology’s Telemedicine Task Force. “In my private practice, it’s about a 6- to 8-week wait for a new patient appointment, and this is in an affluent part of Los Angeles.”

Then there’s the increasing expectations of today’s health care consumers, who “want a better medical experience,” she said. “They don’t want to spend all their day in our waiting room, and they want to be able to get in touch with their physicians and not play phone tag with the front office staff. There’s also omnipresent technology. We have devices in our office, in our home, and in our hand – in every aspect of our lives. That’s also affecting our experience and expectations of medicine and health.”

Current forms of telemedicine range from “store and forward” (which refers to the submission of clinical images and history to a remote provider who reviews the material and sends a recommendation at a different time), “live interactive” (which uses synchronous video technology similar to FaceTime or Skype where you’re interacting with the patient or with the patient’s provider at the same time, even though you are separated by space), and “hybrid” (a combination of the two forms).

Dr. Lee said that store and forward currently is the predominant form of teledermatology “because of the convenience and ease of use. We’re a lot more efficient with that modality. We’ve used it predominantly for care delivery in a consultative practice model (provider interacts with another provider for consultation or triage of a patient). But, we also see an increasing interest and practice of direct-to-patient or direct-to-consumer care where providers interact with patients. This trend is predominantly led by telemedicine companies as a response to increasing patient demand for convenience, but also we see this practice model being adopted by larger health care systems and private practices.”

In the past, she continued, most telemedicine technology has consisted of stand-alone software platforms. The new focus is integration, asking software platforms to be more interoperable with EHRs. “Also, some EHRs are offering telemedicine capabilities,” she said. Recent interest in value-based medicine, especially since the passage of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), also plays a role in the growing adoption of telemedicine. “The focus on value and data collection is increasingly imposed upon us by multiple sources,” Dr. Lee said.

Reimbursement remains a barrier for wide adoption of teledermatology. Current models include volume-based (fee-for-service) and value-based models such as capitation, bundled payments, and pay for performance. Advances in the volume-based realm include increasing adoption of parity laws for private insurers (29 states hold such laws, which call for telemedicine services to be covered to the same extent and in a similar manner as in-person services).

In this era of higher-deductible insurance plans and narrowing networks, patients are also paying for their own care out of pocket or by using flexible savings accounts, to the tune of $30-$200 per teledermatology encounter. “We also have seen some progress with government payers in the fee-for-service models: Medicare, and less so with Medicaid,” she said. Telemedicine payments from Medicare have increased, from about $5 million in 2011 to about $18 million in 2015, but it currently reimburses live video with geographic restrictions and reimburses for store-and-forward technologies only in Alaska and Hawaii.

Medicaid “lags behind other payers,” Dr. Lee said. “Few states reimburse for store and forward, and reimbursement depends on distance requirements, eligible patient populations and health care providers, authorized technologies, and patient consent. Currently, reimbursement varies significantly across the country; it varies by state and, within each state, by payer. With the passage of MACRA, we have to start thinking about how we will practice and measure the value-based care we deliver and whether we as dermatologists will implement an alternative payment model or a merit-based incentive system. There are a lot of legislative changes in terms of getting properly paid for these services.”

 

 

On the legislative front, the Federation of State Medical Boards Interstate Medical Licensure Compact should help promote the adoption of teledermatology. This is proposed legislation to provide expedited and streamlined processes for physicians to obtain a multistate license to provide care. It’s been enacted by 17 states and proposed by 9 states and will go into effect in 2017.

“For teledermatology, this is an exciting time full of changes in practice, utilization, reimbursement, regulation, and research,” Dr. Lee concluded. “We see telemedicine increasingly integrated into mainstream medicine and health maintenance, and the outlook for dermatology is very positive.”

She reported having no relevant financial disclosures.

[email protected]

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NEWPORT BEACH, CALIF. – As the health care delivery landscape continues to evolve, expect the use of telemedicine to expand in dermatology.

“We have a robust evidence base that this is a valid way to deliver health care that can significantly improve patient access and offer comparable diagnostic and therapeutic outcomes, compared with in-person dermatology,” Ivy A. Lee, MD, said at the annual meeting of the Pacific Dermatologic Association. “This is an efficient way to improve access to our small and mighty workforce.”

Many factors are driving teledermatology’s rise in popularity, including patient access issues. “These are getting more prominent and more prevalent, not only in the uninsured and the underinsured, but also in our insured population,” said Dr. Lee, a Pasadena, Calif.–based dermatologist who also chairs the American Academy of Dermatology’s Telemedicine Task Force. “In my private practice, it’s about a 6- to 8-week wait for a new patient appointment, and this is in an affluent part of Los Angeles.”

Then there’s the increasing expectations of today’s health care consumers, who “want a better medical experience,” she said. “They don’t want to spend all their day in our waiting room, and they want to be able to get in touch with their physicians and not play phone tag with the front office staff. There’s also omnipresent technology. We have devices in our office, in our home, and in our hand – in every aspect of our lives. That’s also affecting our experience and expectations of medicine and health.”

Current forms of telemedicine range from “store and forward” (which refers to the submission of clinical images and history to a remote provider who reviews the material and sends a recommendation at a different time), “live interactive” (which uses synchronous video technology similar to FaceTime or Skype where you’re interacting with the patient or with the patient’s provider at the same time, even though you are separated by space), and “hybrid” (a combination of the two forms).

Dr. Lee said that store and forward currently is the predominant form of teledermatology “because of the convenience and ease of use. We’re a lot more efficient with that modality. We’ve used it predominantly for care delivery in a consultative practice model (provider interacts with another provider for consultation or triage of a patient). But, we also see an increasing interest and practice of direct-to-patient or direct-to-consumer care where providers interact with patients. This trend is predominantly led by telemedicine companies as a response to increasing patient demand for convenience, but also we see this practice model being adopted by larger health care systems and private practices.”

In the past, she continued, most telemedicine technology has consisted of stand-alone software platforms. The new focus is integration, asking software platforms to be more interoperable with EHRs. “Also, some EHRs are offering telemedicine capabilities,” she said. Recent interest in value-based medicine, especially since the passage of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), also plays a role in the growing adoption of telemedicine. “The focus on value and data collection is increasingly imposed upon us by multiple sources,” Dr. Lee said.

Reimbursement remains a barrier for wide adoption of teledermatology. Current models include volume-based (fee-for-service) and value-based models such as capitation, bundled payments, and pay for performance. Advances in the volume-based realm include increasing adoption of parity laws for private insurers (29 states hold such laws, which call for telemedicine services to be covered to the same extent and in a similar manner as in-person services).

In this era of higher-deductible insurance plans and narrowing networks, patients are also paying for their own care out of pocket or by using flexible savings accounts, to the tune of $30-$200 per teledermatology encounter. “We also have seen some progress with government payers in the fee-for-service models: Medicare, and less so with Medicaid,” she said. Telemedicine payments from Medicare have increased, from about $5 million in 2011 to about $18 million in 2015, but it currently reimburses live video with geographic restrictions and reimburses for store-and-forward technologies only in Alaska and Hawaii.

Medicaid “lags behind other payers,” Dr. Lee said. “Few states reimburse for store and forward, and reimbursement depends on distance requirements, eligible patient populations and health care providers, authorized technologies, and patient consent. Currently, reimbursement varies significantly across the country; it varies by state and, within each state, by payer. With the passage of MACRA, we have to start thinking about how we will practice and measure the value-based care we deliver and whether we as dermatologists will implement an alternative payment model or a merit-based incentive system. There are a lot of legislative changes in terms of getting properly paid for these services.”

 

 

On the legislative front, the Federation of State Medical Boards Interstate Medical Licensure Compact should help promote the adoption of teledermatology. This is proposed legislation to provide expedited and streamlined processes for physicians to obtain a multistate license to provide care. It’s been enacted by 17 states and proposed by 9 states and will go into effect in 2017.

“For teledermatology, this is an exciting time full of changes in practice, utilization, reimbursement, regulation, and research,” Dr. Lee concluded. “We see telemedicine increasingly integrated into mainstream medicine and health maintenance, and the outlook for dermatology is very positive.”

She reported having no relevant financial disclosures.

[email protected]

NEWPORT BEACH, CALIF. – As the health care delivery landscape continues to evolve, expect the use of telemedicine to expand in dermatology.

“We have a robust evidence base that this is a valid way to deliver health care that can significantly improve patient access and offer comparable diagnostic and therapeutic outcomes, compared with in-person dermatology,” Ivy A. Lee, MD, said at the annual meeting of the Pacific Dermatologic Association. “This is an efficient way to improve access to our small and mighty workforce.”

Many factors are driving teledermatology’s rise in popularity, including patient access issues. “These are getting more prominent and more prevalent, not only in the uninsured and the underinsured, but also in our insured population,” said Dr. Lee, a Pasadena, Calif.–based dermatologist who also chairs the American Academy of Dermatology’s Telemedicine Task Force. “In my private practice, it’s about a 6- to 8-week wait for a new patient appointment, and this is in an affluent part of Los Angeles.”

Then there’s the increasing expectations of today’s health care consumers, who “want a better medical experience,” she said. “They don’t want to spend all their day in our waiting room, and they want to be able to get in touch with their physicians and not play phone tag with the front office staff. There’s also omnipresent technology. We have devices in our office, in our home, and in our hand – in every aspect of our lives. That’s also affecting our experience and expectations of medicine and health.”

Current forms of telemedicine range from “store and forward” (which refers to the submission of clinical images and history to a remote provider who reviews the material and sends a recommendation at a different time), “live interactive” (which uses synchronous video technology similar to FaceTime or Skype where you’re interacting with the patient or with the patient’s provider at the same time, even though you are separated by space), and “hybrid” (a combination of the two forms).

Dr. Lee said that store and forward currently is the predominant form of teledermatology “because of the convenience and ease of use. We’re a lot more efficient with that modality. We’ve used it predominantly for care delivery in a consultative practice model (provider interacts with another provider for consultation or triage of a patient). But, we also see an increasing interest and practice of direct-to-patient or direct-to-consumer care where providers interact with patients. This trend is predominantly led by telemedicine companies as a response to increasing patient demand for convenience, but also we see this practice model being adopted by larger health care systems and private practices.”

In the past, she continued, most telemedicine technology has consisted of stand-alone software platforms. The new focus is integration, asking software platforms to be more interoperable with EHRs. “Also, some EHRs are offering telemedicine capabilities,” she said. Recent interest in value-based medicine, especially since the passage of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), also plays a role in the growing adoption of telemedicine. “The focus on value and data collection is increasingly imposed upon us by multiple sources,” Dr. Lee said.

Reimbursement remains a barrier for wide adoption of teledermatology. Current models include volume-based (fee-for-service) and value-based models such as capitation, bundled payments, and pay for performance. Advances in the volume-based realm include increasing adoption of parity laws for private insurers (29 states hold such laws, which call for telemedicine services to be covered to the same extent and in a similar manner as in-person services).

In this era of higher-deductible insurance plans and narrowing networks, patients are also paying for their own care out of pocket or by using flexible savings accounts, to the tune of $30-$200 per teledermatology encounter. “We also have seen some progress with government payers in the fee-for-service models: Medicare, and less so with Medicaid,” she said. Telemedicine payments from Medicare have increased, from about $5 million in 2011 to about $18 million in 2015, but it currently reimburses live video with geographic restrictions and reimburses for store-and-forward technologies only in Alaska and Hawaii.

Medicaid “lags behind other payers,” Dr. Lee said. “Few states reimburse for store and forward, and reimbursement depends on distance requirements, eligible patient populations and health care providers, authorized technologies, and patient consent. Currently, reimbursement varies significantly across the country; it varies by state and, within each state, by payer. With the passage of MACRA, we have to start thinking about how we will practice and measure the value-based care we deliver and whether we as dermatologists will implement an alternative payment model or a merit-based incentive system. There are a lot of legislative changes in terms of getting properly paid for these services.”

 

 

On the legislative front, the Federation of State Medical Boards Interstate Medical Licensure Compact should help promote the adoption of teledermatology. This is proposed legislation to provide expedited and streamlined processes for physicians to obtain a multistate license to provide care. It’s been enacted by 17 states and proposed by 9 states and will go into effect in 2017.

“For teledermatology, this is an exciting time full of changes in practice, utilization, reimbursement, regulation, and research,” Dr. Lee concluded. “We see telemedicine increasingly integrated into mainstream medicine and health maintenance, and the outlook for dermatology is very positive.”

She reported having no relevant financial disclosures.

[email protected]

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Here are 5 articles in the August issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Women With BRCA1 Mutations at Higher Risk for Endometrial Cancers

To take the posttest, go to: http://bit.ly/2t6SPIY
Expires June 30, 2017

VITALSKey clinical point: Clinicians may wish to discuss the option of hysterectomy at the time of salpingo-oophorectomy in women with deleterious BRCA1 mutations.
Major finding: Among women with BRCA1 but not BRCA2 mutations there was increased risk for serous/serous-like endometrial carcinomas.
Data source: Prospective multicenter follow-up study of 1,083 women with BRCA mutations who underwent salpingo-oophorectomy without hysterectomy.
Disclosures: The study was supported by grants from the Department of Defense, National Institutes of Health, and public and private foundations. Coauthor Robert Soslow, MD, disclosed consulting for EMD Serono. No others reported conflicts of interest. The editorialists reported no conflicts of interest related to the study.

2. Cochrane Review: Topical Steroid—Vitamin D Combo Best for Scalp Psoriasis

To take the posttest, go to: http://bit.ly/2sIyLNI
Expires July 14, 2017

VITALSKey clinical point: The combination of a topical steroid and topical vitamin D is marginally better but with a similar safety profile to steroids alone as a treatment for psoriasis on the scalp.
Major finding: The combination of a topical steroid and vitamin D showed a small but statistically significant advantage over steroids alone, and a greater advantage over vitamin D alone.
Data source: A systematic review of 59 randomized controlled studies in 11,561 patients.
Disclosures: The study was supported by the Universidade Federal de São Paulo, Brazil; the Universidade Federal do Rio Grande do Norte, Brazil; and the National Institute for Health Research, United Kingdom. Six authors and one clinical referee declared speakers' fees, research grants, and funding from the pharmaceutical industry. One author had no conflicts of interest to disclose.

3. Study Finds Emergence of Azithromycin-resistant Gonorrhea

To take the posttest, go to: http://bit.ly/2u1nMmb
Expires July 16, 2017

VITALSKey clinical point:Resistance to azithromycin is emerging among patients diagnosed with gonorrhea.
Major finding: Among patients with gonorrhea, resistance to azithromycin increased from 0.6% in 2013 to 2.5% in 2014, predominantly in the Midwest.
Data source: An analysis of 5,093 Neisseria gonorrhoeae isolates from 27 clinics as part of the CDC's Gonococcal Isolate Surveillance Project.
Disclosures: The researchers had no financial disclosures.

4. Statins Improve Ovarian Cancer Survival

To take the posttest, go to: http://bit.ly/2t6swCF
Expires June 16, 2017

VITALSKey clinical point: The risk of all-cause mortality in ovarian cancer patients on statin therapy was reduced by one-third.
Major finding: Mean survival in a large cohort of women with stage III ovarian cancer was 5.8 months longer among those on statin therapy.
Data source: A retrospective study of 1,510 women diagnosed with epithelial ovarian cancer during 2007-2009.
Disclosures: Dr. Vogel reported having no financial conflicts regarding this study, conducted without commercial support.

5. Common Surgeries Linked to Chronic Opioid Use Among Opioid-naive Patients

To take the posttest, go to: http://bit.ly/2ub9fFg
Expires June 18, 2017

VITALSKey clinical point: Common surgeries increase the risk of chronic opioid use in opioid-naive adults, especially among those using antidepressants or benzodiazepines before their operations, and those with substance abuse histories.
Major finding: After adjustment for potential confounders, knee replacement increased the risk fivefold; open cholecystectomy almost fourfold; and total hip replacement and simple mastectomy almost threefold.
Data source: Insurance claims of more than 18 million people.
Disclosures: The authors had no disclosures. The work was funded in part by the Foundation for Anesthesia Education and Research and the Anesthesia Quality Institute. Claims data came from MarketScan (Truven Health Analytics).

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Here are 5 articles in the August issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Women With BRCA1 Mutations at Higher Risk for Endometrial Cancers

To take the posttest, go to: http://bit.ly/2t6SPIY
Expires June 30, 2017

VITALSKey clinical point: Clinicians may wish to discuss the option of hysterectomy at the time of salpingo-oophorectomy in women with deleterious BRCA1 mutations.
Major finding: Among women with BRCA1 but not BRCA2 mutations there was increased risk for serous/serous-like endometrial carcinomas.
Data source: Prospective multicenter follow-up study of 1,083 women with BRCA mutations who underwent salpingo-oophorectomy without hysterectomy.
Disclosures: The study was supported by grants from the Department of Defense, National Institutes of Health, and public and private foundations. Coauthor Robert Soslow, MD, disclosed consulting for EMD Serono. No others reported conflicts of interest. The editorialists reported no conflicts of interest related to the study.

2. Cochrane Review: Topical Steroid—Vitamin D Combo Best for Scalp Psoriasis

To take the posttest, go to: http://bit.ly/2sIyLNI
Expires July 14, 2017

VITALSKey clinical point: The combination of a topical steroid and topical vitamin D is marginally better but with a similar safety profile to steroids alone as a treatment for psoriasis on the scalp.
Major finding: The combination of a topical steroid and vitamin D showed a small but statistically significant advantage over steroids alone, and a greater advantage over vitamin D alone.
Data source: A systematic review of 59 randomized controlled studies in 11,561 patients.
Disclosures: The study was supported by the Universidade Federal de São Paulo, Brazil; the Universidade Federal do Rio Grande do Norte, Brazil; and the National Institute for Health Research, United Kingdom. Six authors and one clinical referee declared speakers' fees, research grants, and funding from the pharmaceutical industry. One author had no conflicts of interest to disclose.

3. Study Finds Emergence of Azithromycin-resistant Gonorrhea

To take the posttest, go to: http://bit.ly/2u1nMmb
Expires July 16, 2017

VITALSKey clinical point:Resistance to azithromycin is emerging among patients diagnosed with gonorrhea.
Major finding: Among patients with gonorrhea, resistance to azithromycin increased from 0.6% in 2013 to 2.5% in 2014, predominantly in the Midwest.
Data source: An analysis of 5,093 Neisseria gonorrhoeae isolates from 27 clinics as part of the CDC's Gonococcal Isolate Surveillance Project.
Disclosures: The researchers had no financial disclosures.

4. Statins Improve Ovarian Cancer Survival

To take the posttest, go to: http://bit.ly/2t6swCF
Expires June 16, 2017

VITALSKey clinical point: The risk of all-cause mortality in ovarian cancer patients on statin therapy was reduced by one-third.
Major finding: Mean survival in a large cohort of women with stage III ovarian cancer was 5.8 months longer among those on statin therapy.
Data source: A retrospective study of 1,510 women diagnosed with epithelial ovarian cancer during 2007-2009.
Disclosures: Dr. Vogel reported having no financial conflicts regarding this study, conducted without commercial support.

5. Common Surgeries Linked to Chronic Opioid Use Among Opioid-naive Patients

To take the posttest, go to: http://bit.ly/2ub9fFg
Expires June 18, 2017

VITALSKey clinical point: Common surgeries increase the risk of chronic opioid use in opioid-naive adults, especially among those using antidepressants or benzodiazepines before their operations, and those with substance abuse histories.
Major finding: After adjustment for potential confounders, knee replacement increased the risk fivefold; open cholecystectomy almost fourfold; and total hip replacement and simple mastectomy almost threefold.
Data source: Insurance claims of more than 18 million people.
Disclosures: The authors had no disclosures. The work was funded in part by the Foundation for Anesthesia Education and Research and the Anesthesia Quality Institute. Claims data came from MarketScan (Truven Health Analytics).

Here are 5 articles in the August issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Women With BRCA1 Mutations at Higher Risk for Endometrial Cancers

To take the posttest, go to: http://bit.ly/2t6SPIY
Expires June 30, 2017

VITALSKey clinical point: Clinicians may wish to discuss the option of hysterectomy at the time of salpingo-oophorectomy in women with deleterious BRCA1 mutations.
Major finding: Among women with BRCA1 but not BRCA2 mutations there was increased risk for serous/serous-like endometrial carcinomas.
Data source: Prospective multicenter follow-up study of 1,083 women with BRCA mutations who underwent salpingo-oophorectomy without hysterectomy.
Disclosures: The study was supported by grants from the Department of Defense, National Institutes of Health, and public and private foundations. Coauthor Robert Soslow, MD, disclosed consulting for EMD Serono. No others reported conflicts of interest. The editorialists reported no conflicts of interest related to the study.

2. Cochrane Review: Topical Steroid—Vitamin D Combo Best for Scalp Psoriasis

To take the posttest, go to: http://bit.ly/2sIyLNI
Expires July 14, 2017

VITALSKey clinical point: The combination of a topical steroid and topical vitamin D is marginally better but with a similar safety profile to steroids alone as a treatment for psoriasis on the scalp.
Major finding: The combination of a topical steroid and vitamin D showed a small but statistically significant advantage over steroids alone, and a greater advantage over vitamin D alone.
Data source: A systematic review of 59 randomized controlled studies in 11,561 patients.
Disclosures: The study was supported by the Universidade Federal de São Paulo, Brazil; the Universidade Federal do Rio Grande do Norte, Brazil; and the National Institute for Health Research, United Kingdom. Six authors and one clinical referee declared speakers' fees, research grants, and funding from the pharmaceutical industry. One author had no conflicts of interest to disclose.

3. Study Finds Emergence of Azithromycin-resistant Gonorrhea

To take the posttest, go to: http://bit.ly/2u1nMmb
Expires July 16, 2017

VITALSKey clinical point:Resistance to azithromycin is emerging among patients diagnosed with gonorrhea.
Major finding: Among patients with gonorrhea, resistance to azithromycin increased from 0.6% in 2013 to 2.5% in 2014, predominantly in the Midwest.
Data source: An analysis of 5,093 Neisseria gonorrhoeae isolates from 27 clinics as part of the CDC's Gonococcal Isolate Surveillance Project.
Disclosures: The researchers had no financial disclosures.

4. Statins Improve Ovarian Cancer Survival

To take the posttest, go to: http://bit.ly/2t6swCF
Expires June 16, 2017

VITALSKey clinical point: The risk of all-cause mortality in ovarian cancer patients on statin therapy was reduced by one-third.
Major finding: Mean survival in a large cohort of women with stage III ovarian cancer was 5.8 months longer among those on statin therapy.
Data source: A retrospective study of 1,510 women diagnosed with epithelial ovarian cancer during 2007-2009.
Disclosures: Dr. Vogel reported having no financial conflicts regarding this study, conducted without commercial support.

5. Common Surgeries Linked to Chronic Opioid Use Among Opioid-naive Patients

To take the posttest, go to: http://bit.ly/2ub9fFg
Expires June 18, 2017

VITALSKey clinical point: Common surgeries increase the risk of chronic opioid use in opioid-naive adults, especially among those using antidepressants or benzodiazepines before their operations, and those with substance abuse histories.
Major finding: After adjustment for potential confounders, knee replacement increased the risk fivefold; open cholecystectomy almost fourfold; and total hip replacement and simple mastectomy almost threefold.
Data source: Insurance claims of more than 18 million people.
Disclosures: The authors had no disclosures. The work was funded in part by the Foundation for Anesthesia Education and Research and the Anesthesia Quality Institute. Claims data came from MarketScan (Truven Health Analytics).

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Drugs in the pipeline hold promise for atopic dermatitis

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NEWPORT BEACH, CALIF. – In the clinical opinion of Kelly M. Cordoro, MD, anyone who cares for patients with severe atopic dermatitis understands the sense of misery that can ensue.

“Atopic dermatitis patients don’t sleep well; they have poor school and work performance,” she said at the annual meeting of the Pacific Dermatologic Association. “They have absences. They’re unable to play; they can’t exercise. This leads to social disability; isolation from peers, and it goes on and on. The patients are miserable, the whole family is miserable, and we as physicians trying to sort out how to optimally treat them are miserable trying to figure out what the next best step is.”

Dr. Kelly M. Cordoro

The good news is, several drugs in the pipeline hold promise for atopic dermatitis patients, thanks largely to emerging data on its pathophysiology. In addition, mechanisms of itch, which are not yet fully understood, are also being unraveled. “It’s exciting to read the literature about the interaction of the skin, the immune system, and the nervous system,” said Dr. Cordoro, a pediatric dermatologist at the University of California, San Francisco. “Many of the mediators of itch are being identified. That has allowed for the development of targeted therapies against many of them.”

One of the promising treatments on the horizon for atopic dermatitis patients is phosphodiesterase-4 (PDE4) inhibitors. PDE-4 is a predominant cAMP-degrading enzyme in keratinocytes and inflammatory cells. “It’s really a candidate for not only atopic dermatitis but for psoriasis,” she said.

Oral PDE-4 inhibitors are already approved for psoriasis. Apremilast (Otezla) was approved by the Food and Drug Administration in 2014 for psoriasis and psoriatic arthritis, and a phase II trial of topical apremilast in adults with AD has been completed and the results are pending. “I look forward to seeing if this can help our patients,” Dr. Cordoro said.

Another promising agent for atopic dermatitis is 2% crisaborole topical ointment, a boron-based PDE-4 inhibitor developed by Anacor Pharmaceuticals. Dr. Cordoro described this compound as an anti-inflammatory agent that modifies inflammation by inhibiting the degradation of cAMP by PDE4, resulting in downstream modification of nuclear factor-kB and T-cell signaling pathways.

“Crisaborole has shown promising results from four clinical studies in patients 2 years of age and older, with notable improvements in all atopic dermatitis parameters,” she said (J Am Acad Dermatol. 2016 Sept;75[3]:494-503.e). The FDA review of crisaborole for the treatment of mild to moderate atopic dermatitis in children and adults is currently underway, and is expected to be completed by early January 2017.

An especially favorable drug in development for atopic dermatitis is dupilumab, a fully human monoclonal antibody that targets the interleukin (IL)–4 receptor, and inhibits IL-4 and IL-13 signaling. A published trial of its use in adults with moderate to severe atopic dermatitis showed rapid improvements in all atopic dermatitis clinical indices (N Engl J Med. 2014;371[2]:130-9). The most common side effects were headache and pharyngitis, and skin infections and flares were more common in the placebo group, compared with the treatment group.

Dupilumab “has the potential to shift the treatment landscape of atopic dermatitis, because it can actually change the molecular signature of dermatitic skin, reducing inflammatory and proliferative markers,” Dr. Cordoro said. There are ongoing trials in adult and pediatric populations and FDA approval is anticipated in early 2017.

Published reports also suggest a role for the IL-12/23 pathway inhibitor ustekinumab in severe refractory adult atopic dermatitis (Int J Dermatol. 2012;51[1]:115-6 and JAAD Case Reports 2015;1:25-6). Additional studies are ongoing.

Therapies for itch that have completed phase II trials include the anti-IL31R monoclonal antibody nemolizumab (CIM331); the neurokinin-1R antagonist VLY-686; and the neurokinin-1R antagonist aprepitant gel.

Dr. Cordoro disclosed that she is a consultant for Celgene Corporation, Valeant, and Anacor Pharmaceuticals.

[email protected]

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NEWPORT BEACH, CALIF. – In the clinical opinion of Kelly M. Cordoro, MD, anyone who cares for patients with severe atopic dermatitis understands the sense of misery that can ensue.

“Atopic dermatitis patients don’t sleep well; they have poor school and work performance,” she said at the annual meeting of the Pacific Dermatologic Association. “They have absences. They’re unable to play; they can’t exercise. This leads to social disability; isolation from peers, and it goes on and on. The patients are miserable, the whole family is miserable, and we as physicians trying to sort out how to optimally treat them are miserable trying to figure out what the next best step is.”

Dr. Kelly M. Cordoro

The good news is, several drugs in the pipeline hold promise for atopic dermatitis patients, thanks largely to emerging data on its pathophysiology. In addition, mechanisms of itch, which are not yet fully understood, are also being unraveled. “It’s exciting to read the literature about the interaction of the skin, the immune system, and the nervous system,” said Dr. Cordoro, a pediatric dermatologist at the University of California, San Francisco. “Many of the mediators of itch are being identified. That has allowed for the development of targeted therapies against many of them.”

One of the promising treatments on the horizon for atopic dermatitis patients is phosphodiesterase-4 (PDE4) inhibitors. PDE-4 is a predominant cAMP-degrading enzyme in keratinocytes and inflammatory cells. “It’s really a candidate for not only atopic dermatitis but for psoriasis,” she said.

Oral PDE-4 inhibitors are already approved for psoriasis. Apremilast (Otezla) was approved by the Food and Drug Administration in 2014 for psoriasis and psoriatic arthritis, and a phase II trial of topical apremilast in adults with AD has been completed and the results are pending. “I look forward to seeing if this can help our patients,” Dr. Cordoro said.

Another promising agent for atopic dermatitis is 2% crisaborole topical ointment, a boron-based PDE-4 inhibitor developed by Anacor Pharmaceuticals. Dr. Cordoro described this compound as an anti-inflammatory agent that modifies inflammation by inhibiting the degradation of cAMP by PDE4, resulting in downstream modification of nuclear factor-kB and T-cell signaling pathways.

“Crisaborole has shown promising results from four clinical studies in patients 2 years of age and older, with notable improvements in all atopic dermatitis parameters,” she said (J Am Acad Dermatol. 2016 Sept;75[3]:494-503.e). The FDA review of crisaborole for the treatment of mild to moderate atopic dermatitis in children and adults is currently underway, and is expected to be completed by early January 2017.

An especially favorable drug in development for atopic dermatitis is dupilumab, a fully human monoclonal antibody that targets the interleukin (IL)–4 receptor, and inhibits IL-4 and IL-13 signaling. A published trial of its use in adults with moderate to severe atopic dermatitis showed rapid improvements in all atopic dermatitis clinical indices (N Engl J Med. 2014;371[2]:130-9). The most common side effects were headache and pharyngitis, and skin infections and flares were more common in the placebo group, compared with the treatment group.

Dupilumab “has the potential to shift the treatment landscape of atopic dermatitis, because it can actually change the molecular signature of dermatitic skin, reducing inflammatory and proliferative markers,” Dr. Cordoro said. There are ongoing trials in adult and pediatric populations and FDA approval is anticipated in early 2017.

Published reports also suggest a role for the IL-12/23 pathway inhibitor ustekinumab in severe refractory adult atopic dermatitis (Int J Dermatol. 2012;51[1]:115-6 and JAAD Case Reports 2015;1:25-6). Additional studies are ongoing.

Therapies for itch that have completed phase II trials include the anti-IL31R monoclonal antibody nemolizumab (CIM331); the neurokinin-1R antagonist VLY-686; and the neurokinin-1R antagonist aprepitant gel.

Dr. Cordoro disclosed that she is a consultant for Celgene Corporation, Valeant, and Anacor Pharmaceuticals.

[email protected]

NEWPORT BEACH, CALIF. – In the clinical opinion of Kelly M. Cordoro, MD, anyone who cares for patients with severe atopic dermatitis understands the sense of misery that can ensue.

“Atopic dermatitis patients don’t sleep well; they have poor school and work performance,” she said at the annual meeting of the Pacific Dermatologic Association. “They have absences. They’re unable to play; they can’t exercise. This leads to social disability; isolation from peers, and it goes on and on. The patients are miserable, the whole family is miserable, and we as physicians trying to sort out how to optimally treat them are miserable trying to figure out what the next best step is.”

Dr. Kelly M. Cordoro

The good news is, several drugs in the pipeline hold promise for atopic dermatitis patients, thanks largely to emerging data on its pathophysiology. In addition, mechanisms of itch, which are not yet fully understood, are also being unraveled. “It’s exciting to read the literature about the interaction of the skin, the immune system, and the nervous system,” said Dr. Cordoro, a pediatric dermatologist at the University of California, San Francisco. “Many of the mediators of itch are being identified. That has allowed for the development of targeted therapies against many of them.”

One of the promising treatments on the horizon for atopic dermatitis patients is phosphodiesterase-4 (PDE4) inhibitors. PDE-4 is a predominant cAMP-degrading enzyme in keratinocytes and inflammatory cells. “It’s really a candidate for not only atopic dermatitis but for psoriasis,” she said.

Oral PDE-4 inhibitors are already approved for psoriasis. Apremilast (Otezla) was approved by the Food and Drug Administration in 2014 for psoriasis and psoriatic arthritis, and a phase II trial of topical apremilast in adults with AD has been completed and the results are pending. “I look forward to seeing if this can help our patients,” Dr. Cordoro said.

Another promising agent for atopic dermatitis is 2% crisaborole topical ointment, a boron-based PDE-4 inhibitor developed by Anacor Pharmaceuticals. Dr. Cordoro described this compound as an anti-inflammatory agent that modifies inflammation by inhibiting the degradation of cAMP by PDE4, resulting in downstream modification of nuclear factor-kB and T-cell signaling pathways.

“Crisaborole has shown promising results from four clinical studies in patients 2 years of age and older, with notable improvements in all atopic dermatitis parameters,” she said (J Am Acad Dermatol. 2016 Sept;75[3]:494-503.e). The FDA review of crisaborole for the treatment of mild to moderate atopic dermatitis in children and adults is currently underway, and is expected to be completed by early January 2017.

An especially favorable drug in development for atopic dermatitis is dupilumab, a fully human monoclonal antibody that targets the interleukin (IL)–4 receptor, and inhibits IL-4 and IL-13 signaling. A published trial of its use in adults with moderate to severe atopic dermatitis showed rapid improvements in all atopic dermatitis clinical indices (N Engl J Med. 2014;371[2]:130-9). The most common side effects were headache and pharyngitis, and skin infections and flares were more common in the placebo group, compared with the treatment group.

Dupilumab “has the potential to shift the treatment landscape of atopic dermatitis, because it can actually change the molecular signature of dermatitic skin, reducing inflammatory and proliferative markers,” Dr. Cordoro said. There are ongoing trials in adult and pediatric populations and FDA approval is anticipated in early 2017.

Published reports also suggest a role for the IL-12/23 pathway inhibitor ustekinumab in severe refractory adult atopic dermatitis (Int J Dermatol. 2012;51[1]:115-6 and JAAD Case Reports 2015;1:25-6). Additional studies are ongoing.

Therapies for itch that have completed phase II trials include the anti-IL31R monoclonal antibody nemolizumab (CIM331); the neurokinin-1R antagonist VLY-686; and the neurokinin-1R antagonist aprepitant gel.

Dr. Cordoro disclosed that she is a consultant for Celgene Corporation, Valeant, and Anacor Pharmaceuticals.

[email protected]

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Proper treatment of herpes zoster ‘a work in progress’

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NEWPORT BEACH, CALIF. – In medical school you may have been taught that herpes zoster infection primarily impacts elderly patients, but the burden of disease is shifting – along with the understanding of herpes zoster itself.

“Herpes zoster is a disease that can lull us into a false sense of security because we see it all the time,” Iris Ahronowitz, MD, said at the annual meeting of the Pacific Dermatologic Association. “But our understanding of how to manage this disease is still very much a work in progress.”

Dr. Iris Ahronowitz

She noted that while 50% of people will acquire herpes zoster by the time they reach 85 years of age due to diminishing cell-mediated immunity, the major burden of disease impacts immunocompromised patients of all ages. HIV patients and solid-organ transplant recipients are well known to face an increased risk of acquiring herpes zoster, but the most overwhelming risk is seen in leukemia patients, who have rates as high as 100-fold that of the general population.

“More recent data on stem cell transplant patients show that about 50% of them will get zoster,” added Dr. Ahronowitz, a dermatologist at the University of Southern California, Los Angeles. “Most of that’s happening within the first year and a half after their transplant.”

Several recent epidemiologic studies in the medical literature have reported herpes zoster in patients who are not traditionally believed to be immunosuppressed, such as those with lupus, dermatomyositis, rheumatoid arthritis, asthma, and atopic dermatitis. “It begs the question: is it the disease or is it the treatment?” Dr. Ahronowitz said. “We don’t know the answer to that yet. In dermatomyositis and lupus, use of antimalarials has been found to be most associated with the risk of herpes zoster. Other studies looking at one disease are so heterogeneous, some saying that it’s one medication, some saying that it’s another. There’s no cohesive message yet about which medications cause the highest risk of zoster.”

Herpes zoster was originally believed to be far less transmissible than varicella. “Later it was thought that the only way that you can get VZV [varicella zoster virus] from a zoster patient was by direct contact with vesicle fluid,” Dr. Ahronowitz said. “That turns out to be wrong as well.” One study of pediatric patients found similar rates of secondary varicella cases from varicella and herpes zoster cases (15% vs. 9%, respectively), regardless of anatomic location of zoster (J Infect Dis. 2012; 205[9]:1336-41).

Another report that called into question prevailing beliefs about the disease involved an immunocompetent patient in a long-term care facility who developed localized herpes zoster (J Infect Dis. 2008;197[5]:646-53). That individual turned out to be “patient zero” in a varicella outbreak in the facility, even though the person’s lesions had been covered by gauze and clothing at all times. “The next patient who got infected was one of the health care workers who had never been in the room at the same time as the patient but who had changed the patient’s bed linens,” said Dr. Ahronowitz, who was not involved with the study. “Environmental samples were collected from the patient’s room and were contaminated with VZV DNA.”

She went on to note that VZV DNA has been found in vesicle fluid, serum, peripheral blood mononuclear cells, and saliva. One randomized, controlled trial found that hydrocolloid dressings are superior to traditional gauze and paper dressings in preventing the excretion of aerosolized VZV DNA from skin lesions of patients with localized herpes zoster (J Infect Dis. 2004;189[6]:1009-12). Using hydrocolloid dressings to cover lesions “does seem to make a difference,” she said. “Because of all this new data coming out, I think it’s time to reconsider isolation precautions in all hospitalized patients with herpes zoster, because the consequences of VZV transmission within a hospital where there are other patients nearby who have low immune systems could be absolutely devastating.”

The impact of herpes zoster infection on the central nervous system can be significant, including cranial nerve palsy, encephalitis, encephalopathy, and aseptic meningitis. “Patients can have long-lasting residual neurologic deficits from this at 6 months or longer despite appropriate treatment,” she said. “No correlation between CSF viral load and neurologic sequelae has been found at 3 months.”

More recent research has found an association between herpes zoster infection and an increased risk of stroke – up to threefold in some cases. “That risk doesn’t normalize until 6 months after the infection,” Dr. Ahronowitz said. “We’re even seeing it in kids, who have two times the risk of stroke in the first 6 months after VZV infection.” MI risk also seems to be elevated as a secondary outcome (a 1.7-fold increase in the first week of infection).

 

 

“There have also been recent reports of VZV antigen/DNA found in the vessel wall of patients with giant cell arteritis and granulomatous arteritis of the aorta,” she said. “This is an evolving story about zoster that we never knew about.”

Drug-induced hypersensitivity syndrome (DIHS) is also associated with CNS manifestations, but they resolve much faster, unlike those of CNS zoster. “As long as you take away the offending medication and put them on steroids they will recover very quickly,” she said. At least one case in the medical literature to date has reported DIHS in association with VZV (Acta Derm Venereol. 2015;95[4]:503-4).

The zoster vaccine (Zostavax, Merck & Co.) is currently indicated in patients aged 60 years and older, but since it is a live attenuated vaccine, it is contraindicated in many patients who could most benefit from it, including those with primary immunodeficiency disorders, those with a hematologic malignancy, those who have had a hematopoietic stem cell transplant within the last 2 years, pregnant patients, and patients taking high-dose steroids or anti–tumor necrosis factor biologics.

“There is an inactivated vaccine in the works being tested, and that is showing good efficacy,” Dr. Ahronowitz said. “Hopefully we’ll be able to prevaccinate patients, even young patients, prior to immune suppression.”

She reported having no relevant disclosures.

[email protected]

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NEWPORT BEACH, CALIF. – In medical school you may have been taught that herpes zoster infection primarily impacts elderly patients, but the burden of disease is shifting – along with the understanding of herpes zoster itself.

“Herpes zoster is a disease that can lull us into a false sense of security because we see it all the time,” Iris Ahronowitz, MD, said at the annual meeting of the Pacific Dermatologic Association. “But our understanding of how to manage this disease is still very much a work in progress.”

Dr. Iris Ahronowitz

She noted that while 50% of people will acquire herpes zoster by the time they reach 85 years of age due to diminishing cell-mediated immunity, the major burden of disease impacts immunocompromised patients of all ages. HIV patients and solid-organ transplant recipients are well known to face an increased risk of acquiring herpes zoster, but the most overwhelming risk is seen in leukemia patients, who have rates as high as 100-fold that of the general population.

“More recent data on stem cell transplant patients show that about 50% of them will get zoster,” added Dr. Ahronowitz, a dermatologist at the University of Southern California, Los Angeles. “Most of that’s happening within the first year and a half after their transplant.”

Several recent epidemiologic studies in the medical literature have reported herpes zoster in patients who are not traditionally believed to be immunosuppressed, such as those with lupus, dermatomyositis, rheumatoid arthritis, asthma, and atopic dermatitis. “It begs the question: is it the disease or is it the treatment?” Dr. Ahronowitz said. “We don’t know the answer to that yet. In dermatomyositis and lupus, use of antimalarials has been found to be most associated with the risk of herpes zoster. Other studies looking at one disease are so heterogeneous, some saying that it’s one medication, some saying that it’s another. There’s no cohesive message yet about which medications cause the highest risk of zoster.”

Herpes zoster was originally believed to be far less transmissible than varicella. “Later it was thought that the only way that you can get VZV [varicella zoster virus] from a zoster patient was by direct contact with vesicle fluid,” Dr. Ahronowitz said. “That turns out to be wrong as well.” One study of pediatric patients found similar rates of secondary varicella cases from varicella and herpes zoster cases (15% vs. 9%, respectively), regardless of anatomic location of zoster (J Infect Dis. 2012; 205[9]:1336-41).

Another report that called into question prevailing beliefs about the disease involved an immunocompetent patient in a long-term care facility who developed localized herpes zoster (J Infect Dis. 2008;197[5]:646-53). That individual turned out to be “patient zero” in a varicella outbreak in the facility, even though the person’s lesions had been covered by gauze and clothing at all times. “The next patient who got infected was one of the health care workers who had never been in the room at the same time as the patient but who had changed the patient’s bed linens,” said Dr. Ahronowitz, who was not involved with the study. “Environmental samples were collected from the patient’s room and were contaminated with VZV DNA.”

She went on to note that VZV DNA has been found in vesicle fluid, serum, peripheral blood mononuclear cells, and saliva. One randomized, controlled trial found that hydrocolloid dressings are superior to traditional gauze and paper dressings in preventing the excretion of aerosolized VZV DNA from skin lesions of patients with localized herpes zoster (J Infect Dis. 2004;189[6]:1009-12). Using hydrocolloid dressings to cover lesions “does seem to make a difference,” she said. “Because of all this new data coming out, I think it’s time to reconsider isolation precautions in all hospitalized patients with herpes zoster, because the consequences of VZV transmission within a hospital where there are other patients nearby who have low immune systems could be absolutely devastating.”

The impact of herpes zoster infection on the central nervous system can be significant, including cranial nerve palsy, encephalitis, encephalopathy, and aseptic meningitis. “Patients can have long-lasting residual neurologic deficits from this at 6 months or longer despite appropriate treatment,” she said. “No correlation between CSF viral load and neurologic sequelae has been found at 3 months.”

More recent research has found an association between herpes zoster infection and an increased risk of stroke – up to threefold in some cases. “That risk doesn’t normalize until 6 months after the infection,” Dr. Ahronowitz said. “We’re even seeing it in kids, who have two times the risk of stroke in the first 6 months after VZV infection.” MI risk also seems to be elevated as a secondary outcome (a 1.7-fold increase in the first week of infection).

 

 

“There have also been recent reports of VZV antigen/DNA found in the vessel wall of patients with giant cell arteritis and granulomatous arteritis of the aorta,” she said. “This is an evolving story about zoster that we never knew about.”

Drug-induced hypersensitivity syndrome (DIHS) is also associated with CNS manifestations, but they resolve much faster, unlike those of CNS zoster. “As long as you take away the offending medication and put them on steroids they will recover very quickly,” she said. At least one case in the medical literature to date has reported DIHS in association with VZV (Acta Derm Venereol. 2015;95[4]:503-4).

The zoster vaccine (Zostavax, Merck & Co.) is currently indicated in patients aged 60 years and older, but since it is a live attenuated vaccine, it is contraindicated in many patients who could most benefit from it, including those with primary immunodeficiency disorders, those with a hematologic malignancy, those who have had a hematopoietic stem cell transplant within the last 2 years, pregnant patients, and patients taking high-dose steroids or anti–tumor necrosis factor biologics.

“There is an inactivated vaccine in the works being tested, and that is showing good efficacy,” Dr. Ahronowitz said. “Hopefully we’ll be able to prevaccinate patients, even young patients, prior to immune suppression.”

She reported having no relevant disclosures.

[email protected]

NEWPORT BEACH, CALIF. – In medical school you may have been taught that herpes zoster infection primarily impacts elderly patients, but the burden of disease is shifting – along with the understanding of herpes zoster itself.

“Herpes zoster is a disease that can lull us into a false sense of security because we see it all the time,” Iris Ahronowitz, MD, said at the annual meeting of the Pacific Dermatologic Association. “But our understanding of how to manage this disease is still very much a work in progress.”

Dr. Iris Ahronowitz

She noted that while 50% of people will acquire herpes zoster by the time they reach 85 years of age due to diminishing cell-mediated immunity, the major burden of disease impacts immunocompromised patients of all ages. HIV patients and solid-organ transplant recipients are well known to face an increased risk of acquiring herpes zoster, but the most overwhelming risk is seen in leukemia patients, who have rates as high as 100-fold that of the general population.

“More recent data on stem cell transplant patients show that about 50% of them will get zoster,” added Dr. Ahronowitz, a dermatologist at the University of Southern California, Los Angeles. “Most of that’s happening within the first year and a half after their transplant.”

Several recent epidemiologic studies in the medical literature have reported herpes zoster in patients who are not traditionally believed to be immunosuppressed, such as those with lupus, dermatomyositis, rheumatoid arthritis, asthma, and atopic dermatitis. “It begs the question: is it the disease or is it the treatment?” Dr. Ahronowitz said. “We don’t know the answer to that yet. In dermatomyositis and lupus, use of antimalarials has been found to be most associated with the risk of herpes zoster. Other studies looking at one disease are so heterogeneous, some saying that it’s one medication, some saying that it’s another. There’s no cohesive message yet about which medications cause the highest risk of zoster.”

Herpes zoster was originally believed to be far less transmissible than varicella. “Later it was thought that the only way that you can get VZV [varicella zoster virus] from a zoster patient was by direct contact with vesicle fluid,” Dr. Ahronowitz said. “That turns out to be wrong as well.” One study of pediatric patients found similar rates of secondary varicella cases from varicella and herpes zoster cases (15% vs. 9%, respectively), regardless of anatomic location of zoster (J Infect Dis. 2012; 205[9]:1336-41).

Another report that called into question prevailing beliefs about the disease involved an immunocompetent patient in a long-term care facility who developed localized herpes zoster (J Infect Dis. 2008;197[5]:646-53). That individual turned out to be “patient zero” in a varicella outbreak in the facility, even though the person’s lesions had been covered by gauze and clothing at all times. “The next patient who got infected was one of the health care workers who had never been in the room at the same time as the patient but who had changed the patient’s bed linens,” said Dr. Ahronowitz, who was not involved with the study. “Environmental samples were collected from the patient’s room and were contaminated with VZV DNA.”

She went on to note that VZV DNA has been found in vesicle fluid, serum, peripheral blood mononuclear cells, and saliva. One randomized, controlled trial found that hydrocolloid dressings are superior to traditional gauze and paper dressings in preventing the excretion of aerosolized VZV DNA from skin lesions of patients with localized herpes zoster (J Infect Dis. 2004;189[6]:1009-12). Using hydrocolloid dressings to cover lesions “does seem to make a difference,” she said. “Because of all this new data coming out, I think it’s time to reconsider isolation precautions in all hospitalized patients with herpes zoster, because the consequences of VZV transmission within a hospital where there are other patients nearby who have low immune systems could be absolutely devastating.”

The impact of herpes zoster infection on the central nervous system can be significant, including cranial nerve palsy, encephalitis, encephalopathy, and aseptic meningitis. “Patients can have long-lasting residual neurologic deficits from this at 6 months or longer despite appropriate treatment,” she said. “No correlation between CSF viral load and neurologic sequelae has been found at 3 months.”

More recent research has found an association between herpes zoster infection and an increased risk of stroke – up to threefold in some cases. “That risk doesn’t normalize until 6 months after the infection,” Dr. Ahronowitz said. “We’re even seeing it in kids, who have two times the risk of stroke in the first 6 months after VZV infection.” MI risk also seems to be elevated as a secondary outcome (a 1.7-fold increase in the first week of infection).

 

 

“There have also been recent reports of VZV antigen/DNA found in the vessel wall of patients with giant cell arteritis and granulomatous arteritis of the aorta,” she said. “This is an evolving story about zoster that we never knew about.”

Drug-induced hypersensitivity syndrome (DIHS) is also associated with CNS manifestations, but they resolve much faster, unlike those of CNS zoster. “As long as you take away the offending medication and put them on steroids they will recover very quickly,” she said. At least one case in the medical literature to date has reported DIHS in association with VZV (Acta Derm Venereol. 2015;95[4]:503-4).

The zoster vaccine (Zostavax, Merck & Co.) is currently indicated in patients aged 60 years and older, but since it is a live attenuated vaccine, it is contraindicated in many patients who could most benefit from it, including those with primary immunodeficiency disorders, those with a hematologic malignancy, those who have had a hematopoietic stem cell transplant within the last 2 years, pregnant patients, and patients taking high-dose steroids or anti–tumor necrosis factor biologics.

“There is an inactivated vaccine in the works being tested, and that is showing good efficacy,” Dr. Ahronowitz said. “Hopefully we’ll be able to prevaccinate patients, even young patients, prior to immune suppression.”

She reported having no relevant disclosures.

[email protected]

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NEWPORT BEACH, CALIF. – Offering photodynamic therapy is a smart move for any dermatology practice, but also it requires common sense. That starts with making sure you treat only appropriate candidates.

“They can’t be intimidated by the thought of light or looking red, and you have to go into depth ahead of time as far as managing reactions, as well as long-term expectations,” Neal Bhatia, MD, said at the annual meeting of the Pacific Dermatologic Association. That includes reviewing any oral medications they’re taking, as well as topical products they may be using on their face or scalp.

Dr. Neal Bhatia

“I like to do this treatment on Fridays so it gives patients the weekend to stay indoors for the next 48 hours, which is really what they need to optimize the response rate,” said Dr. Bhatia, director of clinical dermatology at Therapeutics Clinical Research in San Diego. “The other part of this is managing your staff. Make sure they have enough time to check in on the patients while they’re incubating away from light, as well as to review the post-treatment plan. And make sure they have a comfortable chair. Some patients might feel claustrophobic if you lay them down and put the light above them. Others might like to lay down for the procedure versus sitting down.”

His checklist for treatment day includes a reminder for patients to bring a wide-brimmed hat to shield the treated lesions from ambient light, as well as a book, computer, or paperwork to pass the time. He also advises putting together a take-home bag for patients that includes topical anesthetics, moisturizers, and sunscreen. In his clinical experience, prior to photodynamic therapy (PDT), there is no reason for patients to discontinue medications that are sensitizing in the UV spectrum such as antibiotics, diuretics, anti-hypertensives, since PDT works in the 410-417 nm range. “If you are concerned, you can hold the drugs the day before [the procedure], the day of, and maybe the day after, but that’s really all you need,” he said.

Dr. Bhatia discussed combinations with 5-fluorouracil (5-FU) before and after PDT, imiquimod plus aminolevulinic acid–PDT (ALA-PDT), and ingenol mebutate plus ALA-PDT. Antihistamines may play a role in helping to reduce the anticipated ALA-PDT response (J Invest Dermatol. 2006;126[10]:2296-301). Dr. Bhatia explained that the edema component is generated by mast cell release and can be uncoupled using selected H1-antihistamines, which can provide symptom relief without compromising efficacy. “Some studies talk about reducing erythema and edema based on the presence of mast cells and the surge of mast cells within first 48 to 72 hours,” he said. “Symptomatic relief is going to mean a lot to that patient who’s getting red, feeling itchy, and feeling swollen, but we don’t want to stop the reaction pattern and the efficacy by undoing what we’ve created as a response.”

It may seem counterintuitive, but direct tissue cooling after PDT appears to have a negative impact on perforin conversion, “to the point where it actually reduces the efficacy and treatment when you do direct tissue cooling,” Dr. Bhatia said. One study showed found significantly less resolution of actinic keratosis (AK) lesions treated with direct tissue cooling, compared with those who did not receive tissue cooling (J Photochem Photobiol B. 2011;103:1-7). In addition, there was a failure of conversion and optimization of the accumulated protoporphyrin IX when direct tissue cooling was used.

“That’s not to say a handheld fan or a fan in the room or aerating, making sure they have enough oxygen around the treatment area [isn’t useful],” Dr. Bhatia said. “I’m talking about the direct tissue cooling that we use with the pulsed laser device, or the Zimmer cooler. You get better conversion when you have a warming device, compared with contact cooling.”

Dr. Bhatia predicted that in the future, microneedle pre-treatment of human skin is going to gain popularity as a PDT adjunct. On early study of microneedling found that it improved 5-ALA and 5-MAL–induced protoporphyrin IX production for topical photodynamic therapy without increasing pain or erythema (Pharm Res. 2010;27[10]:2213-20). “I think that’s very important,” he said.

Dr. Bhatia disclosed having affiliations with Biofrontera and Dusa, the two main manufacturers of PDT in the United States.

[email protected]

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NEWPORT BEACH, CALIF. – Offering photodynamic therapy is a smart move for any dermatology practice, but also it requires common sense. That starts with making sure you treat only appropriate candidates.

“They can’t be intimidated by the thought of light or looking red, and you have to go into depth ahead of time as far as managing reactions, as well as long-term expectations,” Neal Bhatia, MD, said at the annual meeting of the Pacific Dermatologic Association. That includes reviewing any oral medications they’re taking, as well as topical products they may be using on their face or scalp.

Dr. Neal Bhatia

“I like to do this treatment on Fridays so it gives patients the weekend to stay indoors for the next 48 hours, which is really what they need to optimize the response rate,” said Dr. Bhatia, director of clinical dermatology at Therapeutics Clinical Research in San Diego. “The other part of this is managing your staff. Make sure they have enough time to check in on the patients while they’re incubating away from light, as well as to review the post-treatment plan. And make sure they have a comfortable chair. Some patients might feel claustrophobic if you lay them down and put the light above them. Others might like to lay down for the procedure versus sitting down.”

His checklist for treatment day includes a reminder for patients to bring a wide-brimmed hat to shield the treated lesions from ambient light, as well as a book, computer, or paperwork to pass the time. He also advises putting together a take-home bag for patients that includes topical anesthetics, moisturizers, and sunscreen. In his clinical experience, prior to photodynamic therapy (PDT), there is no reason for patients to discontinue medications that are sensitizing in the UV spectrum such as antibiotics, diuretics, anti-hypertensives, since PDT works in the 410-417 nm range. “If you are concerned, you can hold the drugs the day before [the procedure], the day of, and maybe the day after, but that’s really all you need,” he said.

Dr. Bhatia discussed combinations with 5-fluorouracil (5-FU) before and after PDT, imiquimod plus aminolevulinic acid–PDT (ALA-PDT), and ingenol mebutate plus ALA-PDT. Antihistamines may play a role in helping to reduce the anticipated ALA-PDT response (J Invest Dermatol. 2006;126[10]:2296-301). Dr. Bhatia explained that the edema component is generated by mast cell release and can be uncoupled using selected H1-antihistamines, which can provide symptom relief without compromising efficacy. “Some studies talk about reducing erythema and edema based on the presence of mast cells and the surge of mast cells within first 48 to 72 hours,” he said. “Symptomatic relief is going to mean a lot to that patient who’s getting red, feeling itchy, and feeling swollen, but we don’t want to stop the reaction pattern and the efficacy by undoing what we’ve created as a response.”

It may seem counterintuitive, but direct tissue cooling after PDT appears to have a negative impact on perforin conversion, “to the point where it actually reduces the efficacy and treatment when you do direct tissue cooling,” Dr. Bhatia said. One study showed found significantly less resolution of actinic keratosis (AK) lesions treated with direct tissue cooling, compared with those who did not receive tissue cooling (J Photochem Photobiol B. 2011;103:1-7). In addition, there was a failure of conversion and optimization of the accumulated protoporphyrin IX when direct tissue cooling was used.

“That’s not to say a handheld fan or a fan in the room or aerating, making sure they have enough oxygen around the treatment area [isn’t useful],” Dr. Bhatia said. “I’m talking about the direct tissue cooling that we use with the pulsed laser device, or the Zimmer cooler. You get better conversion when you have a warming device, compared with contact cooling.”

Dr. Bhatia predicted that in the future, microneedle pre-treatment of human skin is going to gain popularity as a PDT adjunct. On early study of microneedling found that it improved 5-ALA and 5-MAL–induced protoporphyrin IX production for topical photodynamic therapy without increasing pain or erythema (Pharm Res. 2010;27[10]:2213-20). “I think that’s very important,” he said.

Dr. Bhatia disclosed having affiliations with Biofrontera and Dusa, the two main manufacturers of PDT in the United States.

[email protected]

NEWPORT BEACH, CALIF. – Offering photodynamic therapy is a smart move for any dermatology practice, but also it requires common sense. That starts with making sure you treat only appropriate candidates.

“They can’t be intimidated by the thought of light or looking red, and you have to go into depth ahead of time as far as managing reactions, as well as long-term expectations,” Neal Bhatia, MD, said at the annual meeting of the Pacific Dermatologic Association. That includes reviewing any oral medications they’re taking, as well as topical products they may be using on their face or scalp.

Dr. Neal Bhatia

“I like to do this treatment on Fridays so it gives patients the weekend to stay indoors for the next 48 hours, which is really what they need to optimize the response rate,” said Dr. Bhatia, director of clinical dermatology at Therapeutics Clinical Research in San Diego. “The other part of this is managing your staff. Make sure they have enough time to check in on the patients while they’re incubating away from light, as well as to review the post-treatment plan. And make sure they have a comfortable chair. Some patients might feel claustrophobic if you lay them down and put the light above them. Others might like to lay down for the procedure versus sitting down.”

His checklist for treatment day includes a reminder for patients to bring a wide-brimmed hat to shield the treated lesions from ambient light, as well as a book, computer, or paperwork to pass the time. He also advises putting together a take-home bag for patients that includes topical anesthetics, moisturizers, and sunscreen. In his clinical experience, prior to photodynamic therapy (PDT), there is no reason for patients to discontinue medications that are sensitizing in the UV spectrum such as antibiotics, diuretics, anti-hypertensives, since PDT works in the 410-417 nm range. “If you are concerned, you can hold the drugs the day before [the procedure], the day of, and maybe the day after, but that’s really all you need,” he said.

Dr. Bhatia discussed combinations with 5-fluorouracil (5-FU) before and after PDT, imiquimod plus aminolevulinic acid–PDT (ALA-PDT), and ingenol mebutate plus ALA-PDT. Antihistamines may play a role in helping to reduce the anticipated ALA-PDT response (J Invest Dermatol. 2006;126[10]:2296-301). Dr. Bhatia explained that the edema component is generated by mast cell release and can be uncoupled using selected H1-antihistamines, which can provide symptom relief without compromising efficacy. “Some studies talk about reducing erythema and edema based on the presence of mast cells and the surge of mast cells within first 48 to 72 hours,” he said. “Symptomatic relief is going to mean a lot to that patient who’s getting red, feeling itchy, and feeling swollen, but we don’t want to stop the reaction pattern and the efficacy by undoing what we’ve created as a response.”

It may seem counterintuitive, but direct tissue cooling after PDT appears to have a negative impact on perforin conversion, “to the point where it actually reduces the efficacy and treatment when you do direct tissue cooling,” Dr. Bhatia said. One study showed found significantly less resolution of actinic keratosis (AK) lesions treated with direct tissue cooling, compared with those who did not receive tissue cooling (J Photochem Photobiol B. 2011;103:1-7). In addition, there was a failure of conversion and optimization of the accumulated protoporphyrin IX when direct tissue cooling was used.

“That’s not to say a handheld fan or a fan in the room or aerating, making sure they have enough oxygen around the treatment area [isn’t useful],” Dr. Bhatia said. “I’m talking about the direct tissue cooling that we use with the pulsed laser device, or the Zimmer cooler. You get better conversion when you have a warming device, compared with contact cooling.”

Dr. Bhatia predicted that in the future, microneedle pre-treatment of human skin is going to gain popularity as a PDT adjunct. On early study of microneedling found that it improved 5-ALA and 5-MAL–induced protoporphyrin IX production for topical photodynamic therapy without increasing pain or erythema (Pharm Res. 2010;27[10]:2213-20). “I think that’s very important,” he said.

Dr. Bhatia disclosed having affiliations with Biofrontera and Dusa, the two main manufacturers of PDT in the United States.

[email protected]

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Expert shares new insights on the pathophysiology of rosacea

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NEWPORT BEACH, CALIF. – In the clinical opinion of Richard L. Gallo, MD, PhD, current nomenclature for the diagnosis of rosacea could use a makeover.

“Currently, we’re still operating with an almost 20-year-old set of diagnostic subtypes of rosacea,” Dr. Gallo said at the annual meeting of the Pacific Dermatologic Association. He plans to participate in consensus meeting of experts who will convene this fall in an effort to update and modify these diagnostic criteria.

 

Dr. Richard L. Gallo

According to current nomenclature, subtype 1 is erythematotelangiectatic rosacea characterized by facial redness; subtype 2 is papulopustular, marked by bumps and pimples; subtype 3 is phymatous, characterized by enlargement of the nose, and subtype 4 is ocular, marked by eye irritation. Dr. Gallo pointed out that it’s rare to see just one of these subtypes in rosacea patients, with the exception of the erythematotelangiectatic rosacea (ETR). “There is a large population with ETR alone,” he said.” Most patients with the papulopustular subtype have aspects of ETR. There is a mix of subtypes of rosacea and we clearly need to modify our diagnostic criteria.”

 

Secondary rosacea features may include burning or stinging, plaque, dry appearance and scale, edema, ocular manifestations, peripheral location, and phymatous changes. Work by several researchers in recent years has shed light on the pathophysiology of rosacea. “We’re learning that there are many aspects to this disease that both trigger it and result in progression of the disease,” said Dr. Gallo, professor and chair of the department of dermatology at the University of California, San Diego. “It seems to have biological triggers that exist both in the environment and initiate from internal sources. We’re understanding more about the nature of those, at least specific molecules externally from microbes and so forth. Internally we understand more about the unique inflammatory signals.”

For example, he and other researchers began to look at the innate immune system patients with rosacea and identified LL37, a multifunction peptide that plays a role in a number of skin diseases, as something that can promote inflammation (Nat Med. 2007;13[8]:975-80). “It also promotes the vascular changes [that occur with the disease],” Dr. Gallo said. “We’re now learning how a dysregulation of enzymes in the skin contributes to making too much of these types of peptides. Therefore, treatment approaches that might modify enzymatic activity become useful.” Researchers have also discovered that some of the innate recognition molecules like toll-like receptor 2 (TLR2) are overexpressed in rosacea patients. “Similarly, in terms of the vascular signals, a number of labs are identifying some of the newer vascular transmitters that seem to be uniquely elevated in rosacea, so there’s great reason to be optimistic that given the increased specificity and understanding of what uniquely makes this disease happen, we’ll be able to target it in a safe way.”

A number of published studies have supported these notions, including an analysis of 275 twin pairs (JAMA Dermatol. 2015;151[11]:1213-9). The researchers found that compared with fraternal twins, identical twins had a higher association of National Rosacea Society scores (P = .04), “supporting the concept that there are fundamental genetic factors that are influencing disease,” Dr. Gallo said. Environmental factors found to be associated with rosacea include lifetime UV exposure, smoking, obesity, and alcohol use.

In an assessment of the genetic basis of rosacea by genome-wide association study, researchers identified one confirmed single-nucleotide polymorphism that could be associated with rosacea (J Invest Dermatol. 2015;135[6]:1548-55). It was located in an intergenic region between HLA-DRA and BTNL2, “which is consistent with the overall concept that there is perhaps a genetic abnormality that is leading to increased amino modulation of difficulties,” Dr. Gallo said. For another recent study, researchers analyzed 14 randomized or case control trials involving rosacea patients (Int J Med Sci. 2015;12[5]:387-96). They concluded that vasculature, chronic inflammatory responses, environmental triggers, food and chemicals ingested, and microorganisms either alone or in combination are responsible for rosacea.

Dr. Gallo went on to highlight findings from several studies that link rosacea to an increased risk for certain comorbidities. One, a nationwide case-control study from Taiwan that comprised 35,553 rosacea patients, found that the disease was significantly associated with a risk of certain cardiovascular comorbidities (J Acad Dermatol. 2015;73:249-54). These included dyslipidemia (OR 1.41), coronary artery disease (OR 1.35), and hypertension (OR 1.17). A separate analysis, based 93,314 participants in the Nurse’s Health Study, found that rosacea was significantly associated with a risk of coronary artery disease (OR 2.2). The researchers also observed that comorbidities seemed to increase with duration of the disease (Clin Gastroenterol Hepatol. 2016;14[2]:220-5). Another smaller case-control study of 65 patients and 65 controls found an increased risk with rosacea for coronary artery disease, hyperlipidemia, hypertension, and gastroesophageal reflux disease (J Am Acad Dermatol. 2015;73[4]:604-8).

 

 

A recent analysis of 75,088 participants in the Nurses’ Health Study found that women with rosacea faced an increased risk of thyroid cancer (HR 1.59) and basal cell carcinoma (HR 1.50; Br J Cancer 2015;113[3]:520-3). Rosacea may also impact one’s risk for developing certain neurological conditions. One study found an increased risk for dementia (HR 1.42) and Alzheimer’s disease (HR 1.92; Ann Neurol. 2016;79:921-8), while another found an increased risk for Parkinson’s disease (an adjusted incident ratio of 1.71 in patients with rosacea, compared with the referent population; JAMA Neurol. 2016;73[5]:529-34).

As for therapy, a recent Cochrane systematic review found strong evidence supporting benefits of several therapies over placebo, including metronidazole, azelaic acid, brimonidine, tetracycline, doxycycline 40 mg, ivermectin, and isotretinoin (Br J Dermatol. 2015;173[3]:651-2). A separate, 7-year retrospective study of 275 adults with rosacea published online in The Journal of Dermatology on Oct. 28, 2015, found that patients with the PPR subtype had a better overall prognosis, compared with their counterparts with the other subtypes. Overall, the median time to complete remission was 56 months. Complete remission was achieved in 46% of those with PPR subtype, compared with 19% of those with mixed subtype and 11% of those with ETR subtype.

Dr. Gallo disclosed that he has received research grants from the National Institutes of Health, Allergan, L’Oreal, Colgate-Palmolive, Regeneron, GSK, Galderma, and Bayer. He is a consultant for Allergan, Colgate-Palmolive, Sente, Matrisys, Dermata, Alnylam, Abbvie, Roche, and Promius.

[email protected]

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NEWPORT BEACH, CALIF. – In the clinical opinion of Richard L. Gallo, MD, PhD, current nomenclature for the diagnosis of rosacea could use a makeover.

“Currently, we’re still operating with an almost 20-year-old set of diagnostic subtypes of rosacea,” Dr. Gallo said at the annual meeting of the Pacific Dermatologic Association. He plans to participate in consensus meeting of experts who will convene this fall in an effort to update and modify these diagnostic criteria.

 

Dr. Richard L. Gallo

According to current nomenclature, subtype 1 is erythematotelangiectatic rosacea characterized by facial redness; subtype 2 is papulopustular, marked by bumps and pimples; subtype 3 is phymatous, characterized by enlargement of the nose, and subtype 4 is ocular, marked by eye irritation. Dr. Gallo pointed out that it’s rare to see just one of these subtypes in rosacea patients, with the exception of the erythematotelangiectatic rosacea (ETR). “There is a large population with ETR alone,” he said.” Most patients with the papulopustular subtype have aspects of ETR. There is a mix of subtypes of rosacea and we clearly need to modify our diagnostic criteria.”

 

Secondary rosacea features may include burning or stinging, plaque, dry appearance and scale, edema, ocular manifestations, peripheral location, and phymatous changes. Work by several researchers in recent years has shed light on the pathophysiology of rosacea. “We’re learning that there are many aspects to this disease that both trigger it and result in progression of the disease,” said Dr. Gallo, professor and chair of the department of dermatology at the University of California, San Diego. “It seems to have biological triggers that exist both in the environment and initiate from internal sources. We’re understanding more about the nature of those, at least specific molecules externally from microbes and so forth. Internally we understand more about the unique inflammatory signals.”

For example, he and other researchers began to look at the innate immune system patients with rosacea and identified LL37, a multifunction peptide that plays a role in a number of skin diseases, as something that can promote inflammation (Nat Med. 2007;13[8]:975-80). “It also promotes the vascular changes [that occur with the disease],” Dr. Gallo said. “We’re now learning how a dysregulation of enzymes in the skin contributes to making too much of these types of peptides. Therefore, treatment approaches that might modify enzymatic activity become useful.” Researchers have also discovered that some of the innate recognition molecules like toll-like receptor 2 (TLR2) are overexpressed in rosacea patients. “Similarly, in terms of the vascular signals, a number of labs are identifying some of the newer vascular transmitters that seem to be uniquely elevated in rosacea, so there’s great reason to be optimistic that given the increased specificity and understanding of what uniquely makes this disease happen, we’ll be able to target it in a safe way.”

A number of published studies have supported these notions, including an analysis of 275 twin pairs (JAMA Dermatol. 2015;151[11]:1213-9). The researchers found that compared with fraternal twins, identical twins had a higher association of National Rosacea Society scores (P = .04), “supporting the concept that there are fundamental genetic factors that are influencing disease,” Dr. Gallo said. Environmental factors found to be associated with rosacea include lifetime UV exposure, smoking, obesity, and alcohol use.

In an assessment of the genetic basis of rosacea by genome-wide association study, researchers identified one confirmed single-nucleotide polymorphism that could be associated with rosacea (J Invest Dermatol. 2015;135[6]:1548-55). It was located in an intergenic region between HLA-DRA and BTNL2, “which is consistent with the overall concept that there is perhaps a genetic abnormality that is leading to increased amino modulation of difficulties,” Dr. Gallo said. For another recent study, researchers analyzed 14 randomized or case control trials involving rosacea patients (Int J Med Sci. 2015;12[5]:387-96). They concluded that vasculature, chronic inflammatory responses, environmental triggers, food and chemicals ingested, and microorganisms either alone or in combination are responsible for rosacea.

Dr. Gallo went on to highlight findings from several studies that link rosacea to an increased risk for certain comorbidities. One, a nationwide case-control study from Taiwan that comprised 35,553 rosacea patients, found that the disease was significantly associated with a risk of certain cardiovascular comorbidities (J Acad Dermatol. 2015;73:249-54). These included dyslipidemia (OR 1.41), coronary artery disease (OR 1.35), and hypertension (OR 1.17). A separate analysis, based 93,314 participants in the Nurse’s Health Study, found that rosacea was significantly associated with a risk of coronary artery disease (OR 2.2). The researchers also observed that comorbidities seemed to increase with duration of the disease (Clin Gastroenterol Hepatol. 2016;14[2]:220-5). Another smaller case-control study of 65 patients and 65 controls found an increased risk with rosacea for coronary artery disease, hyperlipidemia, hypertension, and gastroesophageal reflux disease (J Am Acad Dermatol. 2015;73[4]:604-8).

 

 

A recent analysis of 75,088 participants in the Nurses’ Health Study found that women with rosacea faced an increased risk of thyroid cancer (HR 1.59) and basal cell carcinoma (HR 1.50; Br J Cancer 2015;113[3]:520-3). Rosacea may also impact one’s risk for developing certain neurological conditions. One study found an increased risk for dementia (HR 1.42) and Alzheimer’s disease (HR 1.92; Ann Neurol. 2016;79:921-8), while another found an increased risk for Parkinson’s disease (an adjusted incident ratio of 1.71 in patients with rosacea, compared with the referent population; JAMA Neurol. 2016;73[5]:529-34).

As for therapy, a recent Cochrane systematic review found strong evidence supporting benefits of several therapies over placebo, including metronidazole, azelaic acid, brimonidine, tetracycline, doxycycline 40 mg, ivermectin, and isotretinoin (Br J Dermatol. 2015;173[3]:651-2). A separate, 7-year retrospective study of 275 adults with rosacea published online in The Journal of Dermatology on Oct. 28, 2015, found that patients with the PPR subtype had a better overall prognosis, compared with their counterparts with the other subtypes. Overall, the median time to complete remission was 56 months. Complete remission was achieved in 46% of those with PPR subtype, compared with 19% of those with mixed subtype and 11% of those with ETR subtype.

Dr. Gallo disclosed that he has received research grants from the National Institutes of Health, Allergan, L’Oreal, Colgate-Palmolive, Regeneron, GSK, Galderma, and Bayer. He is a consultant for Allergan, Colgate-Palmolive, Sente, Matrisys, Dermata, Alnylam, Abbvie, Roche, and Promius.

[email protected]

NEWPORT BEACH, CALIF. – In the clinical opinion of Richard L. Gallo, MD, PhD, current nomenclature for the diagnosis of rosacea could use a makeover.

“Currently, we’re still operating with an almost 20-year-old set of diagnostic subtypes of rosacea,” Dr. Gallo said at the annual meeting of the Pacific Dermatologic Association. He plans to participate in consensus meeting of experts who will convene this fall in an effort to update and modify these diagnostic criteria.

 

Dr. Richard L. Gallo

According to current nomenclature, subtype 1 is erythematotelangiectatic rosacea characterized by facial redness; subtype 2 is papulopustular, marked by bumps and pimples; subtype 3 is phymatous, characterized by enlargement of the nose, and subtype 4 is ocular, marked by eye irritation. Dr. Gallo pointed out that it’s rare to see just one of these subtypes in rosacea patients, with the exception of the erythematotelangiectatic rosacea (ETR). “There is a large population with ETR alone,” he said.” Most patients with the papulopustular subtype have aspects of ETR. There is a mix of subtypes of rosacea and we clearly need to modify our diagnostic criteria.”

 

Secondary rosacea features may include burning or stinging, plaque, dry appearance and scale, edema, ocular manifestations, peripheral location, and phymatous changes. Work by several researchers in recent years has shed light on the pathophysiology of rosacea. “We’re learning that there are many aspects to this disease that both trigger it and result in progression of the disease,” said Dr. Gallo, professor and chair of the department of dermatology at the University of California, San Diego. “It seems to have biological triggers that exist both in the environment and initiate from internal sources. We’re understanding more about the nature of those, at least specific molecules externally from microbes and so forth. Internally we understand more about the unique inflammatory signals.”

For example, he and other researchers began to look at the innate immune system patients with rosacea and identified LL37, a multifunction peptide that plays a role in a number of skin diseases, as something that can promote inflammation (Nat Med. 2007;13[8]:975-80). “It also promotes the vascular changes [that occur with the disease],” Dr. Gallo said. “We’re now learning how a dysregulation of enzymes in the skin contributes to making too much of these types of peptides. Therefore, treatment approaches that might modify enzymatic activity become useful.” Researchers have also discovered that some of the innate recognition molecules like toll-like receptor 2 (TLR2) are overexpressed in rosacea patients. “Similarly, in terms of the vascular signals, a number of labs are identifying some of the newer vascular transmitters that seem to be uniquely elevated in rosacea, so there’s great reason to be optimistic that given the increased specificity and understanding of what uniquely makes this disease happen, we’ll be able to target it in a safe way.”

A number of published studies have supported these notions, including an analysis of 275 twin pairs (JAMA Dermatol. 2015;151[11]:1213-9). The researchers found that compared with fraternal twins, identical twins had a higher association of National Rosacea Society scores (P = .04), “supporting the concept that there are fundamental genetic factors that are influencing disease,” Dr. Gallo said. Environmental factors found to be associated with rosacea include lifetime UV exposure, smoking, obesity, and alcohol use.

In an assessment of the genetic basis of rosacea by genome-wide association study, researchers identified one confirmed single-nucleotide polymorphism that could be associated with rosacea (J Invest Dermatol. 2015;135[6]:1548-55). It was located in an intergenic region between HLA-DRA and BTNL2, “which is consistent with the overall concept that there is perhaps a genetic abnormality that is leading to increased amino modulation of difficulties,” Dr. Gallo said. For another recent study, researchers analyzed 14 randomized or case control trials involving rosacea patients (Int J Med Sci. 2015;12[5]:387-96). They concluded that vasculature, chronic inflammatory responses, environmental triggers, food and chemicals ingested, and microorganisms either alone or in combination are responsible for rosacea.

Dr. Gallo went on to highlight findings from several studies that link rosacea to an increased risk for certain comorbidities. One, a nationwide case-control study from Taiwan that comprised 35,553 rosacea patients, found that the disease was significantly associated with a risk of certain cardiovascular comorbidities (J Acad Dermatol. 2015;73:249-54). These included dyslipidemia (OR 1.41), coronary artery disease (OR 1.35), and hypertension (OR 1.17). A separate analysis, based 93,314 participants in the Nurse’s Health Study, found that rosacea was significantly associated with a risk of coronary artery disease (OR 2.2). The researchers also observed that comorbidities seemed to increase with duration of the disease (Clin Gastroenterol Hepatol. 2016;14[2]:220-5). Another smaller case-control study of 65 patients and 65 controls found an increased risk with rosacea for coronary artery disease, hyperlipidemia, hypertension, and gastroesophageal reflux disease (J Am Acad Dermatol. 2015;73[4]:604-8).

 

 

A recent analysis of 75,088 participants in the Nurses’ Health Study found that women with rosacea faced an increased risk of thyroid cancer (HR 1.59) and basal cell carcinoma (HR 1.50; Br J Cancer 2015;113[3]:520-3). Rosacea may also impact one’s risk for developing certain neurological conditions. One study found an increased risk for dementia (HR 1.42) and Alzheimer’s disease (HR 1.92; Ann Neurol. 2016;79:921-8), while another found an increased risk for Parkinson’s disease (an adjusted incident ratio of 1.71 in patients with rosacea, compared with the referent population; JAMA Neurol. 2016;73[5]:529-34).

As for therapy, a recent Cochrane systematic review found strong evidence supporting benefits of several therapies over placebo, including metronidazole, azelaic acid, brimonidine, tetracycline, doxycycline 40 mg, ivermectin, and isotretinoin (Br J Dermatol. 2015;173[3]:651-2). A separate, 7-year retrospective study of 275 adults with rosacea published online in The Journal of Dermatology on Oct. 28, 2015, found that patients with the PPR subtype had a better overall prognosis, compared with their counterparts with the other subtypes. Overall, the median time to complete remission was 56 months. Complete remission was achieved in 46% of those with PPR subtype, compared with 19% of those with mixed subtype and 11% of those with ETR subtype.

Dr. Gallo disclosed that he has received research grants from the National Institutes of Health, Allergan, L’Oreal, Colgate-Palmolive, Regeneron, GSK, Galderma, and Bayer. He is a consultant for Allergan, Colgate-Palmolive, Sente, Matrisys, Dermata, Alnylam, Abbvie, Roche, and Promius.

[email protected]

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EXPERT ANALYSIS AT PDA 2016

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Most sepsis cases begin outside of the hospital

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Sepsis is a medical emergency that begins outside of the hospital in 79% of cases. In addition, 72% of patients with sepsis had recently used healthcare services or had chronic diseases that required frequent medical care.

Those are key findings from a special report in Morbidity and Mortality Weekly Report published by the U.S. Centers for Disease Control and Prevention (Morb Mortal Wkly Rep. 2016 Aug 23. doi: 10.15585/mmwr.mm6533e1).

“The treatment of sepsis is a race against time,” CDC Director Tom Frieden, MD, said during a media teleconference about the report. “We can protect more people from sepsis by informing patients and their families, treating infections promptly, and acting fast when sepsis does occur.”

Each year, between 1 and 3 million people in the United States are diagnosed with sepsis, a syndrome marked by the body’s overwhelming and life-threatening response to an infection, Dr. Frieden said. Of these, 15%-30% will die from the condition, for which there is no blood test. “Health care providers are on the front lines of both sepsis prevention and early recognition,” he emphasized. “Prevention really is possible.” For example, he continued, if a patient with diabetes visits their regular doctor and is found to have increased blood sugar and a small wound on their foot, “this is a prime opportunity to think about infection and reduce the risk of sepsis. In addition to treating the infection, the clinician can inform the patient and family members about how to care for the wound, how to recognize the signs that the infection may be getting worse, and when to seek additional medical care. If the infection gets worse the patient could be at risk for sepsis. Taking the opportunity to both treat and inform patients could save their life, and helping patients know to ask, ‘Could this be sepsis?’ empowers patients and families and could save lives.”

In an effort to describe the characteristics of patients with sepsis, researchers from the CDC and from New York State conducted a retrospective review of medical records from 246 adults and 79 children with sepsis who were treated at four New York hospitals. They found that sepsis most often occurs in patients older than age 65 years and in infants younger than 1 year of age, and the median hospital length of stay is 10 days. Six key signs and symptoms of sepsis were shivering or feeling cold; pain or discomfort; clammy or sweaty skin; being confused or disoriented; shortness of breath, and having a rapid heartbeat. “People with chronic diseases such as diabetes or weakened immune systems from things like tobacco use are at higher risk of sepsis,” Dr. Frieden said. “But even healthy people can develop sepsis from an infection, especially if it’s not treated properly and promptly.”

The four types of infections most commonly associated with sepsis include those involving the lungs, urinary tract, skin, and intestines, while the most common germs that can cause sepsis are Staphylococcus aureus, Escherichia coli (E. coli), and some types of Streptococcus. Infection prevention strategies such as increasing vaccination rates for pneumococcal disease and for influenza are likely to reduce the incidence of sepsis, according to the report. “We could also improve infections by improving handwashing at health care facilities as well as in the community,” Dr. Frieden added. “We can [also] improve recognition of sepsis both in the community and in health care facilities and act fast if sepsis is suspected in a patient. We’ve been able to reduce the rates of some infections that cause sepsis in health care facilities by half, but preventing more infections and stopping the spread of antibiotic resistant infections will protect even more patients from sepsis.”

Mitchell Levy, MD, founding member of the Surviving Sepsis Campaign, said during the teleconference that clinicians have made “tremendous progress in sepsis,” despite current challenges. “First, we now understand the importance of early identification and treatment of sepsis,” he said. “Second, we have seen improved survival through routine screening and treatment that is integrated into the work flow of hospitals. And third, frontline health care providers really do make a difference. What’s clear is that we need to expand these successes to other parts of hospitals and to other care locations.”

Forthcoming free CDC webinars related to sepsis for health care providers include one on Sept. 13 at 3 p.m., ET, entitled “Advances in Sepsis: Protecting Patients Throughout the Lifespan.” Another webinar will be offered on Sept. 22 at 2 p.m., ET, entitled “Empowering Nurses for Early Sepsis Recognition.”

 

 

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Sepsis is a medical emergency that begins outside of the hospital in 79% of cases. In addition, 72% of patients with sepsis had recently used healthcare services or had chronic diseases that required frequent medical care.

Those are key findings from a special report in Morbidity and Mortality Weekly Report published by the U.S. Centers for Disease Control and Prevention (Morb Mortal Wkly Rep. 2016 Aug 23. doi: 10.15585/mmwr.mm6533e1).

“The treatment of sepsis is a race against time,” CDC Director Tom Frieden, MD, said during a media teleconference about the report. “We can protect more people from sepsis by informing patients and their families, treating infections promptly, and acting fast when sepsis does occur.”

Each year, between 1 and 3 million people in the United States are diagnosed with sepsis, a syndrome marked by the body’s overwhelming and life-threatening response to an infection, Dr. Frieden said. Of these, 15%-30% will die from the condition, for which there is no blood test. “Health care providers are on the front lines of both sepsis prevention and early recognition,” he emphasized. “Prevention really is possible.” For example, he continued, if a patient with diabetes visits their regular doctor and is found to have increased blood sugar and a small wound on their foot, “this is a prime opportunity to think about infection and reduce the risk of sepsis. In addition to treating the infection, the clinician can inform the patient and family members about how to care for the wound, how to recognize the signs that the infection may be getting worse, and when to seek additional medical care. If the infection gets worse the patient could be at risk for sepsis. Taking the opportunity to both treat and inform patients could save their life, and helping patients know to ask, ‘Could this be sepsis?’ empowers patients and families and could save lives.”

In an effort to describe the characteristics of patients with sepsis, researchers from the CDC and from New York State conducted a retrospective review of medical records from 246 adults and 79 children with sepsis who were treated at four New York hospitals. They found that sepsis most often occurs in patients older than age 65 years and in infants younger than 1 year of age, and the median hospital length of stay is 10 days. Six key signs and symptoms of sepsis were shivering or feeling cold; pain or discomfort; clammy or sweaty skin; being confused or disoriented; shortness of breath, and having a rapid heartbeat. “People with chronic diseases such as diabetes or weakened immune systems from things like tobacco use are at higher risk of sepsis,” Dr. Frieden said. “But even healthy people can develop sepsis from an infection, especially if it’s not treated properly and promptly.”

The four types of infections most commonly associated with sepsis include those involving the lungs, urinary tract, skin, and intestines, while the most common germs that can cause sepsis are Staphylococcus aureus, Escherichia coli (E. coli), and some types of Streptococcus. Infection prevention strategies such as increasing vaccination rates for pneumococcal disease and for influenza are likely to reduce the incidence of sepsis, according to the report. “We could also improve infections by improving handwashing at health care facilities as well as in the community,” Dr. Frieden added. “We can [also] improve recognition of sepsis both in the community and in health care facilities and act fast if sepsis is suspected in a patient. We’ve been able to reduce the rates of some infections that cause sepsis in health care facilities by half, but preventing more infections and stopping the spread of antibiotic resistant infections will protect even more patients from sepsis.”

Mitchell Levy, MD, founding member of the Surviving Sepsis Campaign, said during the teleconference that clinicians have made “tremendous progress in sepsis,” despite current challenges. “First, we now understand the importance of early identification and treatment of sepsis,” he said. “Second, we have seen improved survival through routine screening and treatment that is integrated into the work flow of hospitals. And third, frontline health care providers really do make a difference. What’s clear is that we need to expand these successes to other parts of hospitals and to other care locations.”

Forthcoming free CDC webinars related to sepsis for health care providers include one on Sept. 13 at 3 p.m., ET, entitled “Advances in Sepsis: Protecting Patients Throughout the Lifespan.” Another webinar will be offered on Sept. 22 at 2 p.m., ET, entitled “Empowering Nurses for Early Sepsis Recognition.”

 

 

[email protected]

Sepsis is a medical emergency that begins outside of the hospital in 79% of cases. In addition, 72% of patients with sepsis had recently used healthcare services or had chronic diseases that required frequent medical care.

Those are key findings from a special report in Morbidity and Mortality Weekly Report published by the U.S. Centers for Disease Control and Prevention (Morb Mortal Wkly Rep. 2016 Aug 23. doi: 10.15585/mmwr.mm6533e1).

“The treatment of sepsis is a race against time,” CDC Director Tom Frieden, MD, said during a media teleconference about the report. “We can protect more people from sepsis by informing patients and their families, treating infections promptly, and acting fast when sepsis does occur.”

Each year, between 1 and 3 million people in the United States are diagnosed with sepsis, a syndrome marked by the body’s overwhelming and life-threatening response to an infection, Dr. Frieden said. Of these, 15%-30% will die from the condition, for which there is no blood test. “Health care providers are on the front lines of both sepsis prevention and early recognition,” he emphasized. “Prevention really is possible.” For example, he continued, if a patient with diabetes visits their regular doctor and is found to have increased blood sugar and a small wound on their foot, “this is a prime opportunity to think about infection and reduce the risk of sepsis. In addition to treating the infection, the clinician can inform the patient and family members about how to care for the wound, how to recognize the signs that the infection may be getting worse, and when to seek additional medical care. If the infection gets worse the patient could be at risk for sepsis. Taking the opportunity to both treat and inform patients could save their life, and helping patients know to ask, ‘Could this be sepsis?’ empowers patients and families and could save lives.”

In an effort to describe the characteristics of patients with sepsis, researchers from the CDC and from New York State conducted a retrospective review of medical records from 246 adults and 79 children with sepsis who were treated at four New York hospitals. They found that sepsis most often occurs in patients older than age 65 years and in infants younger than 1 year of age, and the median hospital length of stay is 10 days. Six key signs and symptoms of sepsis were shivering or feeling cold; pain or discomfort; clammy or sweaty skin; being confused or disoriented; shortness of breath, and having a rapid heartbeat. “People with chronic diseases such as diabetes or weakened immune systems from things like tobacco use are at higher risk of sepsis,” Dr. Frieden said. “But even healthy people can develop sepsis from an infection, especially if it’s not treated properly and promptly.”

The four types of infections most commonly associated with sepsis include those involving the lungs, urinary tract, skin, and intestines, while the most common germs that can cause sepsis are Staphylococcus aureus, Escherichia coli (E. coli), and some types of Streptococcus. Infection prevention strategies such as increasing vaccination rates for pneumococcal disease and for influenza are likely to reduce the incidence of sepsis, according to the report. “We could also improve infections by improving handwashing at health care facilities as well as in the community,” Dr. Frieden added. “We can [also] improve recognition of sepsis both in the community and in health care facilities and act fast if sepsis is suspected in a patient. We’ve been able to reduce the rates of some infections that cause sepsis in health care facilities by half, but preventing more infections and stopping the spread of antibiotic resistant infections will protect even more patients from sepsis.”

Mitchell Levy, MD, founding member of the Surviving Sepsis Campaign, said during the teleconference that clinicians have made “tremendous progress in sepsis,” despite current challenges. “First, we now understand the importance of early identification and treatment of sepsis,” he said. “Second, we have seen improved survival through routine screening and treatment that is integrated into the work flow of hospitals. And third, frontline health care providers really do make a difference. What’s clear is that we need to expand these successes to other parts of hospitals and to other care locations.”

Forthcoming free CDC webinars related to sepsis for health care providers include one on Sept. 13 at 3 p.m., ET, entitled “Advances in Sepsis: Protecting Patients Throughout the Lifespan.” Another webinar will be offered on Sept. 22 at 2 p.m., ET, entitled “Empowering Nurses for Early Sepsis Recognition.”

 

 

[email protected]

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Key clinical point: Sepsis is a significant public health and clinical management challenge.

Major finding: Sepsis begins outside of the hospital in 79% of cases.

Data source: A retrospective review of medical records from 246 adults and 79 children with sepsis who were treated at four New York hospitals.

Disclosures: The researchers reported having no financial disclosures.

Epilepsy has wide-ranging psychosocial impact on youth

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Epilepsy has wide-ranging psychosocial impact on youth

The psychosocial impact of epilepsy on children and adolescents is profound, ranging from a sense of vulnerability and disempowerment to discrimination, results from a systematic review of medical literature suggest.

“Children and adolescents perceive that epilepsy forces them to relinquish their sense of privacy, bodily control, normality, freedom, and confidence to participate in school and social activities,” researchers led by Lauren Chong wrote in a study published online Aug. 10 in Pediatrics. “They are overwhelmed by the daily uncertainties attributed to the unpredictable timing and potential harm from seizures, side effects of ongoing treatment, and the impermanence of remission.”

©IvelinRadkov/Thinkstock

In an effort to describe the perspectives of children and adolescents with epilepsy, Ms. Chong of the Sydney School of Public Health at the University of Sydney, New South Wales, Australia, and her associates searched Medline and other key databases for qualitative primary studies on children’s experience of epilepsy from inception to August 2015 (Pediatrics. 2016;138[3]:e20160658. doi: 10.1542/peds.2016-0658). They used thematic synthesis to analyze their findings. The final analysis included 43 articles involving 951 children and adolescents aged 3-21 years from 21 different countries. Articles written in a language other than English were excluded.

The researchers identified six themes: loss of bodily control such as a sense of being overtaken and alertness to mortality; loss of privacy such as humiliating involuntary function and unwanted special attention; inescapable inferiority and discrimination such as vulnerability to prejudice and inability to achieve academically; therapeutic burden and futility such as financial burden and insurmountable side effects; navigating health care such as unexpected necessity of transition as well as fragmented and inconsistent care; and recontextualizing to regain normality such as distinguishing disease from identity and gaining perspective and maturity.

The researchers observed some differences in experiences and perspectives based on patient age and disease severity. For example, “feelings of loss and abnormality tended to be expressed more strongly by older adolescent patients,” they wrote. “As young adults, they were aware of the potentially serious ramifications of epilepsy on their future, including their independence, school performance, vocation, and relationships. Teenage patients were more frustrated by social limitations on partying, drinking, and sleepovers that differentiated them from their peers.” Patients with more severe disease, meanwhile, “contended with disempowerment and seemed less able to delineate epilepsy from their identity. They seemed more willing to trial therapies that may work and some, on being told they would not achieve remission, chose to disengage from the health care system, deeming further treatment or follow-up to be futile.”

Suggestions for clinical practice based on the analysis include providing access to support groups of other epilepsy sufferers or other children/adolescents with chronic disease; facilitating liaisons between clinicians, families, and school teachers, and delivering coordinated care with psychologists and psychiatrists to address psychosocial aspects of epilepsy.

“Treatment and management should address the psychosocial needs of patients regarding stigma, present lifestyle limitations, and future concerns,” the researchers wrote. “These suggestions may inform strategies for practice and research that may contribute toward the improved [quality of life], therapeutic satisfaction, and health outcomes of children and adolescents with epilepsy.”

Ms. Chong is supported by the University of Sydney Neuroscience Network Research Scholarship. Another coauthor, Allison Tong, PhD, is supported by the National Health and Medical Research Council Fellowship. The researchers reported having no financial disclosures.

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The psychosocial impact of epilepsy on children and adolescents is profound, ranging from a sense of vulnerability and disempowerment to discrimination, results from a systematic review of medical literature suggest.

“Children and adolescents perceive that epilepsy forces them to relinquish their sense of privacy, bodily control, normality, freedom, and confidence to participate in school and social activities,” researchers led by Lauren Chong wrote in a study published online Aug. 10 in Pediatrics. “They are overwhelmed by the daily uncertainties attributed to the unpredictable timing and potential harm from seizures, side effects of ongoing treatment, and the impermanence of remission.”

©IvelinRadkov/Thinkstock

In an effort to describe the perspectives of children and adolescents with epilepsy, Ms. Chong of the Sydney School of Public Health at the University of Sydney, New South Wales, Australia, and her associates searched Medline and other key databases for qualitative primary studies on children’s experience of epilepsy from inception to August 2015 (Pediatrics. 2016;138[3]:e20160658. doi: 10.1542/peds.2016-0658). They used thematic synthesis to analyze their findings. The final analysis included 43 articles involving 951 children and adolescents aged 3-21 years from 21 different countries. Articles written in a language other than English were excluded.

The researchers identified six themes: loss of bodily control such as a sense of being overtaken and alertness to mortality; loss of privacy such as humiliating involuntary function and unwanted special attention; inescapable inferiority and discrimination such as vulnerability to prejudice and inability to achieve academically; therapeutic burden and futility such as financial burden and insurmountable side effects; navigating health care such as unexpected necessity of transition as well as fragmented and inconsistent care; and recontextualizing to regain normality such as distinguishing disease from identity and gaining perspective and maturity.

The researchers observed some differences in experiences and perspectives based on patient age and disease severity. For example, “feelings of loss and abnormality tended to be expressed more strongly by older adolescent patients,” they wrote. “As young adults, they were aware of the potentially serious ramifications of epilepsy on their future, including their independence, school performance, vocation, and relationships. Teenage patients were more frustrated by social limitations on partying, drinking, and sleepovers that differentiated them from their peers.” Patients with more severe disease, meanwhile, “contended with disempowerment and seemed less able to delineate epilepsy from their identity. They seemed more willing to trial therapies that may work and some, on being told they would not achieve remission, chose to disengage from the health care system, deeming further treatment or follow-up to be futile.”

Suggestions for clinical practice based on the analysis include providing access to support groups of other epilepsy sufferers or other children/adolescents with chronic disease; facilitating liaisons between clinicians, families, and school teachers, and delivering coordinated care with psychologists and psychiatrists to address psychosocial aspects of epilepsy.

“Treatment and management should address the psychosocial needs of patients regarding stigma, present lifestyle limitations, and future concerns,” the researchers wrote. “These suggestions may inform strategies for practice and research that may contribute toward the improved [quality of life], therapeutic satisfaction, and health outcomes of children and adolescents with epilepsy.”

Ms. Chong is supported by the University of Sydney Neuroscience Network Research Scholarship. Another coauthor, Allison Tong, PhD, is supported by the National Health and Medical Research Council Fellowship. The researchers reported having no financial disclosures.

[email protected]

The psychosocial impact of epilepsy on children and adolescents is profound, ranging from a sense of vulnerability and disempowerment to discrimination, results from a systematic review of medical literature suggest.

“Children and adolescents perceive that epilepsy forces them to relinquish their sense of privacy, bodily control, normality, freedom, and confidence to participate in school and social activities,” researchers led by Lauren Chong wrote in a study published online Aug. 10 in Pediatrics. “They are overwhelmed by the daily uncertainties attributed to the unpredictable timing and potential harm from seizures, side effects of ongoing treatment, and the impermanence of remission.”

©IvelinRadkov/Thinkstock

In an effort to describe the perspectives of children and adolescents with epilepsy, Ms. Chong of the Sydney School of Public Health at the University of Sydney, New South Wales, Australia, and her associates searched Medline and other key databases for qualitative primary studies on children’s experience of epilepsy from inception to August 2015 (Pediatrics. 2016;138[3]:e20160658. doi: 10.1542/peds.2016-0658). They used thematic synthesis to analyze their findings. The final analysis included 43 articles involving 951 children and adolescents aged 3-21 years from 21 different countries. Articles written in a language other than English were excluded.

The researchers identified six themes: loss of bodily control such as a sense of being overtaken and alertness to mortality; loss of privacy such as humiliating involuntary function and unwanted special attention; inescapable inferiority and discrimination such as vulnerability to prejudice and inability to achieve academically; therapeutic burden and futility such as financial burden and insurmountable side effects; navigating health care such as unexpected necessity of transition as well as fragmented and inconsistent care; and recontextualizing to regain normality such as distinguishing disease from identity and gaining perspective and maturity.

The researchers observed some differences in experiences and perspectives based on patient age and disease severity. For example, “feelings of loss and abnormality tended to be expressed more strongly by older adolescent patients,” they wrote. “As young adults, they were aware of the potentially serious ramifications of epilepsy on their future, including their independence, school performance, vocation, and relationships. Teenage patients were more frustrated by social limitations on partying, drinking, and sleepovers that differentiated them from their peers.” Patients with more severe disease, meanwhile, “contended with disempowerment and seemed less able to delineate epilepsy from their identity. They seemed more willing to trial therapies that may work and some, on being told they would not achieve remission, chose to disengage from the health care system, deeming further treatment or follow-up to be futile.”

Suggestions for clinical practice based on the analysis include providing access to support groups of other epilepsy sufferers or other children/adolescents with chronic disease; facilitating liaisons between clinicians, families, and school teachers, and delivering coordinated care with psychologists and psychiatrists to address psychosocial aspects of epilepsy.

“Treatment and management should address the psychosocial needs of patients regarding stigma, present lifestyle limitations, and future concerns,” the researchers wrote. “These suggestions may inform strategies for practice and research that may contribute toward the improved [quality of life], therapeutic satisfaction, and health outcomes of children and adolescents with epilepsy.”

Ms. Chong is supported by the University of Sydney Neuroscience Network Research Scholarship. Another coauthor, Allison Tong, PhD, is supported by the National Health and Medical Research Council Fellowship. The researchers reported having no financial disclosures.

[email protected]

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Key clinical point: Addressing stigma, future independence, and fear of death may improve the overall well-being of children with epilepsy.

Major finding: Children with epilepsy experience vulnerability, disempowerment, and discrimination.

Data source: A meta-analysis of 43 articles involving 951 children and adolescents with epilepsy aged 3-21 years.

Disclosures: Ms. Chong is supported by the University of Sydney Neuroscience Network Research Scholarship. Another coauthor, Allison Tong, PhD, is supported by the National Health and Medical Research Council Fellowship. The researchers reported having no financial disclosures.