Muckle-Wells syndrome (MWS) was first described in 1962 and is part of a broad category of hereditary periodic fever syndromes that include the autoinflammatory syndromes and the cryopyrin-associated periodic syndromes (CAPSs). Unlike autoimmune diseases, autoinflammatory syndromes are not associated with antigen-specific T-cell responses or high titers of autoantibodies but are related to disorders of the innate immune system. Basal cell nevus syndrome (BCNS), or Gorlin syndrome, is a rare genodermatosis inherited in an autosomal-dominant fashion that is characterized by a broad range of anomalies. Most notable is the early and strong predisposition to develop several to hundreds of basal cell carcinomas (BCCs). Classic clinical features of MWS and a thorough history and physical examination can assist in the diagnosis of this rare entity.

Case Report

A 35-year-old woman with a history of BCNS, which had been diagnosed at 24 years of age based on the presence of more than 2 BCCs and a family history of BCNS in her mother, presented with intermittent pruritic urticaria on the chest and back, episodic fevers, associated joint pain and swelling that worsened several hours after exercise, headache, conjunctivitis, blurred vision, and severe debilitating fatigue that had been present since childhood. The symptoms had progressively worsened with age and symptom-free intervals became shorter. She was diagnosed by her rheumatologist with biopsy-proven MWS and a positive NLRP3 (NLR family pyrin domain containing 3) gene mutation at 29 years of age. She was treated unsuccessfully with prednisone and antihistamines and entered a trial with anakinra. She showed improvement for 2 weeks but developed severe swelling and erythema at the injection sites at week 3, along with large leathery patches on the legs and difficulty ambulating.

The patient subsequently underwent excision of her BCCs and reported each site became erythematous, edematous, warm, and painful 6 hours after excision, which lasted for hours to days (Figures 1–3). After the first excision on the right forearm, she was seen in the emergency department, started on intravenous antibiotics and prednisone, and kept overnight in the hospital. She was discharged the following day and the edema in the right forearm subsided over several days. Bacterial culture and laboratory evaluation for infection were negative after the first excision on the right forearm. Because of the symptoms she experienced following this excision, she was referred to the plastic surgery department for excision followed by postoperative monitoring in the hospital. The patient continued to undergo excisions for BCCs and developed more severe symptoms including erythema, edema, warmth, and tenderness at the surrounding sites. Once again, the excision sites were cultured and laboratory work to rule out infection was ordered with a negative result. After several excisions and subsequent clinical findings, the patients’ symptoms were deemed consistent with MWS and not a result of infectious etiology. A diagnosis of MWS and BCNS with exacerbation of MWS with surgical procedures was made.

The patient has continued therapy with rilonacept for MWS, which is managed by her rheumatologist. She has tolerated rilonacept without adverse effects and has experienced a reduction in symptoms that has enhanced her quality of life and allows for further treatment of her BCNS. Her dermatologist (J.W.L.) has been treating her BCCs with vismodegib, but treatment has been sporadic due to muscle cramping after 7 days of therapy. She reported subjective improvement to her dermatologist and has tried alternating 7 days on and 7 days off vismodegib. The muscle cramping still has limited her treatment with this regimen, and she is currently on a trial of 3 days on, 4 days off per week.

Comment

Classification and Clinical Presentation
The hereditary periodic fever syndromes include the autoinflammatory syndromes and the CAPSs. The autoinflammatory syndromes include familial Mediterranean fever, hyperimmunoglobulinemia D with periodic fever syndrome, and tumor necrosis factor receptor–associated periodic syndrome. The CAPSs are similar but distinct and include familial cold autoinflammatory syndrome, neonatal-onset multisystem inflammatory disease (also known as chronic infantile neurologic cutaneous and articular syndrome, or cutaneous articular syndrome) and MWS.^1,2

Cryopyrin-associated periodic syndromes are rare inherited diseases that result from mutations in the NLRP3 gene. There is a gain-of-function mutation on the NLRP3 gene located on the long arm of chromosome 1 at position 44, which codes for cryopyrin. An NLRP3 gene mutation causes cryopyrin to become hyperactive, leading to the formation of an inflammasome, which is a group of cryopyrin molecules. Inflammasomes, along with other proteins, activate caspase 1 to produce excess IL-1β, leading to persistent inflammatory symptoms.³ IL-1β is one of the key mediators of the body’s response to microbial invasion, inflammation, immunologic reactions, and tissue injury. It affects a large range of cells and organs. Although IL-1β production is critical for the control of pathogenic infections, excessive cytokine production is harmful to the host and can even be fatal.^3,4

Cryopyrin-associated periodic syndromes encompass a disease continuum. The 3 distinct entities share many overlapping features as well as unique and distinguishing characteristics. Familial cold autoinflammatory syndrome is the mildest phenotype and is inherited in an autosomal-dominant fashion. It is characterized by a chronic urticarial eruption that starts early in infancy or childhood. The distribution of the cutaneous eruption is widespread and favors the arms and legs over the face and trunk. A low-grade fever often is seen along with musculoskeletal concerns of arthralgia and pain. Other commonly reported symptoms include conjunctivitis, myalgia, fatigue, and headache. Neurologic symptoms can include headaches. Symptoms usually begin 1 to 2 hours after cold exposure and last less than 24 hours.^5-8

Neonatal-onset multisystem inflammatory disease is the most severe phenotype and occurs sporadically. Continuous symptoms and flares are characteristic and the length of the flare can vary from minutes to days. The cutaneous eruption favors the face, trunk, arms, and legs, and varies in intensity, beginning in infancy or childhood. Fever may be intermittent, mild, or absent. Rheumatologic manifestations include arthralgia and swelling, with approximately one-third of patients experiencing severe disabling arthropathy that causes gross joint deformity. Ocular findings include conjunctivitis, uveitis, papilledema, and even blindness. Neurologic sequelae include headaches, sensorineural hearing loss, and aseptic meningitis. Amyloidosis has been seen as a late complication.^5,8

Muckle-Wells syndrome is a rare hereditary inflammatory disorder. It has no ethnic predisposition and is mostly inherited in an autosomal-dominant fashion. Classically, the condition is characterized by recurrent urticaria beginning at birth with intermittent episodic fever and malaise. The eruption has a predilection for the face, trunk, arms, and legs, which is similar to neonatal-onset multisystem inflammatory disease. Associated myalgia and arthralgia are common as well as ocular findings of conjunctivitis and episcleritis. Neurologic manifestations include headache and progressive sensorineural hearing loss in 60% to 70% of patients.⁶ Abdominal pain may be seen along with rare serositis in MWS but is rare in the other CAPSs. Amyloidosis caused by chronic inflammation is the most serious complication of MWS and is seen in approximately one-third of patients, manifesting as proteinuria followed by renal impairment. Symptoms of MWS may occur daily but vary individually, are broad in intensity and duration, and can last 1 to 2 days before resolving spontaneously. The symptoms can result from metabolic stressors including cold, stress, and exercise, as well as microbial pathogens. Leukocytosis and increased acute-phase reactants are observed during episodes of inflammation.^4,6,8

Histopathology
Mild phenotypic variability exists between individuals, and many of the symptoms overlap in CAPSs. Although CAPSs display several distinguishing clinical characteristics, interestingly they share the same histopathological features regardless of the syndrome. The typical histopathological finding is a dermal neutrophilic infiltrate that tends to be perivascular and also may be perieccrine. Vasodilation and dermal edema also may be seen. These histopathological findings contrast with the typical lymphocytic and eosinophilic infiltrate seen in classic urticaria. Similar histopathologic findings have been seen in other neutrophilic urticarial dermatoses such as Schnitzler syndrome.^4,6

Differential
The differential diagnoses for CAPSs include Schnitzler syndrome, cold urticaria, systemic-onset juvenile idiopathic arthritis/adult-onset Still disease, and deficiency in IL-1ra. It is important to consider these differential diagnoses for management and treatment options.

Management
The discovery of the NLRP3 gene mutation as well as an understanding of IL-1 biology has led to targeted therapy for these syndromes. Cryopyrin-associated periodic syndromes are mediated by IL-1β with an in vivo rate 5 times higher than in healthy patients.⁴ The blockade of IL-1β results in complete resolution of symptoms.

In the last several years, anakinra, rilonacept, and canakinumab have shown efficacy in targeting IL-1β as receptor antagonists. Anakinra is a short-acting recombinant IL-1ra with a half-life of 4 to 6 hours. This short half-life requires daily injections and the most common adverse events included injection-site reaction and upper respiratory tract infection.^2,4 Rilonacept is a dimeric fusion protein that contains binding regions for the type 1 receptor and the IL-1 receptor accessory protein and is fused to the fragment, crystallizable (Fc) portion of human IgG1. Rilonacept is long acting with a circulating half-life of 8.6 days and offers patients ease of dosing with weekly subcutaneous injections. Rilonacept generally is well tolerated, with the most frequent adverse effects being injection-site reaction, upper respiratory tract infection, headache, arthralgia, and diarrhea.^2,7

The newest of the treatments for patients with CAPS is canakinumab. It is a fully human IL-1β monoclonal antibody that is specific for IL-1β and not other members of the IL-1 family. It has a mean half-life of 26 days and is dosed subcutaneously once every 8 weeks. The most common adverse effects include nasopharyngitis, rhinitis, nausea, diarrhea, and vertigo.⁴ In one study, most patients did not report injection-site reactions.⁷ Studies also are underway on VX-765, a caspace-1 targeted therapy that acts upstream in the IL-1β pathway. Treatment with anakinra, rilonacept, and canakinumab generally offers rapid and sustained remission in the majority of MWS patients and helps prevent the development of systemic amyloidosis and lessens the potential for end organ damage.^2,7

MWS and BCNS
Our patient had an unusual presentation of MWS complicated by BCNS, another rare autosomal-dominant inherited genodermatosis. In an extensive review of PubMed articles indexed for MEDLINE using the search terms Muckle-Wells syndrome and basal cell nevus syndrome, no association was identified between MWS and BCNS. Basal cell nevus syndrome is linked to PTCH1 (patched 1) gene mutation with an incidence of 1:150,000 in the United States and Europe and is characterized by a broad range of anomalies including skeletal abnormalities, ectopic calcification, odontogenic keratocysts, facial dysmorphism with macrocephaly, palmoplantar pits, and numerous tumors. Most notable is the early and strong predisposition to develop several to hundreds of BCCs.⁹

Conclusion

Muckle-Wells syndrome may go undiagnosed for many years or may be misdiagnosed as refractory urticaria, as in our patient. It is important to include periodic fever syndromes in the differential diagnosis of refractory urticaria with episodic fever to diagnose these cases of MWS earlier.

Muckle-Wells syndrome (MWS) was first described in 1962 and is part of a broad category of hereditary periodic fever syndromes that include the autoinflammatory syndromes and the cryopyrin-associated periodic syndromes (CAPSs). Unlike autoimmune diseases, autoinflammatory syndromes are not associated with antigen-specific T-cell responses or high titers of autoantibodies but are related to disorders of the innate immune system. Basal cell nevus syndrome (BCNS), or Gorlin syndrome, is a rare genodermatosis inherited in an autosomal-dominant fashion that is characterized by a broad range of anomalies. Most notable is the early and strong predisposition to develop several to hundreds of basal cell carcinomas (BCCs). Classic clinical features of MWS and a thorough history and physical examination can assist in the diagnosis of this rare entity.

Case Report

A 35-year-old woman with a history of BCNS, which had been diagnosed at 24 years of age based on the presence of more than 2 BCCs and a family history of BCNS in her mother, presented with intermittent pruritic urticaria on the chest and back, episodic fevers, associated joint pain and swelling that worsened several hours after exercise, headache, conjunctivitis, blurred vision, and severe debilitating fatigue that had been present since childhood. The symptoms had progressively worsened with age and symptom-free intervals became shorter. She was diagnosed by her rheumatologist with biopsy-proven MWS and a positive NLRP3 (NLR family pyrin domain containing 3) gene mutation at 29 years of age. She was treated unsuccessfully with prednisone and antihistamines and entered a trial with anakinra. She showed improvement for 2 weeks but developed severe swelling and erythema at the injection sites at week 3, along with large leathery patches on the legs and difficulty ambulating.

The patient subsequently underwent excision of her BCCs and reported each site became erythematous, edematous, warm, and painful 6 hours after excision, which lasted for hours to days (Figures 1–3). After the first excision on the right forearm, she was seen in the emergency department, started on intravenous antibiotics and prednisone, and kept overnight in the hospital. She was discharged the following day and the edema in the right forearm subsided over several days. Bacterial culture and laboratory evaluation for infection were negative after the first excision on the right forearm. Because of the symptoms she experienced following this excision, she was referred to the plastic surgery department for excision followed by postoperative monitoring in the hospital. The patient continued to undergo excisions for BCCs and developed more severe symptoms including erythema, edema, warmth, and tenderness at the surrounding sites. Once again, the excision sites were cultured and laboratory work to rule out infection was ordered with a negative result. After several excisions and subsequent clinical findings, the patients’ symptoms were deemed consistent with MWS and not a result of infectious etiology. A diagnosis of MWS and BCNS with exacerbation of MWS with surgical procedures was made.

The patient has continued therapy with rilonacept for MWS, which is managed by her rheumatologist. She has tolerated rilonacept without adverse effects and has experienced a reduction in symptoms that has enhanced her quality of life and allows for further treatment of her BCNS. Her dermatologist (J.W.L.) has been treating her BCCs with vismodegib, but treatment has been sporadic due to muscle cramping after 7 days of therapy. She reported subjective improvement to her dermatologist and has tried alternating 7 days on and 7 days off vismodegib. The muscle cramping still has limited her treatment with this regimen, and she is currently on a trial of 3 days on, 4 days off per week.

Comment

Classification and Clinical Presentation
The hereditary periodic fever syndromes include the autoinflammatory syndromes and the CAPSs. The autoinflammatory syndromes include familial Mediterranean fever, hyperimmunoglobulinemia D with periodic fever syndrome, and tumor necrosis factor receptor–associated periodic syndrome. The CAPSs are similar but distinct and include familial cold autoinflammatory syndrome, neonatal-onset multisystem inflammatory disease (also known as chronic infantile neurologic cutaneous and articular syndrome, or cutaneous articular syndrome) and MWS.^1,2

Cryopyrin-associated periodic syndromes are rare inherited diseases that result from mutations in the NLRP3 gene. There is a gain-of-function mutation on the NLRP3 gene located on the long arm of chromosome 1 at position 44, which codes for cryopyrin. An NLRP3 gene mutation causes cryopyrin to become hyperactive, leading to the formation of an inflammasome, which is a group of cryopyrin molecules. Inflammasomes, along with other proteins, activate caspase 1 to produce excess IL-1β, leading to persistent inflammatory symptoms.³ IL-1β is one of the key mediators of the body’s response to microbial invasion, inflammation, immunologic reactions, and tissue injury. It affects a large range of cells and organs. Although IL-1β production is critical for the control of pathogenic infections, excessive cytokine production is harmful to the host and can even be fatal.^3,4

Cryopyrin-associated periodic syndromes encompass a disease continuum. The 3 distinct entities share many overlapping features as well as unique and distinguishing characteristics. Familial cold autoinflammatory syndrome is the mildest phenotype and is inherited in an autosomal-dominant fashion. It is characterized by a chronic urticarial eruption that starts early in infancy or childhood. The distribution of the cutaneous eruption is widespread and favors the arms and legs over the face and trunk. A low-grade fever often is seen along with musculoskeletal concerns of arthralgia and pain. Other commonly reported symptoms include conjunctivitis, myalgia, fatigue, and headache. Neurologic symptoms can include headaches. Symptoms usually begin 1 to 2 hours after cold exposure and last less than 24 hours.^5-8

Neonatal-onset multisystem inflammatory disease is the most severe phenotype and occurs sporadically. Continuous symptoms and flares are characteristic and the length of the flare can vary from minutes to days. The cutaneous eruption favors the face, trunk, arms, and legs, and varies in intensity, beginning in infancy or childhood. Fever may be intermittent, mild, or absent. Rheumatologic manifestations include arthralgia and swelling, with approximately one-third of patients experiencing severe disabling arthropathy that causes gross joint deformity. Ocular findings include conjunctivitis, uveitis, papilledema, and even blindness. Neurologic sequelae include headaches, sensorineural hearing loss, and aseptic meningitis. Amyloidosis has been seen as a late complication.^5,8

Muckle-Wells syndrome is a rare hereditary inflammatory disorder. It has no ethnic predisposition and is mostly inherited in an autosomal-dominant fashion. Classically, the condition is characterized by recurrent urticaria beginning at birth with intermittent episodic fever and malaise. The eruption has a predilection for the face, trunk, arms, and legs, which is similar to neonatal-onset multisystem inflammatory disease. Associated myalgia and arthralgia are common as well as ocular findings of conjunctivitis and episcleritis. Neurologic manifestations include headache and progressive sensorineural hearing loss in 60% to 70% of patients.⁶ Abdominal pain may be seen along with rare serositis in MWS but is rare in the other CAPSs. Amyloidosis caused by chronic inflammation is the most serious complication of MWS and is seen in approximately one-third of patients, manifesting as proteinuria followed by renal impairment. Symptoms of MWS may occur daily but vary individually, are broad in intensity and duration, and can last 1 to 2 days before resolving spontaneously. The symptoms can result from metabolic stressors including cold, stress, and exercise, as well as microbial pathogens. Leukocytosis and increased acute-phase reactants are observed during episodes of inflammation.^4,6,8

Histopathology
Mild phenotypic variability exists between individuals, and many of the symptoms overlap in CAPSs. Although CAPSs display several distinguishing clinical characteristics, interestingly they share the same histopathological features regardless of the syndrome. The typical histopathological finding is a dermal neutrophilic infiltrate that tends to be perivascular and also may be perieccrine. Vasodilation and dermal edema also may be seen. These histopathological findings contrast with the typical lymphocytic and eosinophilic infiltrate seen in classic urticaria. Similar histopathologic findings have been seen in other neutrophilic urticarial dermatoses such as Schnitzler syndrome.^4,6

Differential
The differential diagnoses for CAPSs include Schnitzler syndrome, cold urticaria, systemic-onset juvenile idiopathic arthritis/adult-onset Still disease, and deficiency in IL-1ra. It is important to consider these differential diagnoses for management and treatment options.

Management
The discovery of the NLRP3 gene mutation as well as an understanding of IL-1 biology has led to targeted therapy for these syndromes. Cryopyrin-associated periodic syndromes are mediated by IL-1β with an in vivo rate 5 times higher than in healthy patients.⁴ The blockade of IL-1β results in complete resolution of symptoms.

In the last several years, anakinra, rilonacept, and canakinumab have shown efficacy in targeting IL-1β as receptor antagonists. Anakinra is a short-acting recombinant IL-1ra with a half-life of 4 to 6 hours. This short half-life requires daily injections and the most common adverse events included injection-site reaction and upper respiratory tract infection.^2,4 Rilonacept is a dimeric fusion protein that contains binding regions for the type 1 receptor and the IL-1 receptor accessory protein and is fused to the fragment, crystallizable (Fc) portion of human IgG1. Rilonacept is long acting with a circulating half-life of 8.6 days and offers patients ease of dosing with weekly subcutaneous injections. Rilonacept generally is well tolerated, with the most frequent adverse effects being injection-site reaction, upper respiratory tract infection, headache, arthralgia, and diarrhea.^2,7

The newest of the treatments for patients with CAPS is canakinumab. It is a fully human IL-1β monoclonal antibody that is specific for IL-1β and not other members of the IL-1 family. It has a mean half-life of 26 days and is dosed subcutaneously once every 8 weeks. The most common adverse effects include nasopharyngitis, rhinitis, nausea, diarrhea, and vertigo.⁴ In one study, most patients did not report injection-site reactions.⁷ Studies also are underway on VX-765, a caspace-1 targeted therapy that acts upstream in the IL-1β pathway. Treatment with anakinra, rilonacept, and canakinumab generally offers rapid and sustained remission in the majority of MWS patients and helps prevent the development of systemic amyloidosis and lessens the potential for end organ damage.^2,7

MWS and BCNS
Our patient had an unusual presentation of MWS complicated by BCNS, another rare autosomal-dominant inherited genodermatosis. In an extensive review of PubMed articles indexed for MEDLINE using the search terms Muckle-Wells syndrome and basal cell nevus syndrome, no association was identified between MWS and BCNS. Basal cell nevus syndrome is linked to PTCH1 (patched 1) gene mutation with an incidence of 1:150,000 in the United States and Europe and is characterized by a broad range of anomalies including skeletal abnormalities, ectopic calcification, odontogenic keratocysts, facial dysmorphism with macrocephaly, palmoplantar pits, and numerous tumors. Most notable is the early and strong predisposition to develop several to hundreds of BCCs.⁹

Conclusion

Muckle-Wells syndrome may go undiagnosed for many years or may be misdiagnosed as refractory urticaria, as in our patient. It is important to include periodic fever syndromes in the differential diagnosis of refractory urticaria with episodic fever to diagnose these cases of MWS earlier.

Muckle-Wells syndrome (MWS) was first described in 1962 and is part of a broad category of hereditary periodic fever syndromes that include the autoinflammatory syndromes and the cryopyrin-associated periodic syndromes (CAPSs). Unlike autoimmune diseases, autoinflammatory syndromes are not associated with antigen-specific T-cell responses or high titers of autoantibodies but are related to disorders of the innate immune system. Basal cell nevus syndrome (BCNS), or Gorlin syndrome, is a rare genodermatosis inherited in an autosomal-dominant fashion that is characterized by a broad range of anomalies. Most notable is the early and strong predisposition to develop several to hundreds of basal cell carcinomas (BCCs). Classic clinical features of MWS and a thorough history and physical examination can assist in the diagnosis of this rare entity.

Case Report

A 35-year-old woman with a history of BCNS, which had been diagnosed at 24 years of age based on the presence of more than 2 BCCs and a family history of BCNS in her mother, presented with intermittent pruritic urticaria on the chest and back, episodic fevers, associated joint pain and swelling that worsened several hours after exercise, headache, conjunctivitis, blurred vision, and severe debilitating fatigue that had been present since childhood. The symptoms had progressively worsened with age and symptom-free intervals became shorter. She was diagnosed by her rheumatologist with biopsy-proven MWS and a positive NLRP3 (NLR family pyrin domain containing 3) gene mutation at 29 years of age. She was treated unsuccessfully with prednisone and antihistamines and entered a trial with anakinra. She showed improvement for 2 weeks but developed severe swelling and erythema at the injection sites at week 3, along with large leathery patches on the legs and difficulty ambulating.

The patient subsequently underwent excision of her BCCs and reported each site became erythematous, edematous, warm, and painful 6 hours after excision, which lasted for hours to days (Figures 1–3). After the first excision on the right forearm, she was seen in the emergency department, started on intravenous antibiotics and prednisone, and kept overnight in the hospital. She was discharged the following day and the edema in the right forearm subsided over several days. Bacterial culture and laboratory evaluation for infection were negative after the first excision on the right forearm. Because of the symptoms she experienced following this excision, she was referred to the plastic surgery department for excision followed by postoperative monitoring in the hospital. The patient continued to undergo excisions for BCCs and developed more severe symptoms including erythema, edema, warmth, and tenderness at the surrounding sites. Once again, the excision sites were cultured and laboratory work to rule out infection was ordered with a negative result. After several excisions and subsequent clinical findings, the patients’ symptoms were deemed consistent with MWS and not a result of infectious etiology. A diagnosis of MWS and BCNS with exacerbation of MWS with surgical procedures was made.

The patient has continued therapy with rilonacept for MWS, which is managed by her rheumatologist. She has tolerated rilonacept without adverse effects and has experienced a reduction in symptoms that has enhanced her quality of life and allows for further treatment of her BCNS. Her dermatologist (J.W.L.) has been treating her BCCs with vismodegib, but treatment has been sporadic due to muscle cramping after 7 days of therapy. She reported subjective improvement to her dermatologist and has tried alternating 7 days on and 7 days off vismodegib. The muscle cramping still has limited her treatment with this regimen, and she is currently on a trial of 3 days on, 4 days off per week.

Comment

Classification and Clinical Presentation
The hereditary periodic fever syndromes include the autoinflammatory syndromes and the CAPSs. The autoinflammatory syndromes include familial Mediterranean fever, hyperimmunoglobulinemia D with periodic fever syndrome, and tumor necrosis factor receptor–associated periodic syndrome. The CAPSs are similar but distinct and include familial cold autoinflammatory syndrome, neonatal-onset multisystem inflammatory disease (also known as chronic infantile neurologic cutaneous and articular syndrome, or cutaneous articular syndrome) and MWS.^1,2

Cryopyrin-associated periodic syndromes are rare inherited diseases that result from mutations in the NLRP3 gene. There is a gain-of-function mutation on the NLRP3 gene located on the long arm of chromosome 1 at position 44, which codes for cryopyrin. An NLRP3 gene mutation causes cryopyrin to become hyperactive, leading to the formation of an inflammasome, which is a group of cryopyrin molecules. Inflammasomes, along with other proteins, activate caspase 1 to produce excess IL-1β, leading to persistent inflammatory symptoms.³ IL-1β is one of the key mediators of the body’s response to microbial invasion, inflammation, immunologic reactions, and tissue injury. It affects a large range of cells and organs. Although IL-1β production is critical for the control of pathogenic infections, excessive cytokine production is harmful to the host and can even be fatal.^3,4

Cryopyrin-associated periodic syndromes encompass a disease continuum. The 3 distinct entities share many overlapping features as well as unique and distinguishing characteristics. Familial cold autoinflammatory syndrome is the mildest phenotype and is inherited in an autosomal-dominant fashion. It is characterized by a chronic urticarial eruption that starts early in infancy or childhood. The distribution of the cutaneous eruption is widespread and favors the arms and legs over the face and trunk. A low-grade fever often is seen along with musculoskeletal concerns of arthralgia and pain. Other commonly reported symptoms include conjunctivitis, myalgia, fatigue, and headache. Neurologic symptoms can include headaches. Symptoms usually begin 1 to 2 hours after cold exposure and last less than 24 hours.^5-8

Neonatal-onset multisystem inflammatory disease is the most severe phenotype and occurs sporadically. Continuous symptoms and flares are characteristic and the length of the flare can vary from minutes to days. The cutaneous eruption favors the face, trunk, arms, and legs, and varies in intensity, beginning in infancy or childhood. Fever may be intermittent, mild, or absent. Rheumatologic manifestations include arthralgia and swelling, with approximately one-third of patients experiencing severe disabling arthropathy that causes gross joint deformity. Ocular findings include conjunctivitis, uveitis, papilledema, and even blindness. Neurologic sequelae include headaches, sensorineural hearing loss, and aseptic meningitis. Amyloidosis has been seen as a late complication.^5,8

Muckle-Wells syndrome is a rare hereditary inflammatory disorder. It has no ethnic predisposition and is mostly inherited in an autosomal-dominant fashion. Classically, the condition is characterized by recurrent urticaria beginning at birth with intermittent episodic fever and malaise. The eruption has a predilection for the face, trunk, arms, and legs, which is similar to neonatal-onset multisystem inflammatory disease. Associated myalgia and arthralgia are common as well as ocular findings of conjunctivitis and episcleritis. Neurologic manifestations include headache and progressive sensorineural hearing loss in 60% to 70% of patients.⁶ Abdominal pain may be seen along with rare serositis in MWS but is rare in the other CAPSs. Amyloidosis caused by chronic inflammation is the most serious complication of MWS and is seen in approximately one-third of patients, manifesting as proteinuria followed by renal impairment. Symptoms of MWS may occur daily but vary individually, are broad in intensity and duration, and can last 1 to 2 days before resolving spontaneously. The symptoms can result from metabolic stressors including cold, stress, and exercise, as well as microbial pathogens. Leukocytosis and increased acute-phase reactants are observed during episodes of inflammation.^4,6,8

Histopathology
Mild phenotypic variability exists between individuals, and many of the symptoms overlap in CAPSs. Although CAPSs display several distinguishing clinical characteristics, interestingly they share the same histopathological features regardless of the syndrome. The typical histopathological finding is a dermal neutrophilic infiltrate that tends to be perivascular and also may be perieccrine. Vasodilation and dermal edema also may be seen. These histopathological findings contrast with the typical lymphocytic and eosinophilic infiltrate seen in classic urticaria. Similar histopathologic findings have been seen in other neutrophilic urticarial dermatoses such as Schnitzler syndrome.^4,6

Differential
The differential diagnoses for CAPSs include Schnitzler syndrome, cold urticaria, systemic-onset juvenile idiopathic arthritis/adult-onset Still disease, and deficiency in IL-1ra. It is important to consider these differential diagnoses for management and treatment options.

Management
The discovery of the NLRP3 gene mutation as well as an understanding of IL-1 biology has led to targeted therapy for these syndromes. Cryopyrin-associated periodic syndromes are mediated by IL-1β with an in vivo rate 5 times higher than in healthy patients.⁴ The blockade of IL-1β results in complete resolution of symptoms.

In the last several years, anakinra, rilonacept, and canakinumab have shown efficacy in targeting IL-1β as receptor antagonists. Anakinra is a short-acting recombinant IL-1ra with a half-life of 4 to 6 hours. This short half-life requires daily injections and the most common adverse events included injection-site reaction and upper respiratory tract infection.^2,4 Rilonacept is a dimeric fusion protein that contains binding regions for the type 1 receptor and the IL-1 receptor accessory protein and is fused to the fragment, crystallizable (Fc) portion of human IgG1. Rilonacept is long acting with a circulating half-life of 8.6 days and offers patients ease of dosing with weekly subcutaneous injections. Rilonacept generally is well tolerated, with the most frequent adverse effects being injection-site reaction, upper respiratory tract infection, headache, arthralgia, and diarrhea.^2,7

The newest of the treatments for patients with CAPS is canakinumab. It is a fully human IL-1β monoclonal antibody that is specific for IL-1β and not other members of the IL-1 family. It has a mean half-life of 26 days and is dosed subcutaneously once every 8 weeks. The most common adverse effects include nasopharyngitis, rhinitis, nausea, diarrhea, and vertigo.⁴ In one study, most patients did not report injection-site reactions.⁷ Studies also are underway on VX-765, a caspace-1 targeted therapy that acts upstream in the IL-1β pathway. Treatment with anakinra, rilonacept, and canakinumab generally offers rapid and sustained remission in the majority of MWS patients and helps prevent the development of systemic amyloidosis and lessens the potential for end organ damage.^2,7

MWS and BCNS
Our patient had an unusual presentation of MWS complicated by BCNS, another rare autosomal-dominant inherited genodermatosis. In an extensive review of PubMed articles indexed for MEDLINE using the search terms Muckle-Wells syndrome and basal cell nevus syndrome, no association was identified between MWS and BCNS. Basal cell nevus syndrome is linked to PTCH1 (patched 1) gene mutation with an incidence of 1:150,000 in the United States and Europe and is characterized by a broad range of anomalies including skeletal abnormalities, ectopic calcification, odontogenic keratocysts, facial dysmorphism with macrocephaly, palmoplantar pits, and numerous tumors. Most notable is the early and strong predisposition to develop several to hundreds of BCCs.⁹

Conclusion

Muckle-Wells syndrome may go undiagnosed for many years or may be misdiagnosed as refractory urticaria, as in our patient. It is important to include periodic fever syndromes in the differential diagnosis of refractory urticaria with episodic fever to diagnose these cases of MWS earlier.

Dermatologic surgeons are susceptible to work-related ailments given the nature of their working posture, the most common of which are pain and stiffness in the neck, shoulders, and lower back, as well as headaches.^1,2 Awkward posture and positioning, for the sake of getting a better view of the task at hand, puts the surgeon in ergonomically disagreeable positions. Because the prime working years for a dermatologic surgeon tend to coincide with the age of presbyopia onset, magnification may help reduce and thwart musculoskeletal problems and eye strain. Indeed, a multitude of surgical specialties and dentists use intraoperative magnification.³ Knowledge and use of available magnification options can be a key addition to the dermatologic surgeon’s armamentarium. We discuss the need for magnification and review magnification devices that are readily available to the dermatologic surgeon. Table 1 presents a summary of all magnification options discussed.

Need for Magnification

Presbyopia is a condition of aging in which one loses the ability to accommodate and focus at near distances. The estimated prevalence of presbyopia in North America is 83%, typically with onset by 45 years of age.⁴ Individuals with presbyopia often hold objects farther away from their eyes to bring them into focus, causing eye strain, headaches, and musculoskeletal injury.

Use of intraoperative magnification allows for enhanced visualization of fine anatomic details and precise suture placement for the surgeon with or without presbyopia. Higher magnification produces a larger image; however, it also reduces field of view and depth of field (ie, the amount of depth that stays in focus without repositioning). The resolution and quality of the image are dependent on the optical properties of the lens system. The ideal optic system is surgeon dependent and involves a combination of magnification level that will not result in dramatic loss of view and depth of field, while maintaining crispness and quality of image.

Intraoperative magnification yields ergonomic benefits by promoting a safer neck flexion angle by increasing the working distance to a more ideal position (Figure). In doing so, it improves posture and minimizes eye and musculoskeletal strain secondary to awkward positioning and presbyopia.^1,5 Stationary working position and neck flexion and rotation with precise and repetitive tasks are risk factors for strain and injuries that dermatologic surgeons often encounter.¹ Magnification devices are tools that the dermatologic surgeon can utilize for a more ergonomically sound practice. Indeed, magnification has been shown to improve posture in the dental literature, a specialty with similar occupational risk factors to dermatologic surgery.^6-8 Ergonomic practice reduces occupational injuries and improves work quality and productivity, thereby having a favorable effect on both the patient and the physician.

Improved Outcomes With Magnification

There are many examples of improved surgical quality and outcomes with magnification in other specialties. Hart and Hall⁵ illustrated the advantage of magnification in laceration repairs in the emergency department. In one study, increased magnification resulted in a substantial decrease in positive surgical margin rates in open radical retropubic prostatectomy.⁹ Schoeffl et al¹⁰ demonstrated that the microsurgical success of fine surgical procedures was directly related to optical magnification strength when comparing the unaided eye, surgical loupes, and the operating microscope. The dental literature also has numerous examples of magnification producing improved quality dentistry.^11-13 Although magnification is not a novel concept to dermatologic surgery, little has been written about its use in the dermatologic surgery literature.

Magnification Options

One-Piece Bifocal Magnifying Safety Glasses
Bifocal magnifying safety glasses are polycarbonate safety glasses made with lenses in which the lower half is a magnifying lens. They are available in +1.5, +2.0, +2.5, and +3.0 diopter strengths. The total magnification power is calculated as follows: (diopter/4) + 1. The glasses are lightweight, easy to wear, inexpensive, and protect the eyes; however, they provide minimal magnification and do not compensate for differences in vision between both eyes.

Magnification Visor
The magnification visor is a headband visor with magnification lenses. It comes in various levels of magnification ranging from ×1.5 to ×3.5. It can be worn over prescription or safety glasses, may be pivoted out of the way when not in use, and is inexpensive. Conversely, it may be bulky to wear, cannot be customized, and does not offer the best resolution.

Magnification Clips
Magnification clips are hard-coated magnifying lens plates that fasten to eyeglass frames and range in level of magnification from ×1.5 to ×3.5. They can be pivoted out of the viewing angle, are lightweight, and are inexpensive; however, positioning may be difficult for ideal working distance and viewing angle.

Magnifier With Frame/Headband
The magnifier with frame is similar to magnification clips, but the magnification lens plate comes with a frame. It can be used with or without glasses and comes in magnification levels of ×1.5 to ×3.5. It is light, inexpensive, and may be pivoted out of sight, but similar to magnification clips, positioning for the right viewing angle and working distance may be difficult.

The magnifier with headband is essentially the same as the magnifier with frame. The only difference is the magnification plate is attached to a headband as opposed to a frame. It has similar benefits and limitations as the magnifier with frame.

Magnification Stand
The magnification stand comes as a large magnification lens with a flexible arm attached to a stand. It is a basic magnification tool and does not need to be worn; however, the stand is not easily portable and may be cumbersome to use.

Surgical Loupes
Surgical loupes are a robust magnification choice and the mainstay in magnification for the dermatologic surgeon. Loupes have proven to have comparable results in some procedures to the powerful operating surgical microscope.^14-17 Factors to consider with loupes include brand, design, lens, magnification, resolution, optimal working distance, field depth, and declination angle.¹⁸

The 2 surgical loupe designs—flip-up loupes and through-the-lens loupes—differ in the mounting of the optic lenses on safety glasses. Flip-up loupes have the optics mounted to the bridge of the frame, whereas through-the-lens loupes are fixed in the lenses.

There are 3 different optical systems for surgical loupe magnification: simple, compound, and prismatic. Simple lenses consist of one pair of positive meniscus lenses similar to reading glasses. Compound lenses are made of 2 magnification lenses. Prismatic lenses magnify using a prism that folds and lengthens the light path.^19,20

Loupes range in magnification level from ×2.5 to ×4.5. Compared to other magnification modalities, they can be customized and offer better resolution with quality magnification. Additionally, loupes can be fitted with a light source; however, they are expensive and surgeons need time to get used to the increased magnification as well as wearing the loupes.

There are advantages and disadvantages to the different loupe designs (Table 2). Flip-up loupes are more versatile, allowing for use on various safety glasses. They can be flipped out of view, and the declination angle may be altered; however, flip-up loupes have a narrower field of view and are heavier and bulkier than through-the-lens loupes. Through-the-lens loupes are lighter and have a larger field of view, as the optics are closer to the eye. They are customized to the declination angle and working distance of the surgeon. Conversely, through-the-lens loupes are more expensive and cannot be adjusted or moved from the line of vision.

Operating Surgical Microscope
The operating surgical microscope is not practical in the dermatologic surgeon’s practice. It is expensive and provides unnecessarily powerful magnification for dermatologic surgery. This tool usually is used in the operating room for suturing nerves and vessels with sutures sized 8-0 and smaller. Most skin procedures require size 6-0 and larger sutures.

Dermoscope
Dermoscopy, also known as epiluminescence microscopy, is a technique utilizing a handheld device made up of polarized light and a ×10 magnifying lens to evaluate skin lesions. In skilled hands, dermoscopy allows for the examination of characteristic patterns and morphologic features of skin lesions to enhance the clinician’s diagnostic accuracy.²¹ It may aid the dermatologic surgeon in identifying the surgical margins of difficult-to-define skin cancers. It is small and mobile; however, it has minimal benefit to the dermatologic surgeon during surgery because it is handheld and has a small field of view.

Conclusion

Good ergonomic practices facilitate a healthier and prolonged career for the dermatologic surgeon. When used properly, magnification devices can be a beneficial adjunct to the dermatologic surgeon by promoting better posture, preventing eyestrain, and providing enhanced visualization of the operating field and instruments. Use of magnification devices has been demonstrated to improve patient outcomes in other specialties. There are opportunities for further research specific to magnification improving dermatologic surgery outcomes given the high level of precision and accuracy needed for Mohs micrographic surgery, wound reconstruction, nail surgery, and hair transplantation.

Dermatologic surgeons are susceptible to work-related ailments given the nature of their working posture, the most common of which are pain and stiffness in the neck, shoulders, and lower back, as well as headaches.^1,2 Awkward posture and positioning, for the sake of getting a better view of the task at hand, puts the surgeon in ergonomically disagreeable positions. Because the prime working years for a dermatologic surgeon tend to coincide with the age of presbyopia onset, magnification may help reduce and thwart musculoskeletal problems and eye strain. Indeed, a multitude of surgical specialties and dentists use intraoperative magnification.³ Knowledge and use of available magnification options can be a key addition to the dermatologic surgeon’s armamentarium. We discuss the need for magnification and review magnification devices that are readily available to the dermatologic surgeon. Table 1 presents a summary of all magnification options discussed.

Need for Magnification

Presbyopia is a condition of aging in which one loses the ability to accommodate and focus at near distances. The estimated prevalence of presbyopia in North America is 83%, typically with onset by 45 years of age.⁴ Individuals with presbyopia often hold objects farther away from their eyes to bring them into focus, causing eye strain, headaches, and musculoskeletal injury.

Use of intraoperative magnification allows for enhanced visualization of fine anatomic details and precise suture placement for the surgeon with or without presbyopia. Higher magnification produces a larger image; however, it also reduces field of view and depth of field (ie, the amount of depth that stays in focus without repositioning). The resolution and quality of the image are dependent on the optical properties of the lens system. The ideal optic system is surgeon dependent and involves a combination of magnification level that will not result in dramatic loss of view and depth of field, while maintaining crispness and quality of image.

Intraoperative magnification yields ergonomic benefits by promoting a safer neck flexion angle by increasing the working distance to a more ideal position (Figure). In doing so, it improves posture and minimizes eye and musculoskeletal strain secondary to awkward positioning and presbyopia.^1,5 Stationary working position and neck flexion and rotation with precise and repetitive tasks are risk factors for strain and injuries that dermatologic surgeons often encounter.¹ Magnification devices are tools that the dermatologic surgeon can utilize for a more ergonomically sound practice. Indeed, magnification has been shown to improve posture in the dental literature, a specialty with similar occupational risk factors to dermatologic surgery.^6-8 Ergonomic practice reduces occupational injuries and improves work quality and productivity, thereby having a favorable effect on both the patient and the physician.

Improved Outcomes With Magnification

There are many examples of improved surgical quality and outcomes with magnification in other specialties. Hart and Hall⁵ illustrated the advantage of magnification in laceration repairs in the emergency department. In one study, increased magnification resulted in a substantial decrease in positive surgical margin rates in open radical retropubic prostatectomy.⁹ Schoeffl et al¹⁰ demonstrated that the microsurgical success of fine surgical procedures was directly related to optical magnification strength when comparing the unaided eye, surgical loupes, and the operating microscope. The dental literature also has numerous examples of magnification producing improved quality dentistry.^11-13 Although magnification is not a novel concept to dermatologic surgery, little has been written about its use in the dermatologic surgery literature.

Magnification Options

One-Piece Bifocal Magnifying Safety Glasses
Bifocal magnifying safety glasses are polycarbonate safety glasses made with lenses in which the lower half is a magnifying lens. They are available in +1.5, +2.0, +2.5, and +3.0 diopter strengths. The total magnification power is calculated as follows: (diopter/4) + 1. The glasses are lightweight, easy to wear, inexpensive, and protect the eyes; however, they provide minimal magnification and do not compensate for differences in vision between both eyes.

Magnification Visor
The magnification visor is a headband visor with magnification lenses. It comes in various levels of magnification ranging from ×1.5 to ×3.5. It can be worn over prescription or safety glasses, may be pivoted out of the way when not in use, and is inexpensive. Conversely, it may be bulky to wear, cannot be customized, and does not offer the best resolution.

Magnification Clips
Magnification clips are hard-coated magnifying lens plates that fasten to eyeglass frames and range in level of magnification from ×1.5 to ×3.5. They can be pivoted out of the viewing angle, are lightweight, and are inexpensive; however, positioning may be difficult for ideal working distance and viewing angle.

Magnifier With Frame/Headband
The magnifier with frame is similar to magnification clips, but the magnification lens plate comes with a frame. It can be used with or without glasses and comes in magnification levels of ×1.5 to ×3.5. It is light, inexpensive, and may be pivoted out of sight, but similar to magnification clips, positioning for the right viewing angle and working distance may be difficult.

The magnifier with headband is essentially the same as the magnifier with frame. The only difference is the magnification plate is attached to a headband as opposed to a frame. It has similar benefits and limitations as the magnifier with frame.

Magnification Stand
The magnification stand comes as a large magnification lens with a flexible arm attached to a stand. It is a basic magnification tool and does not need to be worn; however, the stand is not easily portable and may be cumbersome to use.

Surgical Loupes
Surgical loupes are a robust magnification choice and the mainstay in magnification for the dermatologic surgeon. Loupes have proven to have comparable results in some procedures to the powerful operating surgical microscope.^14-17 Factors to consider with loupes include brand, design, lens, magnification, resolution, optimal working distance, field depth, and declination angle.¹⁸

The 2 surgical loupe designs—flip-up loupes and through-the-lens loupes—differ in the mounting of the optic lenses on safety glasses. Flip-up loupes have the optics mounted to the bridge of the frame, whereas through-the-lens loupes are fixed in the lenses.

There are 3 different optical systems for surgical loupe magnification: simple, compound, and prismatic. Simple lenses consist of one pair of positive meniscus lenses similar to reading glasses. Compound lenses are made of 2 magnification lenses. Prismatic lenses magnify using a prism that folds and lengthens the light path.^19,20

Loupes range in magnification level from ×2.5 to ×4.5. Compared to other magnification modalities, they can be customized and offer better resolution with quality magnification. Additionally, loupes can be fitted with a light source; however, they are expensive and surgeons need time to get used to the increased magnification as well as wearing the loupes.

There are advantages and disadvantages to the different loupe designs (Table 2). Flip-up loupes are more versatile, allowing for use on various safety glasses. They can be flipped out of view, and the declination angle may be altered; however, flip-up loupes have a narrower field of view and are heavier and bulkier than through-the-lens loupes. Through-the-lens loupes are lighter and have a larger field of view, as the optics are closer to the eye. They are customized to the declination angle and working distance of the surgeon. Conversely, through-the-lens loupes are more expensive and cannot be adjusted or moved from the line of vision.

Operating Surgical Microscope
The operating surgical microscope is not practical in the dermatologic surgeon’s practice. It is expensive and provides unnecessarily powerful magnification for dermatologic surgery. This tool usually is used in the operating room for suturing nerves and vessels with sutures sized 8-0 and smaller. Most skin procedures require size 6-0 and larger sutures.

Dermoscope
Dermoscopy, also known as epiluminescence microscopy, is a technique utilizing a handheld device made up of polarized light and a ×10 magnifying lens to evaluate skin lesions. In skilled hands, dermoscopy allows for the examination of characteristic patterns and morphologic features of skin lesions to enhance the clinician’s diagnostic accuracy.²¹ It may aid the dermatologic surgeon in identifying the surgical margins of difficult-to-define skin cancers. It is small and mobile; however, it has minimal benefit to the dermatologic surgeon during surgery because it is handheld and has a small field of view.

Conclusion

Good ergonomic practices facilitate a healthier and prolonged career for the dermatologic surgeon. When used properly, magnification devices can be a beneficial adjunct to the dermatologic surgeon by promoting better posture, preventing eyestrain, and providing enhanced visualization of the operating field and instruments. Use of magnification devices has been demonstrated to improve patient outcomes in other specialties. There are opportunities for further research specific to magnification improving dermatologic surgery outcomes given the high level of precision and accuracy needed for Mohs micrographic surgery, wound reconstruction, nail surgery, and hair transplantation.

Dermatologic surgeons are susceptible to work-related ailments given the nature of their working posture, the most common of which are pain and stiffness in the neck, shoulders, and lower back, as well as headaches.^1,2 Awkward posture and positioning, for the sake of getting a better view of the task at hand, puts the surgeon in ergonomically disagreeable positions. Because the prime working years for a dermatologic surgeon tend to coincide with the age of presbyopia onset, magnification may help reduce and thwart musculoskeletal problems and eye strain. Indeed, a multitude of surgical specialties and dentists use intraoperative magnification.³ Knowledge and use of available magnification options can be a key addition to the dermatologic surgeon’s armamentarium. We discuss the need for magnification and review magnification devices that are readily available to the dermatologic surgeon. Table 1 presents a summary of all magnification options discussed.

Need for Magnification

Presbyopia is a condition of aging in which one loses the ability to accommodate and focus at near distances. The estimated prevalence of presbyopia in North America is 83%, typically with onset by 45 years of age.⁴ Individuals with presbyopia often hold objects farther away from their eyes to bring them into focus, causing eye strain, headaches, and musculoskeletal injury.

Use of intraoperative magnification allows for enhanced visualization of fine anatomic details and precise suture placement for the surgeon with or without presbyopia. Higher magnification produces a larger image; however, it also reduces field of view and depth of field (ie, the amount of depth that stays in focus without repositioning). The resolution and quality of the image are dependent on the optical properties of the lens system. The ideal optic system is surgeon dependent and involves a combination of magnification level that will not result in dramatic loss of view and depth of field, while maintaining crispness and quality of image.

Intraoperative magnification yields ergonomic benefits by promoting a safer neck flexion angle by increasing the working distance to a more ideal position (Figure). In doing so, it improves posture and minimizes eye and musculoskeletal strain secondary to awkward positioning and presbyopia.^1,5 Stationary working position and neck flexion and rotation with precise and repetitive tasks are risk factors for strain and injuries that dermatologic surgeons often encounter.¹ Magnification devices are tools that the dermatologic surgeon can utilize for a more ergonomically sound practice. Indeed, magnification has been shown to improve posture in the dental literature, a specialty with similar occupational risk factors to dermatologic surgery.^6-8 Ergonomic practice reduces occupational injuries and improves work quality and productivity, thereby having a favorable effect on both the patient and the physician.

Improved Outcomes With Magnification

There are many examples of improved surgical quality and outcomes with magnification in other specialties. Hart and Hall⁵ illustrated the advantage of magnification in laceration repairs in the emergency department. In one study, increased magnification resulted in a substantial decrease in positive surgical margin rates in open radical retropubic prostatectomy.⁹ Schoeffl et al¹⁰ demonstrated that the microsurgical success of fine surgical procedures was directly related to optical magnification strength when comparing the unaided eye, surgical loupes, and the operating microscope. The dental literature also has numerous examples of magnification producing improved quality dentistry.^11-13 Although magnification is not a novel concept to dermatologic surgery, little has been written about its use in the dermatologic surgery literature.

Magnification Options

One-Piece Bifocal Magnifying Safety Glasses
Bifocal magnifying safety glasses are polycarbonate safety glasses made with lenses in which the lower half is a magnifying lens. They are available in +1.5, +2.0, +2.5, and +3.0 diopter strengths. The total magnification power is calculated as follows: (diopter/4) + 1. The glasses are lightweight, easy to wear, inexpensive, and protect the eyes; however, they provide minimal magnification and do not compensate for differences in vision between both eyes.

Magnification Visor
The magnification visor is a headband visor with magnification lenses. It comes in various levels of magnification ranging from ×1.5 to ×3.5. It can be worn over prescription or safety glasses, may be pivoted out of the way when not in use, and is inexpensive. Conversely, it may be bulky to wear, cannot be customized, and does not offer the best resolution.

Magnification Clips
Magnification clips are hard-coated magnifying lens plates that fasten to eyeglass frames and range in level of magnification from ×1.5 to ×3.5. They can be pivoted out of the viewing angle, are lightweight, and are inexpensive; however, positioning may be difficult for ideal working distance and viewing angle.

Magnifier With Frame/Headband
The magnifier with frame is similar to magnification clips, but the magnification lens plate comes with a frame. It can be used with or without glasses and comes in magnification levels of ×1.5 to ×3.5. It is light, inexpensive, and may be pivoted out of sight, but similar to magnification clips, positioning for the right viewing angle and working distance may be difficult.

The magnifier with headband is essentially the same as the magnifier with frame. The only difference is the magnification plate is attached to a headband as opposed to a frame. It has similar benefits and limitations as the magnifier with frame.

Magnification Stand
The magnification stand comes as a large magnification lens with a flexible arm attached to a stand. It is a basic magnification tool and does not need to be worn; however, the stand is not easily portable and may be cumbersome to use.

Surgical Loupes
Surgical loupes are a robust magnification choice and the mainstay in magnification for the dermatologic surgeon. Loupes have proven to have comparable results in some procedures to the powerful operating surgical microscope.^14-17 Factors to consider with loupes include brand, design, lens, magnification, resolution, optimal working distance, field depth, and declination angle.¹⁸

The 2 surgical loupe designs—flip-up loupes and through-the-lens loupes—differ in the mounting of the optic lenses on safety glasses. Flip-up loupes have the optics mounted to the bridge of the frame, whereas through-the-lens loupes are fixed in the lenses.

There are 3 different optical systems for surgical loupe magnification: simple, compound, and prismatic. Simple lenses consist of one pair of positive meniscus lenses similar to reading glasses. Compound lenses are made of 2 magnification lenses. Prismatic lenses magnify using a prism that folds and lengthens the light path.^19,20

Loupes range in magnification level from ×2.5 to ×4.5. Compared to other magnification modalities, they can be customized and offer better resolution with quality magnification. Additionally, loupes can be fitted with a light source; however, they are expensive and surgeons need time to get used to the increased magnification as well as wearing the loupes.

There are advantages and disadvantages to the different loupe designs (Table 2). Flip-up loupes are more versatile, allowing for use on various safety glasses. They can be flipped out of view, and the declination angle may be altered; however, flip-up loupes have a narrower field of view and are heavier and bulkier than through-the-lens loupes. Through-the-lens loupes are lighter and have a larger field of view, as the optics are closer to the eye. They are customized to the declination angle and working distance of the surgeon. Conversely, through-the-lens loupes are more expensive and cannot be adjusted or moved from the line of vision.

Operating Surgical Microscope
The operating surgical microscope is not practical in the dermatologic surgeon’s practice. It is expensive and provides unnecessarily powerful magnification for dermatologic surgery. This tool usually is used in the operating room for suturing nerves and vessels with sutures sized 8-0 and smaller. Most skin procedures require size 6-0 and larger sutures.

Dermoscope
Dermoscopy, also known as epiluminescence microscopy, is a technique utilizing a handheld device made up of polarized light and a ×10 magnifying lens to evaluate skin lesions. In skilled hands, dermoscopy allows for the examination of characteristic patterns and morphologic features of skin lesions to enhance the clinician’s diagnostic accuracy.²¹ It may aid the dermatologic surgeon in identifying the surgical margins of difficult-to-define skin cancers. It is small and mobile; however, it has minimal benefit to the dermatologic surgeon during surgery because it is handheld and has a small field of view.

Conclusion

Good ergonomic practices facilitate a healthier and prolonged career for the dermatologic surgeon. When used properly, magnification devices can be a beneficial adjunct to the dermatologic surgeon by promoting better posture, preventing eyestrain, and providing enhanced visualization of the operating field and instruments. Use of magnification devices has been demonstrated to improve patient outcomes in other specialties. There are opportunities for further research specific to magnification improving dermatologic surgery outcomes given the high level of precision and accuracy needed for Mohs micrographic surgery, wound reconstruction, nail surgery, and hair transplantation.

Given the amount of time physicians spend entering data, clicking through screens, navigating pages, and logging in to computers, one would have hoped that substantial near-term payback for such efforts would have materialized.

Many of us believed this would take the form of health information exchange – the ability to easily access clinical information from hospitals or clinics other than our own, creating a more complete picture of the patient before us. To our disappointment, true information exchange has yet to materialize. (We won’t debate here whether politics or technology is culpable.) We are left to look elsewhere for the benefits of the digitization of the medical records and other sources of health care knowledge.

Lately, there has been a lot of talk about the promise of machine learning and artificial intelligence (AI) in health care. Much of the resurgence of interest in AI can be traced to IBM Watson’s appearance as a contestant on Jeopardy in 2011. Watson, a natural language supercomputer with enough power to process the equivalent of a million books per second, had access to 200 million pages of content, including the full text of Wikipedia, for Jeopardy.¹ Watson handily outperformed its human opponents – two Jeopardy savants who were also the most successful contestants in game show history – taking the $1 million first prize but struggling in categories with clues containing only a few words.
 

MD Anderson and Watson: Dashed hopes follow initial promise

As a result of growing recognition of AI’s potential in health care, IBM began collaborations with a number of health care organizations to deploy Watson.

In 2013, MD Anderson Cancer Center and IBM began a pilot to develop an oncology clinical decision support technology tool powered by Watson to aid MD Anderson “in its mission to eradicate cancer.” Recently, it was announced that the project – which cost the cancer center $62 million – has been put on hold, and MD Anderson is looking for other contractors to replace IBM.

While administrative problems are at least partly responsible for the project’s challenges, the undertaking has raised issues with the quality and quantity of data in health care that call into question the ability of AI to work as well in health care as it did on Jeopardy, at least in the short term.
 

Health care: Not as data rich as you might think

“We are not ‘Big Data’ in health care, yet.” – Dale Sanders, Health Catalyst.²

In its quest for Jeopardy victory, Watson accessed a massive data storehouse subsuming a vast array of knowledge assembled over the course of human history. Conversely, for health care, Watson is limited to a few decades of scientific journals (that may not contribute to diagnosis and treatment as much as one might think), claims data geared to billing without much clinical information like outcomes, and clinical data from progress notes (plagued by inaccuracies, serial “copy and paste,” and nonstandardized language and numeric representations), and variable-format reports from lab, radiology, pathology, and other disciplines.

To articulate how data-poor health care is, Dale Sanders, executive vice president for software at Health Catalyst, notes that a Boeing 787 generates 500GB of data in a six hour flight while one patient may generate just 100MB of data in an entire year.² He pointed out that, in the near term, AI platforms like Watson simply do not have enough data substrate to impact health care as many hoped it would. Over the longer term, he says, if health care can develop a coherent, standard approach to data content, AI may fulfill its promise.

SKapi/Thinkstock

What can AI and related technologies achieve in the near-term?

“AI seems to have replaced Uber as the most overused word or phrase in digital health.” – Reporter Stephanie Baum, paraphrasing from an interview with Bob Kocher, Venrock Partners.³

My observations tell me that we have already made some progress and are likely to make more strides in the coming years, thanks to AI, machine learning, and natural language processing. A few areas of potential gain are:

Clinical documentation

Technology that can derive meaning from words or groups of words can help with more accurate clinical documentation. For example, if a patient has a documented UTI but also has in the record an 11 on the Glasgow Coma Scale, a systolic BP of 90, and a respiratory rate of 24, technology can alert the physician to document sepsis.

Quality measurement and reporting

Similarly, if technology can recognize words and numbers, it may be able to extract and report quality measures (for example, an ejection fraction of 35% in a heart failure patient) from progress notes without having a nurse-abstractor manually enter such data into structured fields for reporting, as is currently the case.

Predicting readmissions, mortality, other events

While machine learning has had mixed results in predicting future clinical events, this is likely to change as data integrity and algorithms improve. Best-of-breed technology will probably use both clinical and machine learning tools for predictive purposes in the future.

In 2015, I had the privilege of meeting Vinod Khosla, cofounder of SUN Microsystems and venture capitalist, who predicts that computers will largely supplant physicians in the future, at least in domains relying on access to data. As he puts it, “the core functions necessary for complex diagnoses, treatments, and monitoring will be driven by machine judgment instead of human judgment.”⁴

While the benefits of technology, especially in health care, are often oversold, I believe AI and related technologies will some day play a large role alongside physicians in the care of patients. However, for AI to deliver, we must first figure out how to collect and organize health care data so that computers are able to ingest, digest and use it in a purposeful way.

Note: Dr. Whitcomb is founder and advisor to Zato Health, which uses natural language processing and discovery technology in health care.

He is chief medical officer at Remedy Partners in Darien, Conn., and a cofounder and past president of SHM.

References

1. Zimmer, Ben. Is It Time to Welcome Our New Computer Overlords?. The Atlantic. https://www.theatlantic.com/technology/archive/2011/02/is-it-time-to-welcome-our-new-computer-overlords/71388/. Accessed 23 Apr 2017.

2. Sanders, Dale. The MD Anderson / IBM Watson Announcement: What does it mean for machine learning in healthcare? Webinar. https://www.slideshare.net/healthcatalyst1/the-md-anderson-ibm-watson-announcement-what-does-it-mean-for-machine-learning-in-healthcare. Accessed 23 Apr 2017.

3. Baum, Stephanie. Venrock survey predicts a flight to quality for digital health investments. MedCity News. 12 Apr 2017. http://medcitynews.com/2017/04/venrock-survey-predicts-flight-quality-digital-health-investment/. Accessed 22 Apr 2017.

4. Khosla, Vinod. The Reinvention Of Medicine: Dr. Algorithm V0-7 And Beyond. TechCrunch. 22 Sept 2014. https://techcrunch.com/2014/09/22/the-reinvention-of-medicine-dr-algorithm-version-0-7-and-beyond/. Accessed 22 Apr 2017.

Given the amount of time physicians spend entering data, clicking through screens, navigating pages, and logging in to computers, one would have hoped that substantial near-term payback for such efforts would have materialized.

Many of us believed this would take the form of health information exchange – the ability to easily access clinical information from hospitals or clinics other than our own, creating a more complete picture of the patient before us. To our disappointment, true information exchange has yet to materialize. (We won’t debate here whether politics or technology is culpable.) We are left to look elsewhere for the benefits of the digitization of the medical records and other sources of health care knowledge.

Lately, there has been a lot of talk about the promise of machine learning and artificial intelligence (AI) in health care. Much of the resurgence of interest in AI can be traced to IBM Watson’s appearance as a contestant on Jeopardy in 2011. Watson, a natural language supercomputer with enough power to process the equivalent of a million books per second, had access to 200 million pages of content, including the full text of Wikipedia, for Jeopardy.¹ Watson handily outperformed its human opponents – two Jeopardy savants who were also the most successful contestants in game show history – taking the $1 million first prize but struggling in categories with clues containing only a few words.
 

MD Anderson and Watson: Dashed hopes follow initial promise

As a result of growing recognition of AI’s potential in health care, IBM began collaborations with a number of health care organizations to deploy Watson.

In 2013, MD Anderson Cancer Center and IBM began a pilot to develop an oncology clinical decision support technology tool powered by Watson to aid MD Anderson “in its mission to eradicate cancer.” Recently, it was announced that the project – which cost the cancer center $62 million – has been put on hold, and MD Anderson is looking for other contractors to replace IBM.

While administrative problems are at least partly responsible for the project’s challenges, the undertaking has raised issues with the quality and quantity of data in health care that call into question the ability of AI to work as well in health care as it did on Jeopardy, at least in the short term.
 

Health care: Not as data rich as you might think

“We are not ‘Big Data’ in health care, yet.” – Dale Sanders, Health Catalyst.²

In its quest for Jeopardy victory, Watson accessed a massive data storehouse subsuming a vast array of knowledge assembled over the course of human history. Conversely, for health care, Watson is limited to a few decades of scientific journals (that may not contribute to diagnosis and treatment as much as one might think), claims data geared to billing without much clinical information like outcomes, and clinical data from progress notes (plagued by inaccuracies, serial “copy and paste,” and nonstandardized language and numeric representations), and variable-format reports from lab, radiology, pathology, and other disciplines.

To articulate how data-poor health care is, Dale Sanders, executive vice president for software at Health Catalyst, notes that a Boeing 787 generates 500GB of data in a six hour flight while one patient may generate just 100MB of data in an entire year.² He pointed out that, in the near term, AI platforms like Watson simply do not have enough data substrate to impact health care as many hoped it would. Over the longer term, he says, if health care can develop a coherent, standard approach to data content, AI may fulfill its promise.

SKapi/Thinkstock

What can AI and related technologies achieve in the near-term?

“AI seems to have replaced Uber as the most overused word or phrase in digital health.” – Reporter Stephanie Baum, paraphrasing from an interview with Bob Kocher, Venrock Partners.³

My observations tell me that we have already made some progress and are likely to make more strides in the coming years, thanks to AI, machine learning, and natural language processing. A few areas of potential gain are:

Clinical documentation

Technology that can derive meaning from words or groups of words can help with more accurate clinical documentation. For example, if a patient has a documented UTI but also has in the record an 11 on the Glasgow Coma Scale, a systolic BP of 90, and a respiratory rate of 24, technology can alert the physician to document sepsis.

Quality measurement and reporting

Similarly, if technology can recognize words and numbers, it may be able to extract and report quality measures (for example, an ejection fraction of 35% in a heart failure patient) from progress notes without having a nurse-abstractor manually enter such data into structured fields for reporting, as is currently the case.

Predicting readmissions, mortality, other events

While machine learning has had mixed results in predicting future clinical events, this is likely to change as data integrity and algorithms improve. Best-of-breed technology will probably use both clinical and machine learning tools for predictive purposes in the future.

In 2015, I had the privilege of meeting Vinod Khosla, cofounder of SUN Microsystems and venture capitalist, who predicts that computers will largely supplant physicians in the future, at least in domains relying on access to data. As he puts it, “the core functions necessary for complex diagnoses, treatments, and monitoring will be driven by machine judgment instead of human judgment.”⁴

While the benefits of technology, especially in health care, are often oversold, I believe AI and related technologies will some day play a large role alongside physicians in the care of patients. However, for AI to deliver, we must first figure out how to collect and organize health care data so that computers are able to ingest, digest and use it in a purposeful way.

Note: Dr. Whitcomb is founder and advisor to Zato Health, which uses natural language processing and discovery technology in health care.

He is chief medical officer at Remedy Partners in Darien, Conn., and a cofounder and past president of SHM.

References

1. Zimmer, Ben. Is It Time to Welcome Our New Computer Overlords?. The Atlantic. https://www.theatlantic.com/technology/archive/2011/02/is-it-time-to-welcome-our-new-computer-overlords/71388/. Accessed 23 Apr 2017.

2. Sanders, Dale. The MD Anderson / IBM Watson Announcement: What does it mean for machine learning in healthcare? Webinar. https://www.slideshare.net/healthcatalyst1/the-md-anderson-ibm-watson-announcement-what-does-it-mean-for-machine-learning-in-healthcare. Accessed 23 Apr 2017.

3. Baum, Stephanie. Venrock survey predicts a flight to quality for digital health investments. MedCity News. 12 Apr 2017. http://medcitynews.com/2017/04/venrock-survey-predicts-flight-quality-digital-health-investment/. Accessed 22 Apr 2017.

4. Khosla, Vinod. The Reinvention Of Medicine: Dr. Algorithm V0-7 And Beyond. TechCrunch. 22 Sept 2014. https://techcrunch.com/2014/09/22/the-reinvention-of-medicine-dr-algorithm-version-0-7-and-beyond/. Accessed 22 Apr 2017.

Given the amount of time physicians spend entering data, clicking through screens, navigating pages, and logging in to computers, one would have hoped that substantial near-term payback for such efforts would have materialized.

Many of us believed this would take the form of health information exchange – the ability to easily access clinical information from hospitals or clinics other than our own, creating a more complete picture of the patient before us. To our disappointment, true information exchange has yet to materialize. (We won’t debate here whether politics or technology is culpable.) We are left to look elsewhere for the benefits of the digitization of the medical records and other sources of health care knowledge.

Lately, there has been a lot of talk about the promise of machine learning and artificial intelligence (AI) in health care. Much of the resurgence of interest in AI can be traced to IBM Watson’s appearance as a contestant on Jeopardy in 2011. Watson, a natural language supercomputer with enough power to process the equivalent of a million books per second, had access to 200 million pages of content, including the full text of Wikipedia, for Jeopardy.¹ Watson handily outperformed its human opponents – two Jeopardy savants who were also the most successful contestants in game show history – taking the $1 million first prize but struggling in categories with clues containing only a few words.
 

MD Anderson and Watson: Dashed hopes follow initial promise

As a result of growing recognition of AI’s potential in health care, IBM began collaborations with a number of health care organizations to deploy Watson.

In 2013, MD Anderson Cancer Center and IBM began a pilot to develop an oncology clinical decision support technology tool powered by Watson to aid MD Anderson “in its mission to eradicate cancer.” Recently, it was announced that the project – which cost the cancer center $62 million – has been put on hold, and MD Anderson is looking for other contractors to replace IBM.

While administrative problems are at least partly responsible for the project’s challenges, the undertaking has raised issues with the quality and quantity of data in health care that call into question the ability of AI to work as well in health care as it did on Jeopardy, at least in the short term.
 

Health care: Not as data rich as you might think

“We are not ‘Big Data’ in health care, yet.” – Dale Sanders, Health Catalyst.²

In its quest for Jeopardy victory, Watson accessed a massive data storehouse subsuming a vast array of knowledge assembled over the course of human history. Conversely, for health care, Watson is limited to a few decades of scientific journals (that may not contribute to diagnosis and treatment as much as one might think), claims data geared to billing without much clinical information like outcomes, and clinical data from progress notes (plagued by inaccuracies, serial “copy and paste,” and nonstandardized language and numeric representations), and variable-format reports from lab, radiology, pathology, and other disciplines.

To articulate how data-poor health care is, Dale Sanders, executive vice president for software at Health Catalyst, notes that a Boeing 787 generates 500GB of data in a six hour flight while one patient may generate just 100MB of data in an entire year.² He pointed out that, in the near term, AI platforms like Watson simply do not have enough data substrate to impact health care as many hoped it would. Over the longer term, he says, if health care can develop a coherent, standard approach to data content, AI may fulfill its promise.

SKapi/Thinkstock

What can AI and related technologies achieve in the near-term?

“AI seems to have replaced Uber as the most overused word or phrase in digital health.” – Reporter Stephanie Baum, paraphrasing from an interview with Bob Kocher, Venrock Partners.³

My observations tell me that we have already made some progress and are likely to make more strides in the coming years, thanks to AI, machine learning, and natural language processing. A few areas of potential gain are:

Clinical documentation

Technology that can derive meaning from words or groups of words can help with more accurate clinical documentation. For example, if a patient has a documented UTI but also has in the record an 11 on the Glasgow Coma Scale, a systolic BP of 90, and a respiratory rate of 24, technology can alert the physician to document sepsis.

Quality measurement and reporting

Similarly, if technology can recognize words and numbers, it may be able to extract and report quality measures (for example, an ejection fraction of 35% in a heart failure patient) from progress notes without having a nurse-abstractor manually enter such data into structured fields for reporting, as is currently the case.

Predicting readmissions, mortality, other events

While machine learning has had mixed results in predicting future clinical events, this is likely to change as data integrity and algorithms improve. Best-of-breed technology will probably use both clinical and machine learning tools for predictive purposes in the future.

In 2015, I had the privilege of meeting Vinod Khosla, cofounder of SUN Microsystems and venture capitalist, who predicts that computers will largely supplant physicians in the future, at least in domains relying on access to data. As he puts it, “the core functions necessary for complex diagnoses, treatments, and monitoring will be driven by machine judgment instead of human judgment.”⁴

While the benefits of technology, especially in health care, are often oversold, I believe AI and related technologies will some day play a large role alongside physicians in the care of patients. However, for AI to deliver, we must first figure out how to collect and organize health care data so that computers are able to ingest, digest and use it in a purposeful way.

Note: Dr. Whitcomb is founder and advisor to Zato Health, which uses natural language processing and discovery technology in health care.

He is chief medical officer at Remedy Partners in Darien, Conn., and a cofounder and past president of SHM.

References

1. Zimmer, Ben. Is It Time to Welcome Our New Computer Overlords?. The Atlantic. https://www.theatlantic.com/technology/archive/2011/02/is-it-time-to-welcome-our-new-computer-overlords/71388/. Accessed 23 Apr 2017.

2. Sanders, Dale. The MD Anderson / IBM Watson Announcement: What does it mean for machine learning in healthcare? Webinar. https://www.slideshare.net/healthcatalyst1/the-md-anderson-ibm-watson-announcement-what-does-it-mean-for-machine-learning-in-healthcare. Accessed 23 Apr 2017.

3. Baum, Stephanie. Venrock survey predicts a flight to quality for digital health investments. MedCity News. 12 Apr 2017. http://medcitynews.com/2017/04/venrock-survey-predicts-flight-quality-digital-health-investment/. Accessed 22 Apr 2017.

4. Khosla, Vinod. The Reinvention Of Medicine: Dr. Algorithm V0-7 And Beyond. TechCrunch. 22 Sept 2014. https://techcrunch.com/2014/09/22/the-reinvention-of-medicine-dr-algorithm-version-0-7-and-beyond/. Accessed 22 Apr 2017.

Arguably one of the most important public health issues in our nation is the gap between high-quality care and the people who need it most. The passage of the Affordable Care Act was meant, in part, to reduce this gap and increase health equity in terms of both eligibility for, and access to, care. However, lower-income residents, especially those from minority groups, are more likely to be hospitalized for asthma, hypertension, heart disease, and diabetes, and to experience infertility, preterm birth, and fetal death.

Health disparities, or inequities, translate not only into greater suffering for certain segments of the population, but also to significantly greater health care costs for everyone. Racial health disparities are associated with an estimated $35 billion annually in excess expenditures, $10 billion in lost productivity, and nearly $200 billion in premature deaths, according to an article in the Harvard Business Review. A 2013 study estimated that reducing racial disparities in adverse pregnancy outcomes – preeclampsia, preterm birth, gestational diabetes mellitus, and fetal death/stillbirth – could generate health care cost savings of up to $214 million per year (Matern Child Health J. 2013 Oct;17[8]:1518-25).

Several years ago, the State of Maryland took a unique approach to reducing health disparities by passing the Maryland Health Improvement and Disparities Reduction Act. One of the major components of this legislation was the creation of Health Enterprise Zones (HEZs), distinct geographical areas across the state dedicated to addressing health disparities and improving access to high-quality care. This incentive-based program provides state-funded resources to primary care providers and community-based health organizations specifically to help the neighborhoods they serve. I was deeply honored to serve as chairman of the task force that recommended the establishment of the HEZs.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

Arguably one of the most important public health issues in our nation is the gap between high-quality care and the people who need it most. The passage of the Affordable Care Act was meant, in part, to reduce this gap and increase health equity in terms of both eligibility for, and access to, care. However, lower-income residents, especially those from minority groups, are more likely to be hospitalized for asthma, hypertension, heart disease, and diabetes, and to experience infertility, preterm birth, and fetal death.

Health disparities, or inequities, translate not only into greater suffering for certain segments of the population, but also to significantly greater health care costs for everyone. Racial health disparities are associated with an estimated $35 billion annually in excess expenditures, $10 billion in lost productivity, and nearly $200 billion in premature deaths, according to an article in the Harvard Business Review. A 2013 study estimated that reducing racial disparities in adverse pregnancy outcomes – preeclampsia, preterm birth, gestational diabetes mellitus, and fetal death/stillbirth – could generate health care cost savings of up to $214 million per year (Matern Child Health J. 2013 Oct;17[8]:1518-25).

Several years ago, the State of Maryland took a unique approach to reducing health disparities by passing the Maryland Health Improvement and Disparities Reduction Act. One of the major components of this legislation was the creation of Health Enterprise Zones (HEZs), distinct geographical areas across the state dedicated to addressing health disparities and improving access to high-quality care. This incentive-based program provides state-funded resources to primary care providers and community-based health organizations specifically to help the neighborhoods they serve. I was deeply honored to serve as chairman of the task force that recommended the establishment of the HEZs.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

Arguably one of the most important public health issues in our nation is the gap between high-quality care and the people who need it most. The passage of the Affordable Care Act was meant, in part, to reduce this gap and increase health equity in terms of both eligibility for, and access to, care. However, lower-income residents, especially those from minority groups, are more likely to be hospitalized for asthma, hypertension, heart disease, and diabetes, and to experience infertility, preterm birth, and fetal death.

Health disparities, or inequities, translate not only into greater suffering for certain segments of the population, but also to significantly greater health care costs for everyone. Racial health disparities are associated with an estimated $35 billion annually in excess expenditures, $10 billion in lost productivity, and nearly $200 billion in premature deaths, according to an article in the Harvard Business Review. A 2013 study estimated that reducing racial disparities in adverse pregnancy outcomes – preeclampsia, preterm birth, gestational diabetes mellitus, and fetal death/stillbirth – could generate health care cost savings of up to $214 million per year (Matern Child Health J. 2013 Oct;17[8]:1518-25).

Several years ago, the State of Maryland took a unique approach to reducing health disparities by passing the Maryland Health Improvement and Disparities Reduction Act. One of the major components of this legislation was the creation of Health Enterprise Zones (HEZs), distinct geographical areas across the state dedicated to addressing health disparities and improving access to high-quality care. This incentive-based program provides state-funded resources to primary care providers and community-based health organizations specifically to help the neighborhoods they serve. I was deeply honored to serve as chairman of the task force that recommended the establishment of the HEZs.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

Of all the medical professions, obstetrics and gynecology should be the strongest champion for equity in women’s health in this country and globally. The question is, what does this mean in the reality of 2017 and moving forward in the 21st century? What does it mean in the context of our own practices and in the landscape of current policy and politics?

Finding answers to these questions requires both a deep understanding of the meaning of health equity and a willingness to rethink the architecture and engineering of how we currently provide care.

The terms equity and equality are sometimes used interchangeably, but they actually have quite different meanings. Imagine three women of different heights standing underneath the lowest branch of a tall apple tree. None of the three women are tall enough to pick an apple from the branch.

If we think about equality, we would assist each woman by giving her a box to stand on, and all three boxes would be the same size. This means that while the tallest woman will now be able to pick an apple, the medium-height woman may be able to touch but not pick the apple, and the shortest woman still may not be able to reach the apple at all.

However, if we think about equity, we’d acknowledge that each woman needs her own personalized box to be able to pick the apple. For instance, the shortest woman may need a box that is three times the height of the box used by the tallest woman.

Achieving true population health for all women requires that we similarly eliminate inequities by providing each patient with her own personalized care plan to help her reach and maintain her health.

Our practices

Provider bias and stereotyping can impact health care and health outcomes, and it is important that we work to prevent this in ourselves and in our staff. This means not making assumptions. It means really listening to our patients in ways that we may not have before.

Women who have experienced health inequity may have unique barriers to success. Therefore, we must listen for cues and inquire about our patients’ environment and circumstances, as well as their partnerships and support – or lack thereof. We should then acknowledge and communicate that certain social and environmental factors may impact our ability to achieve a desired outcome.

How can we impact the diet of a patient with gestational diabetes, for instance, if we have not adequately communicated what medical nutritional therapy means in the context of her own culture and ability to access food? If she lives in a food desert or has food insecurity or lives in a violence-ridden neighborhood that keeps her from going to a grocery store regularly, we must think outside the box. Ob.gyns. and their clinical care teams can work with women who have less access to nutritious foods, or who have certain cultural food staples, to suggest recipes and grocery lists that make sense with respect to the types of stores they shop in or their cultural preferences.

When it comes to cancer prevention and treatment, how can we expect a woman to be compliant with screening if we cannot help her understand that she can get screening services for free with her health insurance? How can we help a woman who has coverage for, or access to, free screening but then no funding or coverage for a diagnostic test or cancer treatment? How can we support a patient with abnormal cancer screening results who hasn’t followed up for months because she is afraid to leave home without her partner’s permission?

Such questions and circumstances often involve what we call “social determinants of health,” and they force us to rethink how we can better deliver and optimize care. Re-engineering our practices for health equity may involve employing a more diverse practice staff, linking patients with community resources, modifying our practice hours to align better with working women’s schedules, or finding creative ways to discern patients’ motivating factors and then piggyback on these factors.

We may also need to modify how we approach the number of return visits that we request of women so that follow-up care aligns better with their ability to leave work or find childcare. Simply put, we should strive to set up our patients for success, not failure.

We can pointedly ask patients about the kinds of information and support they want and need. We might ask, for instance: What do you need, and how can I work with you, so that you can effectively monitor and control your glucose levels? How can I work with you to help you get onto a trajectory to stop smoking? How can I help you better understand what tests and procedures are covered under your insurance plan, or whether you qualify for free services?

Patients with lower health literacy may need teach-back methods to validate understanding, or messaging that is more focused and limited at any one time. Self-efficacy through patient-centered education and support should be our goal.

Practices and clinics may also be able to adapt elements of the National Cancer Institute’s multicenter Patient Navigation Research Program, in which community health workers or other “patient navigators” address women’s personal barriers to the timely follow-up of abnormal breast and cervical cancer screening results. Patient navigation through this program and similar projects, including programs that we’ve adapted for different racial and ethnic communities in and around Chicago, has reduced or eliminated delays in diagnostic resolution of gynecologic cancer (Cancer. 2015 Nov 15;121[22]:4025-34, Breast Cancer Res Treat. 2016 Aug;158[3]:523-34, Am J Public Health. 2015 May;105[5]:e87-94).

The patient navigation model is increasingly being adapted and used in a variety of contexts outside of cancer care as well. In a postpartum patient navigation program that we tested at Northwestern University’s Medicaid-based outpatient clinic, a navigator was hired to communicate with patients and support them between delivery and completion of their postpartum care. Patients were reminded through calls and/or texts of their postpartum visits and of the benefits of breastfeeding, effective contraception, and other postpartum practices.

The demonstration project was impactful: Women who were enrolled in the program were more likely to return for postpartum care, to receive World Health Organization Tier 1 or 2 contraception, and to have postpartum screening and vaccinations, compared with women who received care before the program began (Obstet Gynecol. 2017 May;129[5]:925-33).

Connections to our patients will help us to achieve health equity. This includes connections between the primary care we provide and the specialty care our patients sometimes require, both inside and outside of our field. We may refer a patient to an oncology team, for instance, and in the process, unwittingly transfer her care such that other conditions that we’ve been managing – hypertension, depression, or diabetes – fall by the wayside.

Instead, we have to re-engineer our processes so that we maintain personalized connections back to these patients. For example, the referring ob.gyn. could develop and send to the oncologist or gynecologic-oncologist a care plan that includes the patient’s comorbid conditions and how they could be managed. This would allow for clearer communication.

Our communities

As ob.gyns., we have a common goal of championing health equity and true population health for every woman, regardless of whether she lives in rural, urban, or suburban America and regardless of whether she has conservative or liberal values. To do so, we must extend ourselves beyond our own practices.

In a committee opinion on Racial and Ethnic Disparities in Obstetrics and Gynecology, the American College of Obstetricians and Gynecologists advises that ob.gyns. take a number of actions to increase health equity. These include raising awareness about inequity and its effects on health outcomes, promoting quality improvement projects that target disparities, working with public health leadership, and helping recruit ob.gyns. and other health care providers from racial and ethnic minority groups (Obstet Gynecol 2015;126:e130-4).

In Chicago, where 1 out of 5 people lives in poverty and 1 out of 10 lives in deep poverty, we are still in our infancy in combating health inequities. However, with partnerships between academic institutions, departments of health, and other organizations across various sectors, we are beginning to move the needle on these entrenched health inequities.

For example, in 2007, there was a 60% difference in breast cancer mortality between black and white women in Chicago. This disparity sparked the development of the Metropolitan Chicago Breast Cancer Task Force and a series of on-the-ground patient navigator programs, along with several key policy changes and new state laws.

State actions included requiring quality reporting on mammography and increasing the Medicaid reimbursement rate for mammography to the Medicare rate. Nationally, beneficial changes were made to Medicare’s quality metrics and to the National Breast and Cervical Cancer Early Detection Program. All told, through a combination of studies and initiatives focused on improving knowledge, trust, access to care, and quality of care, we have been able to decrease the breast cancer mortality gap by 20%.

We also have a role to play in nurturing and developing a workforce that better aligns with our evolving demographics. This involves redesigning how we plant seeds of opportunity among high school students, undergraduates, and young medical students, and how we seek job applicants. Moreover, when we help people get to the next step in their careers, we need to make sure there is continuous support to retain them and help propel them to the next level.

We should think creatively to establish programs or launch initiatives that can help level the playing field for all women. For example, I created a Massive Open Online Course called “Career 911: Your Future Job in Medicine and Healthcare” as a free workforce development pipeline program. It is accessible on a global platform (https://www.coursera.org/learn/healthcarejobs) and is one example of how we as ob.gyns. can leverage our skills and resources.

Along the way, we also need to train our students and residents – and ourselves – to be more familiar with, and articulate about, health care policy. We need to understand how policy is made and modified and how we can be good communicators and thought leaders.

Right now, our ability to articulate our patients’ stories to policy makers and to the public seems underdeveloped and undertapped. The onus is on us to write and speak about how all women must have the opportunity to not only access care but to access high-quality care and preventive services that are important for full health. Providing health equity isn’t about giving someone a handout, but about giving her a helping hand to take control of her health.

Achieving health equity will involve changing our approach to research. If medical research on women’s health continues to be dominated by studies in which participants are homogeneous and from mainly white or well-resourced populations, we will never have output that is generalizable. As practicing ob.gyns., we can look for opportunities to advocate for diversity in research. We can also acknowledge that, for some women, there is historically-rooted distrust of the health care system that serves as a barrier both to obtaining care and enrolling in trials.

By meeting women where they are, and by tailoring their individual boxes as best we can – in research, in workforce development, and in clinical care delivery – we can work toward solutions.

Strategies for achieving women’s health equity

• Modify office hours/dates to allow flexibility for women who have challenges scheduling childcare and time off from work.

• Ensure handouts, educational materials, and all communications are at appropriate health literacy levels.

• Acknowledge and understand an individual woman’s barriers to care, including social determinants of health, and create a care plan that is achievable for her.

• Learn about and refer women to local community resources needed to overcome barriers to care, such as childcare, social services support, support services for intimate partner violence, and substance abuse counseling.

• Examine office processes to optimize the number of visits women have to attend for a particular health issue. Are there ways to explain results and next steps in a care plan without having to make her come back for an office visit?
 

Dr. Simon is the George H. Gardner Professor of Clinical Gynecology at Northwestern University, Chicago, and director of the Chicago Cancer Health Equity Collaborative. She is a member of the U.S. Preventive Services Task Force, but the views expressed in this piece are her own.

Of all the medical professions, obstetrics and gynecology should be the strongest champion for equity in women’s health in this country and globally. The question is, what does this mean in the reality of 2017 and moving forward in the 21st century? What does it mean in the context of our own practices and in the landscape of current policy and politics?

Finding answers to these questions requires both a deep understanding of the meaning of health equity and a willingness to rethink the architecture and engineering of how we currently provide care.

The terms equity and equality are sometimes used interchangeably, but they actually have quite different meanings. Imagine three women of different heights standing underneath the lowest branch of a tall apple tree. None of the three women are tall enough to pick an apple from the branch.

If we think about equality, we would assist each woman by giving her a box to stand on, and all three boxes would be the same size. This means that while the tallest woman will now be able to pick an apple, the medium-height woman may be able to touch but not pick the apple, and the shortest woman still may not be able to reach the apple at all.

However, if we think about equity, we’d acknowledge that each woman needs her own personalized box to be able to pick the apple. For instance, the shortest woman may need a box that is three times the height of the box used by the tallest woman.

Achieving true population health for all women requires that we similarly eliminate inequities by providing each patient with her own personalized care plan to help her reach and maintain her health.

Our practices

Provider bias and stereotyping can impact health care and health outcomes, and it is important that we work to prevent this in ourselves and in our staff. This means not making assumptions. It means really listening to our patients in ways that we may not have before.

Women who have experienced health inequity may have unique barriers to success. Therefore, we must listen for cues and inquire about our patients’ environment and circumstances, as well as their partnerships and support – or lack thereof. We should then acknowledge and communicate that certain social and environmental factors may impact our ability to achieve a desired outcome.

How can we impact the diet of a patient with gestational diabetes, for instance, if we have not adequately communicated what medical nutritional therapy means in the context of her own culture and ability to access food? If she lives in a food desert or has food insecurity or lives in a violence-ridden neighborhood that keeps her from going to a grocery store regularly, we must think outside the box. Ob.gyns. and their clinical care teams can work with women who have less access to nutritious foods, or who have certain cultural food staples, to suggest recipes and grocery lists that make sense with respect to the types of stores they shop in or their cultural preferences.

When it comes to cancer prevention and treatment, how can we expect a woman to be compliant with screening if we cannot help her understand that she can get screening services for free with her health insurance? How can we help a woman who has coverage for, or access to, free screening but then no funding or coverage for a diagnostic test or cancer treatment? How can we support a patient with abnormal cancer screening results who hasn’t followed up for months because she is afraid to leave home without her partner’s permission?

Such questions and circumstances often involve what we call “social determinants of health,” and they force us to rethink how we can better deliver and optimize care. Re-engineering our practices for health equity may involve employing a more diverse practice staff, linking patients with community resources, modifying our practice hours to align better with working women’s schedules, or finding creative ways to discern patients’ motivating factors and then piggyback on these factors.

We may also need to modify how we approach the number of return visits that we request of women so that follow-up care aligns better with their ability to leave work or find childcare. Simply put, we should strive to set up our patients for success, not failure.

We can pointedly ask patients about the kinds of information and support they want and need. We might ask, for instance: What do you need, and how can I work with you, so that you can effectively monitor and control your glucose levels? How can I work with you to help you get onto a trajectory to stop smoking? How can I help you better understand what tests and procedures are covered under your insurance plan, or whether you qualify for free services?

Patients with lower health literacy may need teach-back methods to validate understanding, or messaging that is more focused and limited at any one time. Self-efficacy through patient-centered education and support should be our goal.

Practices and clinics may also be able to adapt elements of the National Cancer Institute’s multicenter Patient Navigation Research Program, in which community health workers or other “patient navigators” address women’s personal barriers to the timely follow-up of abnormal breast and cervical cancer screening results. Patient navigation through this program and similar projects, including programs that we’ve adapted for different racial and ethnic communities in and around Chicago, has reduced or eliminated delays in diagnostic resolution of gynecologic cancer (Cancer. 2015 Nov 15;121[22]:4025-34, Breast Cancer Res Treat. 2016 Aug;158[3]:523-34, Am J Public Health. 2015 May;105[5]:e87-94).

The patient navigation model is increasingly being adapted and used in a variety of contexts outside of cancer care as well. In a postpartum patient navigation program that we tested at Northwestern University’s Medicaid-based outpatient clinic, a navigator was hired to communicate with patients and support them between delivery and completion of their postpartum care. Patients were reminded through calls and/or texts of their postpartum visits and of the benefits of breastfeeding, effective contraception, and other postpartum practices.

The demonstration project was impactful: Women who were enrolled in the program were more likely to return for postpartum care, to receive World Health Organization Tier 1 or 2 contraception, and to have postpartum screening and vaccinations, compared with women who received care before the program began (Obstet Gynecol. 2017 May;129[5]:925-33).

Connections to our patients will help us to achieve health equity. This includes connections between the primary care we provide and the specialty care our patients sometimes require, both inside and outside of our field. We may refer a patient to an oncology team, for instance, and in the process, unwittingly transfer her care such that other conditions that we’ve been managing – hypertension, depression, or diabetes – fall by the wayside.

Instead, we have to re-engineer our processes so that we maintain personalized connections back to these patients. For example, the referring ob.gyn. could develop and send to the oncologist or gynecologic-oncologist a care plan that includes the patient’s comorbid conditions and how they could be managed. This would allow for clearer communication.

Our communities

As ob.gyns., we have a common goal of championing health equity and true population health for every woman, regardless of whether she lives in rural, urban, or suburban America and regardless of whether she has conservative or liberal values. To do so, we must extend ourselves beyond our own practices.

In a committee opinion on Racial and Ethnic Disparities in Obstetrics and Gynecology, the American College of Obstetricians and Gynecologists advises that ob.gyns. take a number of actions to increase health equity. These include raising awareness about inequity and its effects on health outcomes, promoting quality improvement projects that target disparities, working with public health leadership, and helping recruit ob.gyns. and other health care providers from racial and ethnic minority groups (Obstet Gynecol 2015;126:e130-4).

In Chicago, where 1 out of 5 people lives in poverty and 1 out of 10 lives in deep poverty, we are still in our infancy in combating health inequities. However, with partnerships between academic institutions, departments of health, and other organizations across various sectors, we are beginning to move the needle on these entrenched health inequities.

For example, in 2007, there was a 60% difference in breast cancer mortality between black and white women in Chicago. This disparity sparked the development of the Metropolitan Chicago Breast Cancer Task Force and a series of on-the-ground patient navigator programs, along with several key policy changes and new state laws.

State actions included requiring quality reporting on mammography and increasing the Medicaid reimbursement rate for mammography to the Medicare rate. Nationally, beneficial changes were made to Medicare’s quality metrics and to the National Breast and Cervical Cancer Early Detection Program. All told, through a combination of studies and initiatives focused on improving knowledge, trust, access to care, and quality of care, we have been able to decrease the breast cancer mortality gap by 20%.

We also have a role to play in nurturing and developing a workforce that better aligns with our evolving demographics. This involves redesigning how we plant seeds of opportunity among high school students, undergraduates, and young medical students, and how we seek job applicants. Moreover, when we help people get to the next step in their careers, we need to make sure there is continuous support to retain them and help propel them to the next level.

We should think creatively to establish programs or launch initiatives that can help level the playing field for all women. For example, I created a Massive Open Online Course called “Career 911: Your Future Job in Medicine and Healthcare” as a free workforce development pipeline program. It is accessible on a global platform (https://www.coursera.org/learn/healthcarejobs) and is one example of how we as ob.gyns. can leverage our skills and resources.

Along the way, we also need to train our students and residents – and ourselves – to be more familiar with, and articulate about, health care policy. We need to understand how policy is made and modified and how we can be good communicators and thought leaders.

Right now, our ability to articulate our patients’ stories to policy makers and to the public seems underdeveloped and undertapped. The onus is on us to write and speak about how all women must have the opportunity to not only access care but to access high-quality care and preventive services that are important for full health. Providing health equity isn’t about giving someone a handout, but about giving her a helping hand to take control of her health.

Achieving health equity will involve changing our approach to research. If medical research on women’s health continues to be dominated by studies in which participants are homogeneous and from mainly white or well-resourced populations, we will never have output that is generalizable. As practicing ob.gyns., we can look for opportunities to advocate for diversity in research. We can also acknowledge that, for some women, there is historically-rooted distrust of the health care system that serves as a barrier both to obtaining care and enrolling in trials.

By meeting women where they are, and by tailoring their individual boxes as best we can – in research, in workforce development, and in clinical care delivery – we can work toward solutions.

Strategies for achieving women’s health equity

• Modify office hours/dates to allow flexibility for women who have challenges scheduling childcare and time off from work.

• Ensure handouts, educational materials, and all communications are at appropriate health literacy levels.

• Acknowledge and understand an individual woman’s barriers to care, including social determinants of health, and create a care plan that is achievable for her.

• Learn about and refer women to local community resources needed to overcome barriers to care, such as childcare, social services support, support services for intimate partner violence, and substance abuse counseling.

• Examine office processes to optimize the number of visits women have to attend for a particular health issue. Are there ways to explain results and next steps in a care plan without having to make her come back for an office visit?
 

Dr. Simon is the George H. Gardner Professor of Clinical Gynecology at Northwestern University, Chicago, and director of the Chicago Cancer Health Equity Collaborative. She is a member of the U.S. Preventive Services Task Force, but the views expressed in this piece are her own.

Of all the medical professions, obstetrics and gynecology should be the strongest champion for equity in women’s health in this country and globally. The question is, what does this mean in the reality of 2017 and moving forward in the 21st century? What does it mean in the context of our own practices and in the landscape of current policy and politics?

Finding answers to these questions requires both a deep understanding of the meaning of health equity and a willingness to rethink the architecture and engineering of how we currently provide care.

The terms equity and equality are sometimes used interchangeably, but they actually have quite different meanings. Imagine three women of different heights standing underneath the lowest branch of a tall apple tree. None of the three women are tall enough to pick an apple from the branch.

If we think about equality, we would assist each woman by giving her a box to stand on, and all three boxes would be the same size. This means that while the tallest woman will now be able to pick an apple, the medium-height woman may be able to touch but not pick the apple, and the shortest woman still may not be able to reach the apple at all.

However, if we think about equity, we’d acknowledge that each woman needs her own personalized box to be able to pick the apple. For instance, the shortest woman may need a box that is three times the height of the box used by the tallest woman.

Achieving true population health for all women requires that we similarly eliminate inequities by providing each patient with her own personalized care plan to help her reach and maintain her health.

Our practices

Provider bias and stereotyping can impact health care and health outcomes, and it is important that we work to prevent this in ourselves and in our staff. This means not making assumptions. It means really listening to our patients in ways that we may not have before.

Women who have experienced health inequity may have unique barriers to success. Therefore, we must listen for cues and inquire about our patients’ environment and circumstances, as well as their partnerships and support – or lack thereof. We should then acknowledge and communicate that certain social and environmental factors may impact our ability to achieve a desired outcome.

How can we impact the diet of a patient with gestational diabetes, for instance, if we have not adequately communicated what medical nutritional therapy means in the context of her own culture and ability to access food? If she lives in a food desert or has food insecurity or lives in a violence-ridden neighborhood that keeps her from going to a grocery store regularly, we must think outside the box. Ob.gyns. and their clinical care teams can work with women who have less access to nutritious foods, or who have certain cultural food staples, to suggest recipes and grocery lists that make sense with respect to the types of stores they shop in or their cultural preferences.

When it comes to cancer prevention and treatment, how can we expect a woman to be compliant with screening if we cannot help her understand that she can get screening services for free with her health insurance? How can we help a woman who has coverage for, or access to, free screening but then no funding or coverage for a diagnostic test or cancer treatment? How can we support a patient with abnormal cancer screening results who hasn’t followed up for months because she is afraid to leave home without her partner’s permission?

Such questions and circumstances often involve what we call “social determinants of health,” and they force us to rethink how we can better deliver and optimize care. Re-engineering our practices for health equity may involve employing a more diverse practice staff, linking patients with community resources, modifying our practice hours to align better with working women’s schedules, or finding creative ways to discern patients’ motivating factors and then piggyback on these factors.

We may also need to modify how we approach the number of return visits that we request of women so that follow-up care aligns better with their ability to leave work or find childcare. Simply put, we should strive to set up our patients for success, not failure.

We can pointedly ask patients about the kinds of information and support they want and need. We might ask, for instance: What do you need, and how can I work with you, so that you can effectively monitor and control your glucose levels? How can I work with you to help you get onto a trajectory to stop smoking? How can I help you better understand what tests and procedures are covered under your insurance plan, or whether you qualify for free services?

Patients with lower health literacy may need teach-back methods to validate understanding, or messaging that is more focused and limited at any one time. Self-efficacy through patient-centered education and support should be our goal.

Practices and clinics may also be able to adapt elements of the National Cancer Institute’s multicenter Patient Navigation Research Program, in which community health workers or other “patient navigators” address women’s personal barriers to the timely follow-up of abnormal breast and cervical cancer screening results. Patient navigation through this program and similar projects, including programs that we’ve adapted for different racial and ethnic communities in and around Chicago, has reduced or eliminated delays in diagnostic resolution of gynecologic cancer (Cancer. 2015 Nov 15;121[22]:4025-34, Breast Cancer Res Treat. 2016 Aug;158[3]:523-34, Am J Public Health. 2015 May;105[5]:e87-94).

The patient navigation model is increasingly being adapted and used in a variety of contexts outside of cancer care as well. In a postpartum patient navigation program that we tested at Northwestern University’s Medicaid-based outpatient clinic, a navigator was hired to communicate with patients and support them between delivery and completion of their postpartum care. Patients were reminded through calls and/or texts of their postpartum visits and of the benefits of breastfeeding, effective contraception, and other postpartum practices.

The demonstration project was impactful: Women who were enrolled in the program were more likely to return for postpartum care, to receive World Health Organization Tier 1 or 2 contraception, and to have postpartum screening and vaccinations, compared with women who received care before the program began (Obstet Gynecol. 2017 May;129[5]:925-33).

Connections to our patients will help us to achieve health equity. This includes connections between the primary care we provide and the specialty care our patients sometimes require, both inside and outside of our field. We may refer a patient to an oncology team, for instance, and in the process, unwittingly transfer her care such that other conditions that we’ve been managing – hypertension, depression, or diabetes – fall by the wayside.

Instead, we have to re-engineer our processes so that we maintain personalized connections back to these patients. For example, the referring ob.gyn. could develop and send to the oncologist or gynecologic-oncologist a care plan that includes the patient’s comorbid conditions and how they could be managed. This would allow for clearer communication.

Our communities

As ob.gyns., we have a common goal of championing health equity and true population health for every woman, regardless of whether she lives in rural, urban, or suburban America and regardless of whether she has conservative or liberal values. To do so, we must extend ourselves beyond our own practices.

In a committee opinion on Racial and Ethnic Disparities in Obstetrics and Gynecology, the American College of Obstetricians and Gynecologists advises that ob.gyns. take a number of actions to increase health equity. These include raising awareness about inequity and its effects on health outcomes, promoting quality improvement projects that target disparities, working with public health leadership, and helping recruit ob.gyns. and other health care providers from racial and ethnic minority groups (Obstet Gynecol 2015;126:e130-4).

In Chicago, where 1 out of 5 people lives in poverty and 1 out of 10 lives in deep poverty, we are still in our infancy in combating health inequities. However, with partnerships between academic institutions, departments of health, and other organizations across various sectors, we are beginning to move the needle on these entrenched health inequities.

For example, in 2007, there was a 60% difference in breast cancer mortality between black and white women in Chicago. This disparity sparked the development of the Metropolitan Chicago Breast Cancer Task Force and a series of on-the-ground patient navigator programs, along with several key policy changes and new state laws.

State actions included requiring quality reporting on mammography and increasing the Medicaid reimbursement rate for mammography to the Medicare rate. Nationally, beneficial changes were made to Medicare’s quality metrics and to the National Breast and Cervical Cancer Early Detection Program. All told, through a combination of studies and initiatives focused on improving knowledge, trust, access to care, and quality of care, we have been able to decrease the breast cancer mortality gap by 20%.

We also have a role to play in nurturing and developing a workforce that better aligns with our evolving demographics. This involves redesigning how we plant seeds of opportunity among high school students, undergraduates, and young medical students, and how we seek job applicants. Moreover, when we help people get to the next step in their careers, we need to make sure there is continuous support to retain them and help propel them to the next level.

We should think creatively to establish programs or launch initiatives that can help level the playing field for all women. For example, I created a Massive Open Online Course called “Career 911: Your Future Job in Medicine and Healthcare” as a free workforce development pipeline program. It is accessible on a global platform (https://www.coursera.org/learn/healthcarejobs) and is one example of how we as ob.gyns. can leverage our skills and resources.

Along the way, we also need to train our students and residents – and ourselves – to be more familiar with, and articulate about, health care policy. We need to understand how policy is made and modified and how we can be good communicators and thought leaders.

Right now, our ability to articulate our patients’ stories to policy makers and to the public seems underdeveloped and undertapped. The onus is on us to write and speak about how all women must have the opportunity to not only access care but to access high-quality care and preventive services that are important for full health. Providing health equity isn’t about giving someone a handout, but about giving her a helping hand to take control of her health.

Achieving health equity will involve changing our approach to research. If medical research on women’s health continues to be dominated by studies in which participants are homogeneous and from mainly white or well-resourced populations, we will never have output that is generalizable. As practicing ob.gyns., we can look for opportunities to advocate for diversity in research. We can also acknowledge that, for some women, there is historically-rooted distrust of the health care system that serves as a barrier both to obtaining care and enrolling in trials.

By meeting women where they are, and by tailoring their individual boxes as best we can – in research, in workforce development, and in clinical care delivery – we can work toward solutions.

Strategies for achieving women’s health equity

• Modify office hours/dates to allow flexibility for women who have challenges scheduling childcare and time off from work.

• Ensure handouts, educational materials, and all communications are at appropriate health literacy levels.

• Acknowledge and understand an individual woman’s barriers to care, including social determinants of health, and create a care plan that is achievable for her.

• Learn about and refer women to local community resources needed to overcome barriers to care, such as childcare, social services support, support services for intimate partner violence, and substance abuse counseling.

• Examine office processes to optimize the number of visits women have to attend for a particular health issue. Are there ways to explain results and next steps in a care plan without having to make her come back for an office visit?
 

Dr. Simon is the George H. Gardner Professor of Clinical Gynecology at Northwestern University, Chicago, and director of the Chicago Cancer Health Equity Collaborative. She is a member of the U.S. Preventive Services Task Force, but the views expressed in this piece are her own.

Hyperemesis gravidarum (HG) affects just 1%-2% of pregnant women, but it’s clinical consequences are significant, with excess vomiting and dehydration, hospitalization, and the need for intravenous fluids being common in that group. In extreme cases, repeated vomiting has led to tears in the esophagus and severe dehydration has caused acute renal failure. All of that leaves aside the obvious suffering and distress it causes for women with the condition.

While studies continue to support the long-held theory that mild-to-moderate nausea and vomiting has a protective effect in pregnancy, that does not appear to be true for HG. Rather, the medical literature shows that HG is associated with small-for-gestational-age neonates, low birth weight, higher rates of preterm birth, and lower Apgar scores at 5 minutes.

©monkeybusinessimages/thinkstockphotos.com

Dr. Koren is professor of physiology/pharmacology and pediatrics at Western University in Ontario. He is the founder of the Motherisk Program. Dr. Koren was a principal investigator in the U.S. study that resulted in the approval of Diclegis, marketed by Duchesnay USA, and has served as a consultant to Duchesnay.

Hyperemesis gravidarum (HG) affects just 1%-2% of pregnant women, but it’s clinical consequences are significant, with excess vomiting and dehydration, hospitalization, and the need for intravenous fluids being common in that group. In extreme cases, repeated vomiting has led to tears in the esophagus and severe dehydration has caused acute renal failure. All of that leaves aside the obvious suffering and distress it causes for women with the condition.

While studies continue to support the long-held theory that mild-to-moderate nausea and vomiting has a protective effect in pregnancy, that does not appear to be true for HG. Rather, the medical literature shows that HG is associated with small-for-gestational-age neonates, low birth weight, higher rates of preterm birth, and lower Apgar scores at 5 minutes.

©monkeybusinessimages/thinkstockphotos.com

Dr. Koren is professor of physiology/pharmacology and pediatrics at Western University in Ontario. He is the founder of the Motherisk Program. Dr. Koren was a principal investigator in the U.S. study that resulted in the approval of Diclegis, marketed by Duchesnay USA, and has served as a consultant to Duchesnay.

Hyperemesis gravidarum (HG) affects just 1%-2% of pregnant women, but it’s clinical consequences are significant, with excess vomiting and dehydration, hospitalization, and the need for intravenous fluids being common in that group. In extreme cases, repeated vomiting has led to tears in the esophagus and severe dehydration has caused acute renal failure. All of that leaves aside the obvious suffering and distress it causes for women with the condition.

While studies continue to support the long-held theory that mild-to-moderate nausea and vomiting has a protective effect in pregnancy, that does not appear to be true for HG. Rather, the medical literature shows that HG is associated with small-for-gestational-age neonates, low birth weight, higher rates of preterm birth, and lower Apgar scores at 5 minutes.

©monkeybusinessimages/thinkstockphotos.com

Dr. Koren is professor of physiology/pharmacology and pediatrics at Western University in Ontario. He is the founder of the Motherisk Program. Dr. Koren was a principal investigator in the U.S. study that resulted in the approval of Diclegis, marketed by Duchesnay USA, and has served as a consultant to Duchesnay.

Ovarian cancer remains the leading cause of death from gynecologic cancer worldwide and one of the five leading causes of death from cancer in women in the United States. In addition to surgery, treatment consists of combination platinum and taxane chemotherapy that offers a high response rate; however, a majority of women will develop persistent or recurrent disease.

A clinical practice statement released by the Society of Gynecologic Oncology in October 2014 states that “women diagnosed with epithelial ovarian, tubal, and peritoneal cancers should receive genetic counseling and be offered genetic testing, even in the absence of family history.” Patients should be informed that this genetic testing serves to prognosticate, inform about personal and familial cancer risk, but also aids in choices of novel therapeutic agents, specifically Poly (ADP-ribose) polymerase (PARP) inhibitors.

Genetic involvement of BRCA

A small proportion of ovarian cancers are attributable to genetic mutations, with approximately 10%-15% of cases caused by germline mutations of BRCA1 and BRCA2. BRCA1 deleterious mutations confer an ovarian cancer risk of approximately 39%-46%; and the risk of ovarian cancer is roughly 12%-20% for patients with BRCA2 deleterious mutations. As a tumor suppressor gene, BRCA is involved in the DNA repair process. Specifically, it is involved in homologous recombination (a form of double-stranded DNA repair mechanism). Thus, cells with defective BRCA proteins cannot repair double-stranded breaks (DSB) in DNA.

The homologous recombination pathway is complex and involves a number of genes. Deficiencies in this pathway confer a sensitivity to PARP inhibition. Tumors that share dysfunction in the homologous recombination pathway, but do not contain mutations in the BRCA gene, are classified as tumors with “BRCAness.”

Generally, the inheritance of a defective BRCA1 or BRCA2 allele (a germline mutation) alone is not enough to cause the development of cancer. Instead, once the second, functioning allele becomes nonfunctional, cancer can arise through an accumulation of mutations in the genetic code.

Furthermore, regardless of germline BRCA status, cancers have high rates of genetic mutation. As a result of the mutation rate, tumors can develop noninherited, noninheritable alterations in BRCA1 or BRCA2 genes (a somatic mutation).

Mechanism of PARP inhibitor activity

The PARP family of enzymes hold a vital role in the repair of DNA and the stabilization of the human genome through the repair of single-stranded breaks (SSB) in DNA. PARP inhibitors were originally developed as a chemosensitizing agent for other cytotoxic agents. It was only later discovered that ovarian cancer cells and mouse models that were deficient in BRCA proteins were especially sensitive to PARP inhibition. Eventually, the clinical development strategy became to employ PARP inhibitors in selected patients with BRCA mutations.

As previously mentioned, cells deficient in the tumor suppressor genes (BRCA1 and BRCA2) have an inability to repair DSBs. Inhibiting PARP enzymes will therefore cause an increase in SSB. During cell replication, these SSBs are converted to DSBs. Ultimately, the accumulation of DSBs leads to cell death. The concept that these two deficiencies – which alone are nonlethal – can be combined to induce cell death is described as synthetic lethality.

The exact mechanism through which PARP inhibitors function is not fully understood; however, four models currently exist to explain how PARP inhibitors instigate synthetic lethality. PARP inhibitors may block base excision repair mechanisms, trap PARP enzymes on damaged DNA, reduce the affinity of functioning BRCA enzymes to damaged DNA, and suppress nonhomologous end joining repair mechanisms.¹

FDA approval of PARP inhibitors

In recent years, the Food and Drug Administration has approved three PARP inhibitors in the treatment of ovarian cancer in slightly different clinical scenarios.

Olaparib was tested in a trial of 193 patients who harbored a deleterious or suspected deleterious germline BRCA-associated ovarian cancer who had received prior therapies.² Overall, the response rate in this population was 41% (95% confidence interval, 28-54) with a median duration of response of 8.0 months. These results led to the FDA approval of olaparib for ovarian cancer treatment as fourth-line therapy in patients with BRCA mutations.

Two separate trials using rucaparib showed an overall response rate of 54% and a duration of response of 9.2 months.^3,4 These early results allowed the FDA to grant accelerated approval to another PARP inhibitor for use in ovarian cancer.

More recently, a phase III trial of niraparib maintenance therapy versus placebo enrolled 553 women with recurrent epithelial ovarian cancer.⁵ Women with germline BRCA mutations had recurrence-free intervals of 21 months on niraparib, compared with 5.5 months for those on placebo. Even without germline BRCA mutations, women benefited from a recurrence-free interval of 9.3 months, compared with 3.9 months for placebo.

PARP inhibitors represent a novel targeted therapy for ovarian cancer, particularly those with deleterious germline or somatic BRCA mutations. When combined with genetic testing for BRCA mutations, PARP inhibitors represent an example of a predictive biomarker paired with a tailored therapeutic. Maturing data from ongoing trials will likely expand the opportunity to use PARP inhibitors for the treatment of ovarian cancer.
 

References

1. Br J Cancer. 2016 Nov 8;115(10):1157-73.

2. J Clin Oncol. 2015 Jan 20;33(3):244-50.

3. Clin Cancer Res. 2017 Mar 6. pii: clincanres.2796.2016. doi: 10.1158/1078-0432.CCR-16-2796.

4. Lancet Oncol. 2017 Jan;18(1):75-87.

5. N Engl J Med 2016; 375:2154-64.

Dr. Tran is a gynecologic oncology fellow in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at UNC-Chapel Hill. They reported having no relevant financial disclosures.

Ovarian cancer remains the leading cause of death from gynecologic cancer worldwide and one of the five leading causes of death from cancer in women in the United States. In addition to surgery, treatment consists of combination platinum and taxane chemotherapy that offers a high response rate; however, a majority of women will develop persistent or recurrent disease.

A clinical practice statement released by the Society of Gynecologic Oncology in October 2014 states that “women diagnosed with epithelial ovarian, tubal, and peritoneal cancers should receive genetic counseling and be offered genetic testing, even in the absence of family history.” Patients should be informed that this genetic testing serves to prognosticate, inform about personal and familial cancer risk, but also aids in choices of novel therapeutic agents, specifically Poly (ADP-ribose) polymerase (PARP) inhibitors.

Genetic involvement of BRCA

A small proportion of ovarian cancers are attributable to genetic mutations, with approximately 10%-15% of cases caused by germline mutations of BRCA1 and BRCA2. BRCA1 deleterious mutations confer an ovarian cancer risk of approximately 39%-46%; and the risk of ovarian cancer is roughly 12%-20% for patients with BRCA2 deleterious mutations. As a tumor suppressor gene, BRCA is involved in the DNA repair process. Specifically, it is involved in homologous recombination (a form of double-stranded DNA repair mechanism). Thus, cells with defective BRCA proteins cannot repair double-stranded breaks (DSB) in DNA.

The homologous recombination pathway is complex and involves a number of genes. Deficiencies in this pathway confer a sensitivity to PARP inhibition. Tumors that share dysfunction in the homologous recombination pathway, but do not contain mutations in the BRCA gene, are classified as tumors with “BRCAness.”

Generally, the inheritance of a defective BRCA1 or BRCA2 allele (a germline mutation) alone is not enough to cause the development of cancer. Instead, once the second, functioning allele becomes nonfunctional, cancer can arise through an accumulation of mutations in the genetic code.

Furthermore, regardless of germline BRCA status, cancers have high rates of genetic mutation. As a result of the mutation rate, tumors can develop noninherited, noninheritable alterations in BRCA1 or BRCA2 genes (a somatic mutation).

Mechanism of PARP inhibitor activity

The PARP family of enzymes hold a vital role in the repair of DNA and the stabilization of the human genome through the repair of single-stranded breaks (SSB) in DNA. PARP inhibitors were originally developed as a chemosensitizing agent for other cytotoxic agents. It was only later discovered that ovarian cancer cells and mouse models that were deficient in BRCA proteins were especially sensitive to PARP inhibition. Eventually, the clinical development strategy became to employ PARP inhibitors in selected patients with BRCA mutations.

As previously mentioned, cells deficient in the tumor suppressor genes (BRCA1 and BRCA2) have an inability to repair DSBs. Inhibiting PARP enzymes will therefore cause an increase in SSB. During cell replication, these SSBs are converted to DSBs. Ultimately, the accumulation of DSBs leads to cell death. The concept that these two deficiencies – which alone are nonlethal – can be combined to induce cell death is described as synthetic lethality.

The exact mechanism through which PARP inhibitors function is not fully understood; however, four models currently exist to explain how PARP inhibitors instigate synthetic lethality. PARP inhibitors may block base excision repair mechanisms, trap PARP enzymes on damaged DNA, reduce the affinity of functioning BRCA enzymes to damaged DNA, and suppress nonhomologous end joining repair mechanisms.¹

FDA approval of PARP inhibitors

In recent years, the Food and Drug Administration has approved three PARP inhibitors in the treatment of ovarian cancer in slightly different clinical scenarios.

Olaparib was tested in a trial of 193 patients who harbored a deleterious or suspected deleterious germline BRCA-associated ovarian cancer who had received prior therapies.² Overall, the response rate in this population was 41% (95% confidence interval, 28-54) with a median duration of response of 8.0 months. These results led to the FDA approval of olaparib for ovarian cancer treatment as fourth-line therapy in patients with BRCA mutations.

Two separate trials using rucaparib showed an overall response rate of 54% and a duration of response of 9.2 months.^3,4 These early results allowed the FDA to grant accelerated approval to another PARP inhibitor for use in ovarian cancer.

More recently, a phase III trial of niraparib maintenance therapy versus placebo enrolled 553 women with recurrent epithelial ovarian cancer.⁵ Women with germline BRCA mutations had recurrence-free intervals of 21 months on niraparib, compared with 5.5 months for those on placebo. Even without germline BRCA mutations, women benefited from a recurrence-free interval of 9.3 months, compared with 3.9 months for placebo.

PARP inhibitors represent a novel targeted therapy for ovarian cancer, particularly those with deleterious germline or somatic BRCA mutations. When combined with genetic testing for BRCA mutations, PARP inhibitors represent an example of a predictive biomarker paired with a tailored therapeutic. Maturing data from ongoing trials will likely expand the opportunity to use PARP inhibitors for the treatment of ovarian cancer.
 

References

1. Br J Cancer. 2016 Nov 8;115(10):1157-73.

2. J Clin Oncol. 2015 Jan 20;33(3):244-50.

3. Clin Cancer Res. 2017 Mar 6. pii: clincanres.2796.2016. doi: 10.1158/1078-0432.CCR-16-2796.

4. Lancet Oncol. 2017 Jan;18(1):75-87.

5. N Engl J Med 2016; 375:2154-64.

Dr. Tran is a gynecologic oncology fellow in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at UNC-Chapel Hill. They reported having no relevant financial disclosures.

Ovarian cancer remains the leading cause of death from gynecologic cancer worldwide and one of the five leading causes of death from cancer in women in the United States. In addition to surgery, treatment consists of combination platinum and taxane chemotherapy that offers a high response rate; however, a majority of women will develop persistent or recurrent disease.

A clinical practice statement released by the Society of Gynecologic Oncology in October 2014 states that “women diagnosed with epithelial ovarian, tubal, and peritoneal cancers should receive genetic counseling and be offered genetic testing, even in the absence of family history.” Patients should be informed that this genetic testing serves to prognosticate, inform about personal and familial cancer risk, but also aids in choices of novel therapeutic agents, specifically Poly (ADP-ribose) polymerase (PARP) inhibitors.

Genetic involvement of BRCA

A small proportion of ovarian cancers are attributable to genetic mutations, with approximately 10%-15% of cases caused by germline mutations of BRCA1 and BRCA2. BRCA1 deleterious mutations confer an ovarian cancer risk of approximately 39%-46%; and the risk of ovarian cancer is roughly 12%-20% for patients with BRCA2 deleterious mutations. As a tumor suppressor gene, BRCA is involved in the DNA repair process. Specifically, it is involved in homologous recombination (a form of double-stranded DNA repair mechanism). Thus, cells with defective BRCA proteins cannot repair double-stranded breaks (DSB) in DNA.

The homologous recombination pathway is complex and involves a number of genes. Deficiencies in this pathway confer a sensitivity to PARP inhibition. Tumors that share dysfunction in the homologous recombination pathway, but do not contain mutations in the BRCA gene, are classified as tumors with “BRCAness.”

Generally, the inheritance of a defective BRCA1 or BRCA2 allele (a germline mutation) alone is not enough to cause the development of cancer. Instead, once the second, functioning allele becomes nonfunctional, cancer can arise through an accumulation of mutations in the genetic code.

Furthermore, regardless of germline BRCA status, cancers have high rates of genetic mutation. As a result of the mutation rate, tumors can develop noninherited, noninheritable alterations in BRCA1 or BRCA2 genes (a somatic mutation).

Mechanism of PARP inhibitor activity

The PARP family of enzymes hold a vital role in the repair of DNA and the stabilization of the human genome through the repair of single-stranded breaks (SSB) in DNA. PARP inhibitors were originally developed as a chemosensitizing agent for other cytotoxic agents. It was only later discovered that ovarian cancer cells and mouse models that were deficient in BRCA proteins were especially sensitive to PARP inhibition. Eventually, the clinical development strategy became to employ PARP inhibitors in selected patients with BRCA mutations.

As previously mentioned, cells deficient in the tumor suppressor genes (BRCA1 and BRCA2) have an inability to repair DSBs. Inhibiting PARP enzymes will therefore cause an increase in SSB. During cell replication, these SSBs are converted to DSBs. Ultimately, the accumulation of DSBs leads to cell death. The concept that these two deficiencies – which alone are nonlethal – can be combined to induce cell death is described as synthetic lethality.

The exact mechanism through which PARP inhibitors function is not fully understood; however, four models currently exist to explain how PARP inhibitors instigate synthetic lethality. PARP inhibitors may block base excision repair mechanisms, trap PARP enzymes on damaged DNA, reduce the affinity of functioning BRCA enzymes to damaged DNA, and suppress nonhomologous end joining repair mechanisms.¹

FDA approval of PARP inhibitors

In recent years, the Food and Drug Administration has approved three PARP inhibitors in the treatment of ovarian cancer in slightly different clinical scenarios.

Olaparib was tested in a trial of 193 patients who harbored a deleterious or suspected deleterious germline BRCA-associated ovarian cancer who had received prior therapies.² Overall, the response rate in this population was 41% (95% confidence interval, 28-54) with a median duration of response of 8.0 months. These results led to the FDA approval of olaparib for ovarian cancer treatment as fourth-line therapy in patients with BRCA mutations.

Two separate trials using rucaparib showed an overall response rate of 54% and a duration of response of 9.2 months.^3,4 These early results allowed the FDA to grant accelerated approval to another PARP inhibitor for use in ovarian cancer.

More recently, a phase III trial of niraparib maintenance therapy versus placebo enrolled 553 women with recurrent epithelial ovarian cancer.⁵ Women with germline BRCA mutations had recurrence-free intervals of 21 months on niraparib, compared with 5.5 months for those on placebo. Even without germline BRCA mutations, women benefited from a recurrence-free interval of 9.3 months, compared with 3.9 months for placebo.

PARP inhibitors represent a novel targeted therapy for ovarian cancer, particularly those with deleterious germline or somatic BRCA mutations. When combined with genetic testing for BRCA mutations, PARP inhibitors represent an example of a predictive biomarker paired with a tailored therapeutic. Maturing data from ongoing trials will likely expand the opportunity to use PARP inhibitors for the treatment of ovarian cancer.
 

References

1. Br J Cancer. 2016 Nov 8;115(10):1157-73.

2. J Clin Oncol. 2015 Jan 20;33(3):244-50.

3. Clin Cancer Res. 2017 Mar 6. pii: clincanres.2796.2016. doi: 10.1158/1078-0432.CCR-16-2796.

4. Lancet Oncol. 2017 Jan;18(1):75-87.

5. N Engl J Med 2016; 375:2154-64.

Dr. Tran is a gynecologic oncology fellow in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at UNC-Chapel Hill. They reported having no relevant financial disclosures.

Editor’s Note: This is the fifth installment of a six-part series that will review key concepts and articles that ob.gyns. can use to prepare for the American Board of Obstetrics and Gynecology Maintenance of Certification examination. The series is adapted from Ob/Gyn Board Master (obgynboardmaster.com), an online board review course created by Erudyte. This month’s edition of the Board Corner focuses on pelvic organ prolapse.

The American College of Obstetricians and Gynecologists’ “Practice Bulletins” are important practice management guidelines for ob.gyn. clinicians. The Practice Bulletins are rich sources of material that is often tested on board exams. Earlier this year, ACOG released a revised Practice Bulletin (#176) updating its advice on the diagnosis and management of pelvic organ prolapse (POP).¹ It is a well-written document summarizing most of the landmark articles published in the field of female pelvic medicine and reconstructive surgery. We recommend you read this bulletin and review this topic carefully.

Let’s begin with a possible medical board question: Which of the following procedures is the most effective for a sexually-active patient with advanced prolapse?

A. Sacrospinous ligament suspension (SSLS)

B. Uterosacral ligament suspension (USLS)

C. Sacrocolpopexy (SCP)

D. Colpocleisis

E. Hysteropexy

Key points

The key points to remember are:

1. SCP is the most effective prolapse repair technique.

2. USLS and SSLS fixation are equally effective when compared with one another.

3. Colpocleisis is a highly successful procedure for POP in patients who are not sexually active.

Literature summary

The lifetime risk for undergoing surgery for POP or stress incontinence is 20%. POP is the descent of one or more aspects of the vagina or uterus, which allows nearby organs to herniate into the vagina. POP should only be treated if it is symptomatic and bothersome for the patient. The pessary is an alternative to surgical treatment of prolapse.

Proven risk factors for POP are increased parity, vaginal delivery, age, obesity, chronic constipation, and certain congenital anomalies. A history should be taken to elucidate symptoms of prolapse, such as bulge, pressure, sexual dysfunction, lower urinary tract dysfunction, or defecatory dysfunction. It is also important to find out how much the POP is affecting her quality of life. A physical exam is best performed with a split speculum, with bladder empty, while the patient performs a Valsalva maneuver. We recommend using the POP-Q system to grade the severity of prolapse. The tone of the pelvic floor muscle should also be evaluated (absent, weak, normal, or strong) during pelvic exam.

The minimum testing necessary for a patient with POP is urinalysis and a postvoid residual. A stress test with a full bladder should also be done with and without reduction of the prolapse. If you’re considering surgery and the patient has advanced prolapse and/or other complicating factors – such as obstructive symptoms or significant neurologic disorder – you should consider performing urodynamic testing as well.

Native tissue, suture-based reconstructive repairs of the vagina include apical procedures, such as SSLS and USLS, in addition to anterior colporrhaphy and posterior repair. At 2-year follow-up, SSLS and USLS along with anterior colporrhaphy and posterior repair are equally effective for treatment of prolapse with comparable functional and adverse outcomes. SCP is more effective than SSLS but the abdominal procedure (not laparoscopic) may be associated with more complications. Currently, there are no published randomized trials comparing minimally-invasive SCP to USLS, but one is underway (clinicaltrials.gov).

Other procedures for POP include obliterative procedures such as colpocleisis, which is highly effective for patients who do not desire future vaginal intercourse and also has low morbidity. Preservation of the uterus by hysteropexy procedures (either transvaginal or transabdominal) are also options for women desiring to preserve their uterus, but these procedures have little safety and efficacy data. Regardless of the procedure performed, routine intraoperative cystoscopy should be done to assure ureteral patency and to rule out injury to the lower urinary tract.

Some type of prophylactic anti-incontinence procedure – retropubic or Burch – may be done at the time of vaginal prolapse repair or abdominal prolapse repair, respectively, in order to reduce the chance of postoperative stress urinary incontinence in a patient without symptoms of stress incontinence. The exception to this is in a patient who has an elevated postvoid residual or someone with a prior anti-incontinence procedure without symptoms of stress urinary incontinence.

Practice tips

Finally, here are some precautions and words of advice about the following POP procedures:

• Neither synthetic nor biologic grafts should be used to augment posterior repairs as these do not improve outcomes.
• Transvaginal repair of rectocele is superior to the transanal repair techniques.
• Synthetic mesh augmentation of the anterior vaginal wall may improve anatomic outcomes, but this comes at a cost (more reoperations and higher rate of complications). Thus, surgeons performing these procedures should have specialized training and the patient should have a unique indication and must undergo proper consent as recommended by ACOG.

Dr. Siddighi is editor-in-chief of the Ob/Gyn Board Master and director of female pelvic medicine and reconstructive surgery and director of grand rounds at Loma Linda University Health in California. Ob.Gyn. News and Ob/Gyn Board Master are owned by the same parent company, Frontline Medical Communications.

Reference

1. Obstet Gynecol. 2017 Apr;129(4):e56-e72.

Editor’s Note: This is the fifth installment of a six-part series that will review key concepts and articles that ob.gyns. can use to prepare for the American Board of Obstetrics and Gynecology Maintenance of Certification examination. The series is adapted from Ob/Gyn Board Master (obgynboardmaster.com), an online board review course created by Erudyte. This month’s edition of the Board Corner focuses on pelvic organ prolapse.

The American College of Obstetricians and Gynecologists’ “Practice Bulletins” are important practice management guidelines for ob.gyn. clinicians. The Practice Bulletins are rich sources of material that is often tested on board exams. Earlier this year, ACOG released a revised Practice Bulletin (#176) updating its advice on the diagnosis and management of pelvic organ prolapse (POP).¹ It is a well-written document summarizing most of the landmark articles published in the field of female pelvic medicine and reconstructive surgery. We recommend you read this bulletin and review this topic carefully.

Let’s begin with a possible medical board question: Which of the following procedures is the most effective for a sexually-active patient with advanced prolapse?

A. Sacrospinous ligament suspension (SSLS)

B. Uterosacral ligament suspension (USLS)

C. Sacrocolpopexy (SCP)

D. Colpocleisis

E. Hysteropexy

Key points

The key points to remember are:

1. SCP is the most effective prolapse repair technique.

2. USLS and SSLS fixation are equally effective when compared with one another.

3. Colpocleisis is a highly successful procedure for POP in patients who are not sexually active.

Literature summary

The lifetime risk for undergoing surgery for POP or stress incontinence is 20%. POP is the descent of one or more aspects of the vagina or uterus, which allows nearby organs to herniate into the vagina. POP should only be treated if it is symptomatic and bothersome for the patient. The pessary is an alternative to surgical treatment of prolapse.

Proven risk factors for POP are increased parity, vaginal delivery, age, obesity, chronic constipation, and certain congenital anomalies. A history should be taken to elucidate symptoms of prolapse, such as bulge, pressure, sexual dysfunction, lower urinary tract dysfunction, or defecatory dysfunction. It is also important to find out how much the POP is affecting her quality of life. A physical exam is best performed with a split speculum, with bladder empty, while the patient performs a Valsalva maneuver. We recommend using the POP-Q system to grade the severity of prolapse. The tone of the pelvic floor muscle should also be evaluated (absent, weak, normal, or strong) during pelvic exam.

The minimum testing necessary for a patient with POP is urinalysis and a postvoid residual. A stress test with a full bladder should also be done with and without reduction of the prolapse. If you’re considering surgery and the patient has advanced prolapse and/or other complicating factors – such as obstructive symptoms or significant neurologic disorder – you should consider performing urodynamic testing as well.

Native tissue, suture-based reconstructive repairs of the vagina include apical procedures, such as SSLS and USLS, in addition to anterior colporrhaphy and posterior repair. At 2-year follow-up, SSLS and USLS along with anterior colporrhaphy and posterior repair are equally effective for treatment of prolapse with comparable functional and adverse outcomes. SCP is more effective than SSLS but the abdominal procedure (not laparoscopic) may be associated with more complications. Currently, there are no published randomized trials comparing minimally-invasive SCP to USLS, but one is underway (clinicaltrials.gov).

Other procedures for POP include obliterative procedures such as colpocleisis, which is highly effective for patients who do not desire future vaginal intercourse and also has low morbidity. Preservation of the uterus by hysteropexy procedures (either transvaginal or transabdominal) are also options for women desiring to preserve their uterus, but these procedures have little safety and efficacy data. Regardless of the procedure performed, routine intraoperative cystoscopy should be done to assure ureteral patency and to rule out injury to the lower urinary tract.

Some type of prophylactic anti-incontinence procedure – retropubic or Burch – may be done at the time of vaginal prolapse repair or abdominal prolapse repair, respectively, in order to reduce the chance of postoperative stress urinary incontinence in a patient without symptoms of stress incontinence. The exception to this is in a patient who has an elevated postvoid residual or someone with a prior anti-incontinence procedure without symptoms of stress urinary incontinence.

Practice tips

Finally, here are some precautions and words of advice about the following POP procedures:

• Neither synthetic nor biologic grafts should be used to augment posterior repairs as these do not improve outcomes.
• Transvaginal repair of rectocele is superior to the transanal repair techniques.
• Synthetic mesh augmentation of the anterior vaginal wall may improve anatomic outcomes, but this comes at a cost (more reoperations and higher rate of complications). Thus, surgeons performing these procedures should have specialized training and the patient should have a unique indication and must undergo proper consent as recommended by ACOG.

Dr. Siddighi is editor-in-chief of the Ob/Gyn Board Master and director of female pelvic medicine and reconstructive surgery and director of grand rounds at Loma Linda University Health in California. Ob.Gyn. News and Ob/Gyn Board Master are owned by the same parent company, Frontline Medical Communications.

Reference

1. Obstet Gynecol. 2017 Apr;129(4):e56-e72.

Editor’s Note: This is the fifth installment of a six-part series that will review key concepts and articles that ob.gyns. can use to prepare for the American Board of Obstetrics and Gynecology Maintenance of Certification examination. The series is adapted from Ob/Gyn Board Master (obgynboardmaster.com), an online board review course created by Erudyte. This month’s edition of the Board Corner focuses on pelvic organ prolapse.

The American College of Obstetricians and Gynecologists’ “Practice Bulletins” are important practice management guidelines for ob.gyn. clinicians. The Practice Bulletins are rich sources of material that is often tested on board exams. Earlier this year, ACOG released a revised Practice Bulletin (#176) updating its advice on the diagnosis and management of pelvic organ prolapse (POP).¹ It is a well-written document summarizing most of the landmark articles published in the field of female pelvic medicine and reconstructive surgery. We recommend you read this bulletin and review this topic carefully.

Let’s begin with a possible medical board question: Which of the following procedures is the most effective for a sexually-active patient with advanced prolapse?

A. Sacrospinous ligament suspension (SSLS)

B. Uterosacral ligament suspension (USLS)

C. Sacrocolpopexy (SCP)

D. Colpocleisis

E. Hysteropexy

Key points

The key points to remember are:

1. SCP is the most effective prolapse repair technique.

2. USLS and SSLS fixation are equally effective when compared with one another.

3. Colpocleisis is a highly successful procedure for POP in patients who are not sexually active.

Literature summary

The lifetime risk for undergoing surgery for POP or stress incontinence is 20%. POP is the descent of one or more aspects of the vagina or uterus, which allows nearby organs to herniate into the vagina. POP should only be treated if it is symptomatic and bothersome for the patient. The pessary is an alternative to surgical treatment of prolapse.

Proven risk factors for POP are increased parity, vaginal delivery, age, obesity, chronic constipation, and certain congenital anomalies. A history should be taken to elucidate symptoms of prolapse, such as bulge, pressure, sexual dysfunction, lower urinary tract dysfunction, or defecatory dysfunction. It is also important to find out how much the POP is affecting her quality of life. A physical exam is best performed with a split speculum, with bladder empty, while the patient performs a Valsalva maneuver. We recommend using the POP-Q system to grade the severity of prolapse. The tone of the pelvic floor muscle should also be evaluated (absent, weak, normal, or strong) during pelvic exam.

The minimum testing necessary for a patient with POP is urinalysis and a postvoid residual. A stress test with a full bladder should also be done with and without reduction of the prolapse. If you’re considering surgery and the patient has advanced prolapse and/or other complicating factors – such as obstructive symptoms or significant neurologic disorder – you should consider performing urodynamic testing as well.

Native tissue, suture-based reconstructive repairs of the vagina include apical procedures, such as SSLS and USLS, in addition to anterior colporrhaphy and posterior repair. At 2-year follow-up, SSLS and USLS along with anterior colporrhaphy and posterior repair are equally effective for treatment of prolapse with comparable functional and adverse outcomes. SCP is more effective than SSLS but the abdominal procedure (not laparoscopic) may be associated with more complications. Currently, there are no published randomized trials comparing minimally-invasive SCP to USLS, but one is underway (clinicaltrials.gov).

Other procedures for POP include obliterative procedures such as colpocleisis, which is highly effective for patients who do not desire future vaginal intercourse and also has low morbidity. Preservation of the uterus by hysteropexy procedures (either transvaginal or transabdominal) are also options for women desiring to preserve their uterus, but these procedures have little safety and efficacy data. Regardless of the procedure performed, routine intraoperative cystoscopy should be done to assure ureteral patency and to rule out injury to the lower urinary tract.

Some type of prophylactic anti-incontinence procedure – retropubic or Burch – may be done at the time of vaginal prolapse repair or abdominal prolapse repair, respectively, in order to reduce the chance of postoperative stress urinary incontinence in a patient without symptoms of stress incontinence. The exception to this is in a patient who has an elevated postvoid residual or someone with a prior anti-incontinence procedure without symptoms of stress urinary incontinence.

Practice tips

Finally, here are some precautions and words of advice about the following POP procedures:

• Neither synthetic nor biologic grafts should be used to augment posterior repairs as these do not improve outcomes.
• Transvaginal repair of rectocele is superior to the transanal repair techniques.
• Synthetic mesh augmentation of the anterior vaginal wall may improve anatomic outcomes, but this comes at a cost (more reoperations and higher rate of complications). Thus, surgeons performing these procedures should have specialized training and the patient should have a unique indication and must undergo proper consent as recommended by ACOG.

Dr. Siddighi is editor-in-chief of the Ob/Gyn Board Master and director of female pelvic medicine and reconstructive surgery and director of grand rounds at Loma Linda University Health in California. Ob.Gyn. News and Ob/Gyn Board Master are owned by the same parent company, Frontline Medical Communications.

Reference

1. Obstet Gynecol. 2017 Apr;129(4):e56-e72.

Treatment Before, During, and After Pregnancy

To evaluate treatment patterns before, during, and after pregnancy in women with MS and a live birth, Dr. Houtchens and colleagues used a US administrative claims database to conduct a retrospective analysis of women ages 18 to 65 with MS, a claim indicative of a live birth, and one-year continuous eligibility before and after pregnancy in the IMS Health Real World Data Adjudicated Claims US database from January 1, 2006, to June 30, 2015. Disease-modifying drug treatment was evaluated during the year prior to pregnancy (at three-month intervals), the three trimesters of pregnancy, puerperium (six weeks post-pregnancy), and one year post pregnancy (seven to 12 weeks post pregnancy and three to six, six to nine, and nine to 12 months post pregnancy). The researchers evaluated the proportion of women exposed to disease-modifying drug treatment during the 12 time periods. Results were also stratified by the number of relapses women experienced in the year prior to pregnancy.

Of 190,475 women with MS, 2,158 met eligibility criteria. Mean age was 30.26. Most women had commercial health insurance (98%) and were from the Midwest (32%), South (30%), or Northeast (29%) regions of the US.

The proportion of women with MS and a live birth treated with any disease-modifying drug was 20.48% at nine to 12 months pre-pregnancy, 21.46% at six to nine months pre-pregnancy, 20.62% at three to six months pre-pregnancy, and 17.75% at three months pre-pregnancy. During pregnancy, the proportion of women treated with a disease-modifying drug decreased to 12.05% during the first trimester and 1.90% during the second trimester, and then increased slightly to 2.97% during the third trimester. The proportion of women treated with disease-modifying drugs increased to 8.34% during puerperium, 12.93% during seven to 12 weeks post partum, 21.97% during three to six months post partum, 24.47% during six to nine months post partum, and 25.49% during nine to 12 months post partum. The majority of women (81.9%) had received disease-modifying drug treatment by six to nine months post partum. The proportion of women with disease-modifying drug treatment before and after pregnancy increased numerically with the number of relapses experienced before pregnancy.

Treatment After a Live Birth

In a separate analysis using the same cohort, Dr. Houtchens and colleagues looked closer at the time to initiation of disease-modifying drug treatment after a live birth in women with MS. Of the 2,094 women included in this analysis, the proportion with a live birth initiating a disease-modifying drug treatment within one year was 28.46%, and the proportion with no disease-modifying treatment within one year was 71.54%.

For those initiating a disease-modifying treatment within one year, mean time from live birth to first treatment was 118.98 days, and median time to first treatment was 93.50 days. A total of 16.11% received a disease-modifying drug less than 30 days after live birth, approximately half initiated a treatment within 90 days (47.82%), and three-quarters initiated a disease-modifying drug within six months (75.5%). The proportion of patients initiating treatment within one year after live birth increased with higher numbers of pre-pregnancy relapses (zero relapses, n = 441, 24.53%; one relapse, n = 108, 50.94%; two relapses, n = 33, 54.10%; three or more relapses, n = 14, 60.87%). The mean number of days until disease-modifying drug initiation for those receiving treatment within one year who had zero pre-pregnancy relapses was 123.57 (median, 99); one relapse, 107.95 (median, 80); two relapses, 120.76 (median, 98); and three or more relapses, 55.57 (median, 49.5). Patients who received disease-modifying drug treatment one year pre-pregnancy were more likely to receive treatment within one year after delivery, compared with patients without exposure to treatment in the year before pregnancy (72.58% vs 12.44%).

This study was supported by EMD Serono.

Treatment Before, During, and After Pregnancy

To evaluate treatment patterns before, during, and after pregnancy in women with MS and a live birth, Dr. Houtchens and colleagues used a US administrative claims database to conduct a retrospective analysis of women ages 18 to 65 with MS, a claim indicative of a live birth, and one-year continuous eligibility before and after pregnancy in the IMS Health Real World Data Adjudicated Claims US database from January 1, 2006, to June 30, 2015. Disease-modifying drug treatment was evaluated during the year prior to pregnancy (at three-month intervals), the three trimesters of pregnancy, puerperium (six weeks post-pregnancy), and one year post pregnancy (seven to 12 weeks post pregnancy and three to six, six to nine, and nine to 12 months post pregnancy). The researchers evaluated the proportion of women exposed to disease-modifying drug treatment during the 12 time periods. Results were also stratified by the number of relapses women experienced in the year prior to pregnancy.

Of 190,475 women with MS, 2,158 met eligibility criteria. Mean age was 30.26. Most women had commercial health insurance (98%) and were from the Midwest (32%), South (30%), or Northeast (29%) regions of the US.

The proportion of women with MS and a live birth treated with any disease-modifying drug was 20.48% at nine to 12 months pre-pregnancy, 21.46% at six to nine months pre-pregnancy, 20.62% at three to six months pre-pregnancy, and 17.75% at three months pre-pregnancy. During pregnancy, the proportion of women treated with a disease-modifying drug decreased to 12.05% during the first trimester and 1.90% during the second trimester, and then increased slightly to 2.97% during the third trimester. The proportion of women treated with disease-modifying drugs increased to 8.34% during puerperium, 12.93% during seven to 12 weeks post partum, 21.97% during three to six months post partum, 24.47% during six to nine months post partum, and 25.49% during nine to 12 months post partum. The majority of women (81.9%) had received disease-modifying drug treatment by six to nine months post partum. The proportion of women with disease-modifying drug treatment before and after pregnancy increased numerically with the number of relapses experienced before pregnancy.

Treatment After a Live Birth

In a separate analysis using the same cohort, Dr. Houtchens and colleagues looked closer at the time to initiation of disease-modifying drug treatment after a live birth in women with MS. Of the 2,094 women included in this analysis, the proportion with a live birth initiating a disease-modifying drug treatment within one year was 28.46%, and the proportion with no disease-modifying treatment within one year was 71.54%.

For those initiating a disease-modifying treatment within one year, mean time from live birth to first treatment was 118.98 days, and median time to first treatment was 93.50 days. A total of 16.11% received a disease-modifying drug less than 30 days after live birth, approximately half initiated a treatment within 90 days (47.82%), and three-quarters initiated a disease-modifying drug within six months (75.5%). The proportion of patients initiating treatment within one year after live birth increased with higher numbers of pre-pregnancy relapses (zero relapses, n = 441, 24.53%; one relapse, n = 108, 50.94%; two relapses, n = 33, 54.10%; three or more relapses, n = 14, 60.87%). The mean number of days until disease-modifying drug initiation for those receiving treatment within one year who had zero pre-pregnancy relapses was 123.57 (median, 99); one relapse, 107.95 (median, 80); two relapses, 120.76 (median, 98); and three or more relapses, 55.57 (median, 49.5). Patients who received disease-modifying drug treatment one year pre-pregnancy were more likely to receive treatment within one year after delivery, compared with patients without exposure to treatment in the year before pregnancy (72.58% vs 12.44%).

This study was supported by EMD Serono.

Treatment Before, During, and After Pregnancy

To evaluate treatment patterns before, during, and after pregnancy in women with MS and a live birth, Dr. Houtchens and colleagues used a US administrative claims database to conduct a retrospective analysis of women ages 18 to 65 with MS, a claim indicative of a live birth, and one-year continuous eligibility before and after pregnancy in the IMS Health Real World Data Adjudicated Claims US database from January 1, 2006, to June 30, 2015. Disease-modifying drug treatment was evaluated during the year prior to pregnancy (at three-month intervals), the three trimesters of pregnancy, puerperium (six weeks post-pregnancy), and one year post pregnancy (seven to 12 weeks post pregnancy and three to six, six to nine, and nine to 12 months post pregnancy). The researchers evaluated the proportion of women exposed to disease-modifying drug treatment during the 12 time periods. Results were also stratified by the number of relapses women experienced in the year prior to pregnancy.

Of 190,475 women with MS, 2,158 met eligibility criteria. Mean age was 30.26. Most women had commercial health insurance (98%) and were from the Midwest (32%), South (30%), or Northeast (29%) regions of the US.

The proportion of women with MS and a live birth treated with any disease-modifying drug was 20.48% at nine to 12 months pre-pregnancy, 21.46% at six to nine months pre-pregnancy, 20.62% at three to six months pre-pregnancy, and 17.75% at three months pre-pregnancy. During pregnancy, the proportion of women treated with a disease-modifying drug decreased to 12.05% during the first trimester and 1.90% during the second trimester, and then increased slightly to 2.97% during the third trimester. The proportion of women treated with disease-modifying drugs increased to 8.34% during puerperium, 12.93% during seven to 12 weeks post partum, 21.97% during three to six months post partum, 24.47% during six to nine months post partum, and 25.49% during nine to 12 months post partum. The majority of women (81.9%) had received disease-modifying drug treatment by six to nine months post partum. The proportion of women with disease-modifying drug treatment before and after pregnancy increased numerically with the number of relapses experienced before pregnancy.

Treatment After a Live Birth

In a separate analysis using the same cohort, Dr. Houtchens and colleagues looked closer at the time to initiation of disease-modifying drug treatment after a live birth in women with MS. Of the 2,094 women included in this analysis, the proportion with a live birth initiating a disease-modifying drug treatment within one year was 28.46%, and the proportion with no disease-modifying treatment within one year was 71.54%.

For those initiating a disease-modifying treatment within one year, mean time from live birth to first treatment was 118.98 days, and median time to first treatment was 93.50 days. A total of 16.11% received a disease-modifying drug less than 30 days after live birth, approximately half initiated a treatment within 90 days (47.82%), and three-quarters initiated a disease-modifying drug within six months (75.5%). The proportion of patients initiating treatment within one year after live birth increased with higher numbers of pre-pregnancy relapses (zero relapses, n = 441, 24.53%; one relapse, n = 108, 50.94%; two relapses, n = 33, 54.10%; three or more relapses, n = 14, 60.87%). The mean number of days until disease-modifying drug initiation for those receiving treatment within one year who had zero pre-pregnancy relapses was 123.57 (median, 99); one relapse, 107.95 (median, 80); two relapses, 120.76 (median, 98); and three or more relapses, 55.57 (median, 49.5). Patients who received disease-modifying drug treatment one year pre-pregnancy were more likely to receive treatment within one year after delivery, compared with patients without exposure to treatment in the year before pregnancy (72.58% vs 12.44%).

This study was supported by EMD Serono.

Photo from Penn Medicine

CHICAGO—Outcomes for pediatric patients with relapsed acute lymphoblastic leukemia (ALL) are dismal, with the probability of event-free survival ranging from 15% to 70% after a first relapse to 15% to 20% after a second relapse.

“So novel therapies are obviously urgently needed,” Mala Kiran Talekar, MD, of the Children's Hospital of Philadelphia in Pennsylvania, affirmed. “And herein comes the role of CAR T cells as a breakthrough therapy for relapsed/refractory pediatric ALL.”

She presented the outcome of chimeric antigen receptor (CAR) T-cell therapy in pediatric patients with non-CNS extramedullary (EM) relapse at the ASCO 2017 Annual meeting as abstract 10507.

The investigators had drawn the patient population for this analysis from 2 CAR studies, CTL019 and CTL119.

CTL019, which had already been completed, employed a murine CAR, and CTL119 is ongoing and uses a humanized CAR.

Of the 60 patients enrolled in CTL019, 56 (93%) achieved a complete response (CR) at day 28, and 100% had a CNS remission. Their 12-month overall survival (OS) was 79%.

“[K]eep in mind, when the study first started,” Dr Talekar said, “the patient population that had been referred to us was patients who had suffered a second or greater relapse or had been refractory to forms of treatment available to them, and the majority had been refractory to multiple therapies.”

The humanized CAR study, CTL119, is divided into 2 cohorts—one with CAR-naïve patients (n=22) and the other a CAR-retreatment arm (n=15) with patients who had received previous CAR therapy and relapsed.

Dr Talekar explained that the humanized CAR was made with the intention of decreasing rejection or loss of persistence of the T cells related to murine antigenicity.

Nine patients (60%) in the CAR-retreatment arm achieved a CR at day 28, and at 6 months, 78% experienced relapse-free survival (RFS) with a median follow-up of 12 months.

All of the CAR-naïve patients achieved CR at day 28, with 86% achieving RFS at 6 months, with a median follow-up of 10 months.

ALL with EM involvement

The investigators identified 10 pediatric patients treated in the murine (n=6) or humanized (n=4) trials who had received CAR therapy for isolated extramedullary disease or for combined bone marrow extramedullary (BM/EM) relapse of ALL.

They defined EM relapse as involvement of a non-CNS site confirmed by imaging with or without pathology within 12 months of CAR T-cell infusion. After infusion, patients had diagnostic imaging performed at 1, 3, 6, 9, and 12 months.

Of the 10 patients, 5 had active EM involvement at the time of infusion, 2 had isolated EM relapse—1 with parotid and multifocal bony lesions and 1 with testis and sinus lesions—and 5 had multiple sites of EM relapse.

The patients had 2 to 4 prior ALL relapses, 2 had prior local radiation to the EM site, and all 10 had received prior bone marrow transplants.

Three patients had an MLL rearrangement, 1 had hypodiploid ALL, and 1 had trisomy 21.

Nine of the 10 patients achieved MRD-negative CR at day 28.

One patient was not evaluable because his disease progressed within 2 weeks of CAR therapy in both the bone marrow and EM site. He died 6 weeks after the infusion.

Five patients evaluated by serial imaging had objective responses. Two had no evidence of EM disease by day 28, 2 had resolution by 3 months, and 1 had continued decrease in the size of her uterine mass at 3 and 6 months. She underwent hysterectomy at 8 months with no evidence of disease on pathology.

Four patients with a prior history of skin or testicular involvement had no evidence of disease by exam at day 28.

Three of the 9 patients relapsed with CD19+ disease. One had skin/medullary involvement and died at 38 months after CAR T-cell infusion. And 2 had medullary disease: 1 died at 17 months and 1 is alive at 28 months.

The remaining 6 patients are alive and well at a median follow-up of 10 months (range, 3 – 16 months) without recurrence of disease.

The investigators therefore concluded that single agent CAR T-cell immunotherapy can induce potent and durable response in patients with EM relapse of their ALL. 

Photo from Penn Medicine

CHICAGO—Outcomes for pediatric patients with relapsed acute lymphoblastic leukemia (ALL) are dismal, with the probability of event-free survival ranging from 15% to 70% after a first relapse to 15% to 20% after a second relapse.

“So novel therapies are obviously urgently needed,” Mala Kiran Talekar, MD, of the Children's Hospital of Philadelphia in Pennsylvania, affirmed. “And herein comes the role of CAR T cells as a breakthrough therapy for relapsed/refractory pediatric ALL.”

She presented the outcome of chimeric antigen receptor (CAR) T-cell therapy in pediatric patients with non-CNS extramedullary (EM) relapse at the ASCO 2017 Annual meeting as abstract 10507.

The investigators had drawn the patient population for this analysis from 2 CAR studies, CTL019 and CTL119.

CTL019, which had already been completed, employed a murine CAR, and CTL119 is ongoing and uses a humanized CAR.

Of the 60 patients enrolled in CTL019, 56 (93%) achieved a complete response (CR) at day 28, and 100% had a CNS remission. Their 12-month overall survival (OS) was 79%.

“[K]eep in mind, when the study first started,” Dr Talekar said, “the patient population that had been referred to us was patients who had suffered a second or greater relapse or had been refractory to forms of treatment available to them, and the majority had been refractory to multiple therapies.”

The humanized CAR study, CTL119, is divided into 2 cohorts—one with CAR-naïve patients (n=22) and the other a CAR-retreatment arm (n=15) with patients who had received previous CAR therapy and relapsed.

Dr Talekar explained that the humanized CAR was made with the intention of decreasing rejection or loss of persistence of the T cells related to murine antigenicity.

Nine patients (60%) in the CAR-retreatment arm achieved a CR at day 28, and at 6 months, 78% experienced relapse-free survival (RFS) with a median follow-up of 12 months.

All of the CAR-naïve patients achieved CR at day 28, with 86% achieving RFS at 6 months, with a median follow-up of 10 months.

ALL with EM involvement

The investigators identified 10 pediatric patients treated in the murine (n=6) or humanized (n=4) trials who had received CAR therapy for isolated extramedullary disease or for combined bone marrow extramedullary (BM/EM) relapse of ALL.

They defined EM relapse as involvement of a non-CNS site confirmed by imaging with or without pathology within 12 months of CAR T-cell infusion. After infusion, patients had diagnostic imaging performed at 1, 3, 6, 9, and 12 months.

Of the 10 patients, 5 had active EM involvement at the time of infusion, 2 had isolated EM relapse—1 with parotid and multifocal bony lesions and 1 with testis and sinus lesions—and 5 had multiple sites of EM relapse.

The patients had 2 to 4 prior ALL relapses, 2 had prior local radiation to the EM site, and all 10 had received prior bone marrow transplants.

Three patients had an MLL rearrangement, 1 had hypodiploid ALL, and 1 had trisomy 21.

Nine of the 10 patients achieved MRD-negative CR at day 28.

One patient was not evaluable because his disease progressed within 2 weeks of CAR therapy in both the bone marrow and EM site. He died 6 weeks after the infusion.

Five patients evaluated by serial imaging had objective responses. Two had no evidence of EM disease by day 28, 2 had resolution by 3 months, and 1 had continued decrease in the size of her uterine mass at 3 and 6 months. She underwent hysterectomy at 8 months with no evidence of disease on pathology.

Four patients with a prior history of skin or testicular involvement had no evidence of disease by exam at day 28.

Three of the 9 patients relapsed with CD19+ disease. One had skin/medullary involvement and died at 38 months after CAR T-cell infusion. And 2 had medullary disease: 1 died at 17 months and 1 is alive at 28 months.

The remaining 6 patients are alive and well at a median follow-up of 10 months (range, 3 – 16 months) without recurrence of disease.

The investigators therefore concluded that single agent CAR T-cell immunotherapy can induce potent and durable response in patients with EM relapse of their ALL. 

Photo from Penn Medicine

CHICAGO—Outcomes for pediatric patients with relapsed acute lymphoblastic leukemia (ALL) are dismal, with the probability of event-free survival ranging from 15% to 70% after a first relapse to 15% to 20% after a second relapse.

“So novel therapies are obviously urgently needed,” Mala Kiran Talekar, MD, of the Children's Hospital of Philadelphia in Pennsylvania, affirmed. “And herein comes the role of CAR T cells as a breakthrough therapy for relapsed/refractory pediatric ALL.”

She presented the outcome of chimeric antigen receptor (CAR) T-cell therapy in pediatric patients with non-CNS extramedullary (EM) relapse at the ASCO 2017 Annual meeting as abstract 10507.

The investigators had drawn the patient population for this analysis from 2 CAR studies, CTL019 and CTL119.

CTL019, which had already been completed, employed a murine CAR, and CTL119 is ongoing and uses a humanized CAR.

Of the 60 patients enrolled in CTL019, 56 (93%) achieved a complete response (CR) at day 28, and 100% had a CNS remission. Their 12-month overall survival (OS) was 79%.

“[K]eep in mind, when the study first started,” Dr Talekar said, “the patient population that had been referred to us was patients who had suffered a second or greater relapse or had been refractory to forms of treatment available to them, and the majority had been refractory to multiple therapies.”

The humanized CAR study, CTL119, is divided into 2 cohorts—one with CAR-naïve patients (n=22) and the other a CAR-retreatment arm (n=15) with patients who had received previous CAR therapy and relapsed.

Dr Talekar explained that the humanized CAR was made with the intention of decreasing rejection or loss of persistence of the T cells related to murine antigenicity.

Nine patients (60%) in the CAR-retreatment arm achieved a CR at day 28, and at 6 months, 78% experienced relapse-free survival (RFS) with a median follow-up of 12 months.

All of the CAR-naïve patients achieved CR at day 28, with 86% achieving RFS at 6 months, with a median follow-up of 10 months.

ALL with EM involvement

The investigators identified 10 pediatric patients treated in the murine (n=6) or humanized (n=4) trials who had received CAR therapy for isolated extramedullary disease or for combined bone marrow extramedullary (BM/EM) relapse of ALL.

They defined EM relapse as involvement of a non-CNS site confirmed by imaging with or without pathology within 12 months of CAR T-cell infusion. After infusion, patients had diagnostic imaging performed at 1, 3, 6, 9, and 12 months.

Of the 10 patients, 5 had active EM involvement at the time of infusion, 2 had isolated EM relapse—1 with parotid and multifocal bony lesions and 1 with testis and sinus lesions—and 5 had multiple sites of EM relapse.

The patients had 2 to 4 prior ALL relapses, 2 had prior local radiation to the EM site, and all 10 had received prior bone marrow transplants.

Three patients had an MLL rearrangement, 1 had hypodiploid ALL, and 1 had trisomy 21.

Nine of the 10 patients achieved MRD-negative CR at day 28.

One patient was not evaluable because his disease progressed within 2 weeks of CAR therapy in both the bone marrow and EM site. He died 6 weeks after the infusion.

Five patients evaluated by serial imaging had objective responses. Two had no evidence of EM disease by day 28, 2 had resolution by 3 months, and 1 had continued decrease in the size of her uterine mass at 3 and 6 months. She underwent hysterectomy at 8 months with no evidence of disease on pathology.

Four patients with a prior history of skin or testicular involvement had no evidence of disease by exam at day 28.

Three of the 9 patients relapsed with CD19+ disease. One had skin/medullary involvement and died at 38 months after CAR T-cell infusion. And 2 had medullary disease: 1 died at 17 months and 1 is alive at 28 months.

The remaining 6 patients are alive and well at a median follow-up of 10 months (range, 3 – 16 months) without recurrence of disease.

The investigators therefore concluded that single agent CAR T-cell immunotherapy can induce potent and durable response in patients with EM relapse of their ALL.