Case Reports

THE CASE

A healthy 6-month-old girl born via spontaneous vaginal delivery to a 33-year-old mother presented to her family physician (FP) for a routine well-child examination. The mother’s prenatal anatomy scan, delivery, and personal and family history were unremarkable. The patient was not firstborn or breech, and there was no family history of hip dysplasia. On prior infant well-child examinations, Ortolani and Barlow maneuvers were negative, and the patient demonstrated spontaneous movement of both legs. There was no evidence of hip dysplasia, lower extremity weakness, musculoskeletal abnormalities, or abnormal skin markings. The patient had normal growth and development (50th percentile for height and weight, average Ages & Stages Questionnaire scores) and no history of infection or trauma.

At the current presentation, the FP noted a leg-length discrepancy while palpating the bony (patellar and malleolar) landmarks of the lower extremities, but the right and left anterior superior iliac spine was symmetrical. The gluteal folds and popliteal fossae were asymmetric, a Galeazzi test was positive, and the right leg measured approximately 2 cm shorter than the left leg. There was no evidence of scoliosis or pelvic abnormalities. Physical examination revealed no ecchymosis or trauma. Orthopedic evaluation by the FP of the hips, knees, and ankles was normal, including negative repeat Ortolani and Barlow maneuvers and normal range of motion. We obtained x-rays of the lower extremities and ordered an orthopedic consultation.

THE DIAGNOSIS

The differential diagnosis included congenital, traumatic, infectious, inflammatory, idiopathic, and neurologic causes.^1-3 The most common etiologies of leg-length discrepancies are summarized in TABLE 1.^1-3 Radiographic imaging showed a femur length discrepancy, which was determined to be congenital without indication of trauma or disease; therefore, a diagnosis of congenital femoral bowing was made.

Initial orthopedic evaluation revealed a femur length discrepancy of approximately 2 cm. Plain films showed lateral femoral bowing (FIGURE 1A). Regular interval imaging performed at routine well-child examinations at 19 months, 3 years, and 5 years of age showed progression of the femoral length discrepancy from 2 cm to nearly 5 cm, remaining proportionally constant, as well as increasing genu valgum of the right leg up to 12 degrees (FIGURE 1B-D).

DISCUSSION

Congenital femoral bowing, which can present as a leg-length discrepancy in infants, is a relatively rare finding with an incidence of 1 per 52,000 births.⁴ Our patient presented with an isolated limb deformity, but congenital femoral bowing is recognized as a clinical feature of several skeletal dysplasias (TABLE 2).⁵

What’s recommended

The American Academy of Pediatrics recommends routine age-appropriate physical examination without specifying leg-length assessment.⁶ There is insufficient evidence, according to the US Preventive Services Task Force and the American Academy of Pediatrics, regarding the value of routine infant hip and leg-length assessment for developmental dysplasia of the hip and other musculoskeletal abnormalities; however, both agree that abnormal findings require follow-up and management.^6-8

Congenital femoral bowing requires plain film diagnosis

Following physical examination, diagnosis of congenital femoral bowing should be confirmed by plain films. Plain radiography remains the main imaging modality for proximal focal femoral deficiency and fibular hemimelia, and appropriate identification of the osseous abnormalities seen on radiographs allows for accurate classification of congenital femoral bowing, prognosis, and surgical planning. (Minor malformations associated with congenital leg-length discrepancies are not typically identified as being part of a larger syndromic diagnosis.⁴) The patient should subsequently be referred to an orthopedist for monitoring and to establish a long-term management plan.

Continue to: Early diagnosis can improve treatment outcome

Early diagnosis can improve treatment outcome

Both early diagnosis of congenital femoral bowing and prediction of leg-length discrepancy at skeletal maturity can influence potential treatment options, which range from conservative management (eg, watchful waiting, physical therapy, shoe lifts, orthotics, bracing) to surgical intervention. Several models have been used to predict skeletal growth, including the Moseley straight line graph, Green and Anderson growth curve, Amstutz method, and Paley’s multiplier method.^4,9-14

Congenital femoral bowing may present clinically as a leg-length discrepancy with no indication of trauma or disease.

Intervention for leg-length discrepancy generally is dictated by the magnitude of the inequality and the presence of functional deficits and/or pain.² If the degree of femur angulation begins to affect structural development, surgical intervention should be considered to align development and/or correct the discrepancy. Physical therapy, shoe lifts, orthotics, and bracing are treatment options for managing smaller discrepancies.^2,15

Our patient. The physician (CP) reviewed treatment options with the family that included watchful waiting, use of a shoe lift and/or orthotics, and bracing. The family chose watchful waiting due to the structural integrity of the patient’s other major joints and her relatively preserved function. The patient demonstrated mild gross motor delay at routine well-child visits at 9, 12, and 15 months, but was walking by 19 months. Her development was otherwise normal as documented via regular developmental screenings at routine well-child examinations. The patient participated in home physical therapy to maintain strength, flexibility, and functional mobility, and she was able to ambulate by walking on her right toes.

Surgery. Ultimately the patient underwent medial distal femoral hemiepiphysiodesis of the right lower extremity at 6 years of age due to increasing leg-length discrepancy and lateralization of the patella from the valgus deformity. The patient’s mother reported that she did well postoperatively, with increased range of motion, improved physical capabilities, and reduced discomfort in the right leg. She continued to participate in physical therapy and had routine follow-up with her physical therapist, her FP, and orthopedist.

A second surgery. At approximately 8 years and 9 months of age, the orthopedist noted that the patient’s leg-length discrepancy had increased, and she had right extensor mechanism malalignment and severe patellar subluxation. The patient subsequently underwent surgery to remove the existing hardware, including right extensor mechanism realignment via a Roux-Goldthwait procedure (with reconstruction of the medial patellofemoral ligament and anterior cruciate ligament), as well as left distal femoral epiphysiodesis. She did very well postoperatively and continues to participate in physical therapy approximately once weekly. She has had an improvement in her gait and stability using shoe lifts.

Continue to: THE TAKEAWAY

A routine well-child examination can be an opportunity to identify congenital musculoskeletal problems. Congenital femoral bowing is a relatively rare finding⁴ that may present as a leg-length discrepancy. With proper evaluation, including visual inspection, palpation, range-of-motion testing, and special tests as needed (eg, Galeazzi test, Ortolani and Barlow maneuvers), early intervention is possible if a leg-length discrepancy is noted. Close monitoring of gait abnormalities at routine well-child visits is essential.

Physical therapy, shoe lift therapy, and surgical approaches are treatment options for leg-length discrepancy,² and early intervention can improve treatment outcomes.¹⁴ Understanding how to manage congenital femoral bowing over time is important in providing options and counselling patients and their families.¹⁵

Treatment of leg-length discrepancy in pediatric patients requires long-term management with a team approach that includes patients and their families. The goal of intervention is to reduce physical and emotional trauma, while addressing complications and maintaining function of the affected limb, as well as the whole body.¹⁵

CORRESPONDENCE
Beth P. Davis, DPT, MBA, FNAP, Emory University School of Medicine, Department of Rehabilitation Medicine, Division of Physical Therapy, 1462 Clifton Road NE, Suite 312, Atlanta, GA 30342; [email protected].

THE CASE

A healthy 6-month-old girl born via spontaneous vaginal delivery to a 33-year-old mother presented to her family physician (FP) for a routine well-child examination. The mother’s prenatal anatomy scan, delivery, and personal and family history were unremarkable. The patient was not firstborn or breech, and there was no family history of hip dysplasia. On prior infant well-child examinations, Ortolani and Barlow maneuvers were negative, and the patient demonstrated spontaneous movement of both legs. There was no evidence of hip dysplasia, lower extremity weakness, musculoskeletal abnormalities, or abnormal skin markings. The patient had normal growth and development (50th percentile for height and weight, average Ages & Stages Questionnaire scores) and no history of infection or trauma.

At the current presentation, the FP noted a leg-length discrepancy while palpating the bony (patellar and malleolar) landmarks of the lower extremities, but the right and left anterior superior iliac spine was symmetrical. The gluteal folds and popliteal fossae were asymmetric, a Galeazzi test was positive, and the right leg measured approximately 2 cm shorter than the left leg. There was no evidence of scoliosis or pelvic abnormalities. Physical examination revealed no ecchymosis or trauma. Orthopedic evaluation by the FP of the hips, knees, and ankles was normal, including negative repeat Ortolani and Barlow maneuvers and normal range of motion. We obtained x-rays of the lower extremities and ordered an orthopedic consultation.

THE DIAGNOSIS

The differential diagnosis included congenital, traumatic, infectious, inflammatory, idiopathic, and neurologic causes.^1-3 The most common etiologies of leg-length discrepancies are summarized in TABLE 1.^1-3 Radiographic imaging showed a femur length discrepancy, which was determined to be congenital without indication of trauma or disease; therefore, a diagnosis of congenital femoral bowing was made.

Initial orthopedic evaluation revealed a femur length discrepancy of approximately 2 cm. Plain films showed lateral femoral bowing (FIGURE 1A). Regular interval imaging performed at routine well-child examinations at 19 months, 3 years, and 5 years of age showed progression of the femoral length discrepancy from 2 cm to nearly 5 cm, remaining proportionally constant, as well as increasing genu valgum of the right leg up to 12 degrees (FIGURE 1B-D).

DISCUSSION

Congenital femoral bowing, which can present as a leg-length discrepancy in infants, is a relatively rare finding with an incidence of 1 per 52,000 births.⁴ Our patient presented with an isolated limb deformity, but congenital femoral bowing is recognized as a clinical feature of several skeletal dysplasias (TABLE 2).⁵

What’s recommended

The American Academy of Pediatrics recommends routine age-appropriate physical examination without specifying leg-length assessment.⁶ There is insufficient evidence, according to the US Preventive Services Task Force and the American Academy of Pediatrics, regarding the value of routine infant hip and leg-length assessment for developmental dysplasia of the hip and other musculoskeletal abnormalities; however, both agree that abnormal findings require follow-up and management.^6-8

Congenital femoral bowing requires plain film diagnosis

Following physical examination, diagnosis of congenital femoral bowing should be confirmed by plain films. Plain radiography remains the main imaging modality for proximal focal femoral deficiency and fibular hemimelia, and appropriate identification of the osseous abnormalities seen on radiographs allows for accurate classification of congenital femoral bowing, prognosis, and surgical planning. (Minor malformations associated with congenital leg-length discrepancies are not typically identified as being part of a larger syndromic diagnosis.⁴) The patient should subsequently be referred to an orthopedist for monitoring and to establish a long-term management plan.

Continue to: Early diagnosis can improve treatment outcome

Early diagnosis can improve treatment outcome

Both early diagnosis of congenital femoral bowing and prediction of leg-length discrepancy at skeletal maturity can influence potential treatment options, which range from conservative management (eg, watchful waiting, physical therapy, shoe lifts, orthotics, bracing) to surgical intervention. Several models have been used to predict skeletal growth, including the Moseley straight line graph, Green and Anderson growth curve, Amstutz method, and Paley’s multiplier method.^4,9-14

Congenital femoral bowing may present clinically as a leg-length discrepancy with no indication of trauma or disease.

Intervention for leg-length discrepancy generally is dictated by the magnitude of the inequality and the presence of functional deficits and/or pain.² If the degree of femur angulation begins to affect structural development, surgical intervention should be considered to align development and/or correct the discrepancy. Physical therapy, shoe lifts, orthotics, and bracing are treatment options for managing smaller discrepancies.^2,15

Our patient. The physician (CP) reviewed treatment options with the family that included watchful waiting, use of a shoe lift and/or orthotics, and bracing. The family chose watchful waiting due to the structural integrity of the patient’s other major joints and her relatively preserved function. The patient demonstrated mild gross motor delay at routine well-child visits at 9, 12, and 15 months, but was walking by 19 months. Her development was otherwise normal as documented via regular developmental screenings at routine well-child examinations. The patient participated in home physical therapy to maintain strength, flexibility, and functional mobility, and she was able to ambulate by walking on her right toes.

Surgery. Ultimately the patient underwent medial distal femoral hemiepiphysiodesis of the right lower extremity at 6 years of age due to increasing leg-length discrepancy and lateralization of the patella from the valgus deformity. The patient’s mother reported that she did well postoperatively, with increased range of motion, improved physical capabilities, and reduced discomfort in the right leg. She continued to participate in physical therapy and had routine follow-up with her physical therapist, her FP, and orthopedist.

A second surgery. At approximately 8 years and 9 months of age, the orthopedist noted that the patient’s leg-length discrepancy had increased, and she had right extensor mechanism malalignment and severe patellar subluxation. The patient subsequently underwent surgery to remove the existing hardware, including right extensor mechanism realignment via a Roux-Goldthwait procedure (with reconstruction of the medial patellofemoral ligament and anterior cruciate ligament), as well as left distal femoral epiphysiodesis. She did very well postoperatively and continues to participate in physical therapy approximately once weekly. She has had an improvement in her gait and stability using shoe lifts.

Continue to: THE TAKEAWAY

A routine well-child examination can be an opportunity to identify congenital musculoskeletal problems. Congenital femoral bowing is a relatively rare finding⁴ that may present as a leg-length discrepancy. With proper evaluation, including visual inspection, palpation, range-of-motion testing, and special tests as needed (eg, Galeazzi test, Ortolani and Barlow maneuvers), early intervention is possible if a leg-length discrepancy is noted. Close monitoring of gait abnormalities at routine well-child visits is essential.

Physical therapy, shoe lift therapy, and surgical approaches are treatment options for leg-length discrepancy,² and early intervention can improve treatment outcomes.¹⁴ Understanding how to manage congenital femoral bowing over time is important in providing options and counselling patients and their families.¹⁵

Treatment of leg-length discrepancy in pediatric patients requires long-term management with a team approach that includes patients and their families. The goal of intervention is to reduce physical and emotional trauma, while addressing complications and maintaining function of the affected limb, as well as the whole body.¹⁵

CORRESPONDENCE
Beth P. Davis, DPT, MBA, FNAP, Emory University School of Medicine, Department of Rehabilitation Medicine, Division of Physical Therapy, 1462 Clifton Road NE, Suite 312, Atlanta, GA 30342; [email protected].

THE CASE

A healthy 6-month-old girl born via spontaneous vaginal delivery to a 33-year-old mother presented to her family physician (FP) for a routine well-child examination. The mother’s prenatal anatomy scan, delivery, and personal and family history were unremarkable. The patient was not firstborn or breech, and there was no family history of hip dysplasia. On prior infant well-child examinations, Ortolani and Barlow maneuvers were negative, and the patient demonstrated spontaneous movement of both legs. There was no evidence of hip dysplasia, lower extremity weakness, musculoskeletal abnormalities, or abnormal skin markings. The patient had normal growth and development (50th percentile for height and weight, average Ages & Stages Questionnaire scores) and no history of infection or trauma.

At the current presentation, the FP noted a leg-length discrepancy while palpating the bony (patellar and malleolar) landmarks of the lower extremities, but the right and left anterior superior iliac spine was symmetrical. The gluteal folds and popliteal fossae were asymmetric, a Galeazzi test was positive, and the right leg measured approximately 2 cm shorter than the left leg. There was no evidence of scoliosis or pelvic abnormalities. Physical examination revealed no ecchymosis or trauma. Orthopedic evaluation by the FP of the hips, knees, and ankles was normal, including negative repeat Ortolani and Barlow maneuvers and normal range of motion. We obtained x-rays of the lower extremities and ordered an orthopedic consultation.

THE DIAGNOSIS

The differential diagnosis included congenital, traumatic, infectious, inflammatory, idiopathic, and neurologic causes.^1-3 The most common etiologies of leg-length discrepancies are summarized in TABLE 1.^1-3 Radiographic imaging showed a femur length discrepancy, which was determined to be congenital without indication of trauma or disease; therefore, a diagnosis of congenital femoral bowing was made.

Initial orthopedic evaluation revealed a femur length discrepancy of approximately 2 cm. Plain films showed lateral femoral bowing (FIGURE 1A). Regular interval imaging performed at routine well-child examinations at 19 months, 3 years, and 5 years of age showed progression of the femoral length discrepancy from 2 cm to nearly 5 cm, remaining proportionally constant, as well as increasing genu valgum of the right leg up to 12 degrees (FIGURE 1B-D).

DISCUSSION

Congenital femoral bowing, which can present as a leg-length discrepancy in infants, is a relatively rare finding with an incidence of 1 per 52,000 births.⁴ Our patient presented with an isolated limb deformity, but congenital femoral bowing is recognized as a clinical feature of several skeletal dysplasias (TABLE 2).⁵

What’s recommended

The American Academy of Pediatrics recommends routine age-appropriate physical examination without specifying leg-length assessment.⁶ There is insufficient evidence, according to the US Preventive Services Task Force and the American Academy of Pediatrics, regarding the value of routine infant hip and leg-length assessment for developmental dysplasia of the hip and other musculoskeletal abnormalities; however, both agree that abnormal findings require follow-up and management.^6-8

Congenital femoral bowing requires plain film diagnosis

Following physical examination, diagnosis of congenital femoral bowing should be confirmed by plain films. Plain radiography remains the main imaging modality for proximal focal femoral deficiency and fibular hemimelia, and appropriate identification of the osseous abnormalities seen on radiographs allows for accurate classification of congenital femoral bowing, prognosis, and surgical planning. (Minor malformations associated with congenital leg-length discrepancies are not typically identified as being part of a larger syndromic diagnosis.⁴) The patient should subsequently be referred to an orthopedist for monitoring and to establish a long-term management plan.

Continue to: Early diagnosis can improve treatment outcome

Early diagnosis can improve treatment outcome

Both early diagnosis of congenital femoral bowing and prediction of leg-length discrepancy at skeletal maturity can influence potential treatment options, which range from conservative management (eg, watchful waiting, physical therapy, shoe lifts, orthotics, bracing) to surgical intervention. Several models have been used to predict skeletal growth, including the Moseley straight line graph, Green and Anderson growth curve, Amstutz method, and Paley’s multiplier method.^4,9-14

Congenital femoral bowing may present clinically as a leg-length discrepancy with no indication of trauma or disease.

Intervention for leg-length discrepancy generally is dictated by the magnitude of the inequality and the presence of functional deficits and/or pain.² If the degree of femur angulation begins to affect structural development, surgical intervention should be considered to align development and/or correct the discrepancy. Physical therapy, shoe lifts, orthotics, and bracing are treatment options for managing smaller discrepancies.^2,15

Our patient. The physician (CP) reviewed treatment options with the family that included watchful waiting, use of a shoe lift and/or orthotics, and bracing. The family chose watchful waiting due to the structural integrity of the patient’s other major joints and her relatively preserved function. The patient demonstrated mild gross motor delay at routine well-child visits at 9, 12, and 15 months, but was walking by 19 months. Her development was otherwise normal as documented via regular developmental screenings at routine well-child examinations. The patient participated in home physical therapy to maintain strength, flexibility, and functional mobility, and she was able to ambulate by walking on her right toes.

Surgery. Ultimately the patient underwent medial distal femoral hemiepiphysiodesis of the right lower extremity at 6 years of age due to increasing leg-length discrepancy and lateralization of the patella from the valgus deformity. The patient’s mother reported that she did well postoperatively, with increased range of motion, improved physical capabilities, and reduced discomfort in the right leg. She continued to participate in physical therapy and had routine follow-up with her physical therapist, her FP, and orthopedist.

A second surgery. At approximately 8 years and 9 months of age, the orthopedist noted that the patient’s leg-length discrepancy had increased, and she had right extensor mechanism malalignment and severe patellar subluxation. The patient subsequently underwent surgery to remove the existing hardware, including right extensor mechanism realignment via a Roux-Goldthwait procedure (with reconstruction of the medial patellofemoral ligament and anterior cruciate ligament), as well as left distal femoral epiphysiodesis. She did very well postoperatively and continues to participate in physical therapy approximately once weekly. She has had an improvement in her gait and stability using shoe lifts.

Continue to: THE TAKEAWAY

A routine well-child examination can be an opportunity to identify congenital musculoskeletal problems. Congenital femoral bowing is a relatively rare finding⁴ that may present as a leg-length discrepancy. With proper evaluation, including visual inspection, palpation, range-of-motion testing, and special tests as needed (eg, Galeazzi test, Ortolani and Barlow maneuvers), early intervention is possible if a leg-length discrepancy is noted. Close monitoring of gait abnormalities at routine well-child visits is essential.

Physical therapy, shoe lift therapy, and surgical approaches are treatment options for leg-length discrepancy,² and early intervention can improve treatment outcomes.¹⁴ Understanding how to manage congenital femoral bowing over time is important in providing options and counselling patients and their families.¹⁵

Treatment of leg-length discrepancy in pediatric patients requires long-term management with a team approach that includes patients and their families. The goal of intervention is to reduce physical and emotional trauma, while addressing complications and maintaining function of the affected limb, as well as the whole body.¹⁵

CORRESPONDENCE
Beth P. Davis, DPT, MBA, FNAP, Emory University School of Medicine, Department of Rehabilitation Medicine, Division of Physical Therapy, 1462 Clifton Road NE, Suite 312, Atlanta, GA 30342; [email protected].

THE CASE

A 61-year-old Caucasian woman presented with acute right shoulder pain that began after she received an influenza vaccination at a local pharmacy 2 weeks earlier. She pointed to the proximal-most aspect of her lateral right upper arm as the vaccination site. Her pain intensified with shoulder abduction, forward flexion, and reaching movements. She denied recent and past injury to her shoulder, fever, chills, rash, or skin changes at the injection site. She said her left shoulder did not bother her.

The patient had continued to participate in her aerobics class, despite the discomfort. Her medical history included hypertension and myocardial infarction, and the medications she was taking included lisinopril 20 mg/d, atenolol 50 mg/d, and aspirin 81 mg/d.

The physical exam revealed a thin female with no visible rashes or erythema on her right shoulder. While there was no deltoid atrophy in comparison to her unaffected shoulder, she generally had low muscle mass in both arms. A painful arc of abduction was present, as was pain with palpation of the supraspinatus insertion. No pain was appreciated over the short or long head of the biceps tendon or the sternoclavicular or acromioclavicular joints. Strength was 5/5 for all movements of the rotator cuff, but pain was reproduced with resisted shoulder abduction. A Hawkin’s test was positive, while Speed’s, Yergason’s, cross-arm abduction, and O’Brien’s tests were all negative.

THE DIAGNOSIS

Anteroposterior, Grashey, Y-view, and axillary view radiographs of the right shoulder were normal without any calcific tendinopathy, degenerative changes, or acute fractures. The patient’s history and physical exam were consistent with a rotator cuff tendinitis secondary to an immune response to an influenza vaccination that infiltrated the supraspinatus tendon.

DISCUSSION

Soreness, redness and swelling at the injection site, fever, body aches, and headache are common adverse effects of the influenza vaccine.¹Although rare, acute brachial neuritis, infection, rotator cuff injuries, and contusions of the humeral head have also been reported. ^2-5 Collectively, these conditions are referred to as shoulder injuries related to vaccination administration (SIRVA). There have been multiple SIRVA cases reported in the United States, and the US Court of Federal Claims has compensated >100 patients for SIRVA since 2011.⁶ There is currently no listing of SIRVA as a potential adverse reaction to the influenza vaccine on the package inserts or on the Centers for Disease Control and Prevention (CDC) Web site.

Shoulder soreness lasting <72 hours without functional impairment is likely due to soreness at the injection site. If symptoms do not resolve within 72 to 96 hours, consider a more thorough workup, with SIRVA being a possible diagnosis.^1,7 The etiology of SIRVA remains uncertain, but an inflammatory reaction from a vaccine mistakenly administered into the subacromial/subdeltoid bursa has been suggested. Whether this reaction is dependent on the nonantigenic or antigenic components of the vaccine has yet to be determined.

Symptoms of SIRVA include pain with arm movement, pain that is worse at night or awakens the patient from sleep, restricted range of motion, or arm weakness. Examination will reveal pain when resisting rotator cuff movements, particularly shoulder abduction. Advanced imaging can be considered when the diagnosis is in question. In previous cases of vaccine-associated rotator cuff tendinopathy in the authors’ practice, T2 magnetic resonance imaging (MRI) has shown focal inflammatory signal within the supraspinatus tendon and subacromial bursa.

Continue to: With support from the CDC...

With support from the CDC, the Immunization Action Coalition (IAC), a source of immunization information for health care professionals, recommends that vaccines be administered into the deltoid or vastus lateralis for individuals between the ages of 3 and 18 years and recommends the deltoid as the preferred location in adults ≥19 years. The IAC suggests increasing the needle length for intramuscular (IM) immunizations (depending on the weight of the patient), although in the authors’ experience, the adjustment of needle length may often be overlooked (TABLE⁷).

The majority of reported SIRVA cases caused by overpenetration have occurred in individuals weighing <140 lb or those who had little deltoid muscle bulk. An MRI study to evaluate optimal intramuscular needle length in pediatric patients found that the IAC-recommended needle lengths still allowed penetration of the subdeltoid space in a substantial number of patients.⁸ Classic teaching of IM deltoid injection landmarks is 3 fingerbreadths distal to the acromion, and a more proximal administration of a vaccine would allow penetration of the rotator cuff structures below.

How to manage the patient

Patients who develop SIRVA should be managed similarly to patients with tendinopathy from other causes. Treatment options include: physical therapy, anti-inflammatory medications, and subacromial corticosteroid injections. Given the significant discomfort and nighttime pain associated with rotator cuff tendinopathy, corticosteroid injections can offer rapid relief.

Limited data exist on the effect of corticosteroids on the suppression of the immune response in immunocompetent patients. Vaccinations are generally thought to stimulate an adequate immune response 14 days following administration, so our suggestion would be to re-vaccinate patients if a corticosteroid injection to treat SIRVA is completed prior to this.⁹

Our patient’s outcome

We talked to the patient about treatment options, which included physical therapy and nonsteroidal anti-inflammatory drugs (NSAIDs), but the patient elected to go forward with a corticosteroid injection. We administered 2 cc of Depo-Medrol 40 mg/mL with 2 cc of 1% lidocaine without epinephrine and 2 cc of 0.5% ropivacaine into her right shoulder subacromial space using a posterior approach. The patient noticed a 70% improvement in her pain immediately following the injection.

Continue to: Considering her influenza vaccine...

Considering her influenza vaccine was administered more than 14 days prior to her corticosteroid injection, we felt that she had mounted enough of an immune response for the vaccination to have been adequate for protection.⁹ Therefore, we told her that she didn’t need to be revaccinated for influenza this season. The case was reported to the Vaccine Adverse Event Reporting System (VAERS).

In previous cases of vaccine-associated rotator cuff tendonopathy, T2 MRI images have shown focal inflammatory signal within the supraspinatous tendon and subacromial bursa.

At the patient’s 2-month follow up, she reported an overall 80% improvement in pain. She continued to have occasional discomfort with certain movements, although the pain was relieved with over-the-counter anti-inflammatory medication. On physical exam she had an intact arc of abduction of the right shoulder to 150° without pain. Forward flexion and external and internal rotation were normal and pain free. She had mild pain with resisted abduction and a positive Hawkin’s test. The patient agreed to go to physical therapy to work on rotator cuff strengthening. She denied any known influenza infection up to that time.

THE TAKEAWAY

It’s important to consider rotator cuff injuries or SIRVA as a potential adverse effect of influenza vaccination administration. Thin patients and those with low deltoid muscle mass are at risk of vaccine over-penetration, and proximally placed deltoid vaccines may reach the rotator cuff structures below. Staff should be trained on appropriate techniques for administering influenza vaccinations to avoid causing SIRVA. Specifically:

• Intramuscular vaccines injected into the deltoid muscle should be 3 fingerbreadths distal to the acromion. A more proximal approach could potentially contact the rotator cuff muscles.
• Vaccine administration should mirror the position of the patient (eg, if the patient is sitting, the administrator should be sitting; if the patient is standing, the administrator should be standing).
• Needle length for vaccine administration should be adjusted according to the patient’s weight (TABLE⁷).

Following vaccination, it is important to keep 2 other points in mind. First, if a subacromial corticosteroid injection is used for treatment of SIRVA within the first 2 weeks of vaccine administration, consider revaccination. Second, be sure to use the VAERS to report any clinically significant medical event that occurs after vaccination. VAERS is a national vaccine safety surveillance program that is supported by the CDC and the US Food and Drug Administration. The VAERS reporting system can be accessed through www.vaers.hhhs.gov.

CORRESPONDENCE
Dusty Marie Narducci, MD, 5290 Big Island Drive, Unit 1303, Jacksonville, FL 32246; [email protected]

THE CASE

A 61-year-old Caucasian woman presented with acute right shoulder pain that began after she received an influenza vaccination at a local pharmacy 2 weeks earlier. She pointed to the proximal-most aspect of her lateral right upper arm as the vaccination site. Her pain intensified with shoulder abduction, forward flexion, and reaching movements. She denied recent and past injury to her shoulder, fever, chills, rash, or skin changes at the injection site. She said her left shoulder did not bother her.

The patient had continued to participate in her aerobics class, despite the discomfort. Her medical history included hypertension and myocardial infarction, and the medications she was taking included lisinopril 20 mg/d, atenolol 50 mg/d, and aspirin 81 mg/d.

The physical exam revealed a thin female with no visible rashes or erythema on her right shoulder. While there was no deltoid atrophy in comparison to her unaffected shoulder, she generally had low muscle mass in both arms. A painful arc of abduction was present, as was pain with palpation of the supraspinatus insertion. No pain was appreciated over the short or long head of the biceps tendon or the sternoclavicular or acromioclavicular joints. Strength was 5/5 for all movements of the rotator cuff, but pain was reproduced with resisted shoulder abduction. A Hawkin’s test was positive, while Speed’s, Yergason’s, cross-arm abduction, and O’Brien’s tests were all negative.

THE DIAGNOSIS

Anteroposterior, Grashey, Y-view, and axillary view radiographs of the right shoulder were normal without any calcific tendinopathy, degenerative changes, or acute fractures. The patient’s history and physical exam were consistent with a rotator cuff tendinitis secondary to an immune response to an influenza vaccination that infiltrated the supraspinatus tendon.

DISCUSSION

Soreness, redness and swelling at the injection site, fever, body aches, and headache are common adverse effects of the influenza vaccine.¹Although rare, acute brachial neuritis, infection, rotator cuff injuries, and contusions of the humeral head have also been reported. ^2-5 Collectively, these conditions are referred to as shoulder injuries related to vaccination administration (SIRVA). There have been multiple SIRVA cases reported in the United States, and the US Court of Federal Claims has compensated >100 patients for SIRVA since 2011.⁶ There is currently no listing of SIRVA as a potential adverse reaction to the influenza vaccine on the package inserts or on the Centers for Disease Control and Prevention (CDC) Web site.

Shoulder soreness lasting <72 hours without functional impairment is likely due to soreness at the injection site. If symptoms do not resolve within 72 to 96 hours, consider a more thorough workup, with SIRVA being a possible diagnosis.^1,7 The etiology of SIRVA remains uncertain, but an inflammatory reaction from a vaccine mistakenly administered into the subacromial/subdeltoid bursa has been suggested. Whether this reaction is dependent on the nonantigenic or antigenic components of the vaccine has yet to be determined.

Symptoms of SIRVA include pain with arm movement, pain that is worse at night or awakens the patient from sleep, restricted range of motion, or arm weakness. Examination will reveal pain when resisting rotator cuff movements, particularly shoulder abduction. Advanced imaging can be considered when the diagnosis is in question. In previous cases of vaccine-associated rotator cuff tendinopathy in the authors’ practice, T2 magnetic resonance imaging (MRI) has shown focal inflammatory signal within the supraspinatus tendon and subacromial bursa.

Continue to: With support from the CDC...

With support from the CDC, the Immunization Action Coalition (IAC), a source of immunization information for health care professionals, recommends that vaccines be administered into the deltoid or vastus lateralis for individuals between the ages of 3 and 18 years and recommends the deltoid as the preferred location in adults ≥19 years. The IAC suggests increasing the needle length for intramuscular (IM) immunizations (depending on the weight of the patient), although in the authors’ experience, the adjustment of needle length may often be overlooked (TABLE⁷).

The majority of reported SIRVA cases caused by overpenetration have occurred in individuals weighing <140 lb or those who had little deltoid muscle bulk. An MRI study to evaluate optimal intramuscular needle length in pediatric patients found that the IAC-recommended needle lengths still allowed penetration of the subdeltoid space in a substantial number of patients.⁸ Classic teaching of IM deltoid injection landmarks is 3 fingerbreadths distal to the acromion, and a more proximal administration of a vaccine would allow penetration of the rotator cuff structures below.

How to manage the patient

Patients who develop SIRVA should be managed similarly to patients with tendinopathy from other causes. Treatment options include: physical therapy, anti-inflammatory medications, and subacromial corticosteroid injections. Given the significant discomfort and nighttime pain associated with rotator cuff tendinopathy, corticosteroid injections can offer rapid relief.

Limited data exist on the effect of corticosteroids on the suppression of the immune response in immunocompetent patients. Vaccinations are generally thought to stimulate an adequate immune response 14 days following administration, so our suggestion would be to re-vaccinate patients if a corticosteroid injection to treat SIRVA is completed prior to this.⁹

Our patient’s outcome

We talked to the patient about treatment options, which included physical therapy and nonsteroidal anti-inflammatory drugs (NSAIDs), but the patient elected to go forward with a corticosteroid injection. We administered 2 cc of Depo-Medrol 40 mg/mL with 2 cc of 1% lidocaine without epinephrine and 2 cc of 0.5% ropivacaine into her right shoulder subacromial space using a posterior approach. The patient noticed a 70% improvement in her pain immediately following the injection.

Continue to: Considering her influenza vaccine...

Considering her influenza vaccine was administered more than 14 days prior to her corticosteroid injection, we felt that she had mounted enough of an immune response for the vaccination to have been adequate for protection.⁹ Therefore, we told her that she didn’t need to be revaccinated for influenza this season. The case was reported to the Vaccine Adverse Event Reporting System (VAERS).

In previous cases of vaccine-associated rotator cuff tendonopathy, T2 MRI images have shown focal inflammatory signal within the supraspinatous tendon and subacromial bursa.

At the patient’s 2-month follow up, she reported an overall 80% improvement in pain. She continued to have occasional discomfort with certain movements, although the pain was relieved with over-the-counter anti-inflammatory medication. On physical exam she had an intact arc of abduction of the right shoulder to 150° without pain. Forward flexion and external and internal rotation were normal and pain free. She had mild pain with resisted abduction and a positive Hawkin’s test. The patient agreed to go to physical therapy to work on rotator cuff strengthening. She denied any known influenza infection up to that time.

THE TAKEAWAY

It’s important to consider rotator cuff injuries or SIRVA as a potential adverse effect of influenza vaccination administration. Thin patients and those with low deltoid muscle mass are at risk of vaccine over-penetration, and proximally placed deltoid vaccines may reach the rotator cuff structures below. Staff should be trained on appropriate techniques for administering influenza vaccinations to avoid causing SIRVA. Specifically:

• Intramuscular vaccines injected into the deltoid muscle should be 3 fingerbreadths distal to the acromion. A more proximal approach could potentially contact the rotator cuff muscles.
• Vaccine administration should mirror the position of the patient (eg, if the patient is sitting, the administrator should be sitting; if the patient is standing, the administrator should be standing).
• Needle length for vaccine administration should be adjusted according to the patient’s weight (TABLE⁷).

Following vaccination, it is important to keep 2 other points in mind. First, if a subacromial corticosteroid injection is used for treatment of SIRVA within the first 2 weeks of vaccine administration, consider revaccination. Second, be sure to use the VAERS to report any clinically significant medical event that occurs after vaccination. VAERS is a national vaccine safety surveillance program that is supported by the CDC and the US Food and Drug Administration. The VAERS reporting system can be accessed through www.vaers.hhhs.gov.

CORRESPONDENCE
Dusty Marie Narducci, MD, 5290 Big Island Drive, Unit 1303, Jacksonville, FL 32246; [email protected]

THE CASE

A 61-year-old Caucasian woman presented with acute right shoulder pain that began after she received an influenza vaccination at a local pharmacy 2 weeks earlier. She pointed to the proximal-most aspect of her lateral right upper arm as the vaccination site. Her pain intensified with shoulder abduction, forward flexion, and reaching movements. She denied recent and past injury to her shoulder, fever, chills, rash, or skin changes at the injection site. She said her left shoulder did not bother her.

The patient had continued to participate in her aerobics class, despite the discomfort. Her medical history included hypertension and myocardial infarction, and the medications she was taking included lisinopril 20 mg/d, atenolol 50 mg/d, and aspirin 81 mg/d.

The physical exam revealed a thin female with no visible rashes or erythema on her right shoulder. While there was no deltoid atrophy in comparison to her unaffected shoulder, she generally had low muscle mass in both arms. A painful arc of abduction was present, as was pain with palpation of the supraspinatus insertion. No pain was appreciated over the short or long head of the biceps tendon or the sternoclavicular or acromioclavicular joints. Strength was 5/5 for all movements of the rotator cuff, but pain was reproduced with resisted shoulder abduction. A Hawkin’s test was positive, while Speed’s, Yergason’s, cross-arm abduction, and O’Brien’s tests were all negative.

THE DIAGNOSIS

Anteroposterior, Grashey, Y-view, and axillary view radiographs of the right shoulder were normal without any calcific tendinopathy, degenerative changes, or acute fractures. The patient’s history and physical exam were consistent with a rotator cuff tendinitis secondary to an immune response to an influenza vaccination that infiltrated the supraspinatus tendon.

DISCUSSION

Soreness, redness and swelling at the injection site, fever, body aches, and headache are common adverse effects of the influenza vaccine.¹Although rare, acute brachial neuritis, infection, rotator cuff injuries, and contusions of the humeral head have also been reported. ^2-5 Collectively, these conditions are referred to as shoulder injuries related to vaccination administration (SIRVA). There have been multiple SIRVA cases reported in the United States, and the US Court of Federal Claims has compensated >100 patients for SIRVA since 2011.⁶ There is currently no listing of SIRVA as a potential adverse reaction to the influenza vaccine on the package inserts or on the Centers for Disease Control and Prevention (CDC) Web site.

Shoulder soreness lasting <72 hours without functional impairment is likely due to soreness at the injection site. If symptoms do not resolve within 72 to 96 hours, consider a more thorough workup, with SIRVA being a possible diagnosis.^1,7 The etiology of SIRVA remains uncertain, but an inflammatory reaction from a vaccine mistakenly administered into the subacromial/subdeltoid bursa has been suggested. Whether this reaction is dependent on the nonantigenic or antigenic components of the vaccine has yet to be determined.

Symptoms of SIRVA include pain with arm movement, pain that is worse at night or awakens the patient from sleep, restricted range of motion, or arm weakness. Examination will reveal pain when resisting rotator cuff movements, particularly shoulder abduction. Advanced imaging can be considered when the diagnosis is in question. In previous cases of vaccine-associated rotator cuff tendinopathy in the authors’ practice, T2 magnetic resonance imaging (MRI) has shown focal inflammatory signal within the supraspinatus tendon and subacromial bursa.

Continue to: With support from the CDC...

With support from the CDC, the Immunization Action Coalition (IAC), a source of immunization information for health care professionals, recommends that vaccines be administered into the deltoid or vastus lateralis for individuals between the ages of 3 and 18 years and recommends the deltoid as the preferred location in adults ≥19 years. The IAC suggests increasing the needle length for intramuscular (IM) immunizations (depending on the weight of the patient), although in the authors’ experience, the adjustment of needle length may often be overlooked (TABLE⁷).

The majority of reported SIRVA cases caused by overpenetration have occurred in individuals weighing <140 lb or those who had little deltoid muscle bulk. An MRI study to evaluate optimal intramuscular needle length in pediatric patients found that the IAC-recommended needle lengths still allowed penetration of the subdeltoid space in a substantial number of patients.⁸ Classic teaching of IM deltoid injection landmarks is 3 fingerbreadths distal to the acromion, and a more proximal administration of a vaccine would allow penetration of the rotator cuff structures below.

How to manage the patient

Patients who develop SIRVA should be managed similarly to patients with tendinopathy from other causes. Treatment options include: physical therapy, anti-inflammatory medications, and subacromial corticosteroid injections. Given the significant discomfort and nighttime pain associated with rotator cuff tendinopathy, corticosteroid injections can offer rapid relief.

Limited data exist on the effect of corticosteroids on the suppression of the immune response in immunocompetent patients. Vaccinations are generally thought to stimulate an adequate immune response 14 days following administration, so our suggestion would be to re-vaccinate patients if a corticosteroid injection to treat SIRVA is completed prior to this.⁹

Our patient’s outcome

We talked to the patient about treatment options, which included physical therapy and nonsteroidal anti-inflammatory drugs (NSAIDs), but the patient elected to go forward with a corticosteroid injection. We administered 2 cc of Depo-Medrol 40 mg/mL with 2 cc of 1% lidocaine without epinephrine and 2 cc of 0.5% ropivacaine into her right shoulder subacromial space using a posterior approach. The patient noticed a 70% improvement in her pain immediately following the injection.

Continue to: Considering her influenza vaccine...

Considering her influenza vaccine was administered more than 14 days prior to her corticosteroid injection, we felt that she had mounted enough of an immune response for the vaccination to have been adequate for protection.⁹ Therefore, we told her that she didn’t need to be revaccinated for influenza this season. The case was reported to the Vaccine Adverse Event Reporting System (VAERS).

In previous cases of vaccine-associated rotator cuff tendonopathy, T2 MRI images have shown focal inflammatory signal within the supraspinatous tendon and subacromial bursa.

At the patient’s 2-month follow up, she reported an overall 80% improvement in pain. She continued to have occasional discomfort with certain movements, although the pain was relieved with over-the-counter anti-inflammatory medication. On physical exam she had an intact arc of abduction of the right shoulder to 150° without pain. Forward flexion and external and internal rotation were normal and pain free. She had mild pain with resisted abduction and a positive Hawkin’s test. The patient agreed to go to physical therapy to work on rotator cuff strengthening. She denied any known influenza infection up to that time.

THE TAKEAWAY

It’s important to consider rotator cuff injuries or SIRVA as a potential adverse effect of influenza vaccination administration. Thin patients and those with low deltoid muscle mass are at risk of vaccine over-penetration, and proximally placed deltoid vaccines may reach the rotator cuff structures below. Staff should be trained on appropriate techniques for administering influenza vaccinations to avoid causing SIRVA. Specifically:

• Intramuscular vaccines injected into the deltoid muscle should be 3 fingerbreadths distal to the acromion. A more proximal approach could potentially contact the rotator cuff muscles.
• Vaccine administration should mirror the position of the patient (eg, if the patient is sitting, the administrator should be sitting; if the patient is standing, the administrator should be standing).
• Needle length for vaccine administration should be adjusted according to the patient’s weight (TABLE⁷).

Following vaccination, it is important to keep 2 other points in mind. First, if a subacromial corticosteroid injection is used for treatment of SIRVA within the first 2 weeks of vaccine administration, consider revaccination. Second, be sure to use the VAERS to report any clinically significant medical event that occurs after vaccination. VAERS is a national vaccine safety surveillance program that is supported by the CDC and the US Food and Drug Administration. The VAERS reporting system can be accessed through www.vaers.hhhs.gov.

CORRESPONDENCE
Dusty Marie Narducci, MD, 5290 Big Island Drive, Unit 1303, Jacksonville, FL 32246; [email protected]

Sarcoidosis is a systemic inflammatory condition with pulmonary and extrapulmonary manifestations. The etiology of sarcoidosis remains unknown. Iannuzzi and colleagues hypothesize that an unknown antigen sets off a cycle of chronic granulomatous inflammation in a genetically susceptible host.¹

Diagnosis

A diagnosis of sarcoidosis is typically based on a patient having an appropriate clinical presentation and a biopsy, often of lungs or skin, showing noncaseating granulomas.

Symptoms

Of the protean manifestations of sarcoidosis, respiratory symptoms are the most common and typically include subacute or chronic cough and progressive dyspnea on exertion.² Chest imaging may show only hilar or mediastinal lymphadenopathy, diffuse micronodular lung disease, or signs of chronic inflammation and fibrosis.² Upper airway involvement and progressive lung disease may lead to increased risk of sleep-disordered breathing, particularly obstructive sleep apnea (OSA).³

Sarcoidosis also can develop in the skin, neurologic system, heart, and other systems. It typically presents as areas of patchy, infiltrative inflammation. In the heart, this can lead to heart failure, often with reduced ejection fraction (EF) and ventricular arrhythmias.¹ Pulmonary hypertension (PH) may result from multiple possible mechanisms, including left-heart disease, parenchymal lung disease, sleep-disordered breathing, and possibly direct inflammation and compression of the pulmonary vasculature.^2-4

Sarcoidosis in Obese Patients

Emerging evidence shows that sarcoidosis occurs at higher rates in obese patients, suggesting that obesity may be a risk factor for the disease.^5-7 Rates of morbid obesity are increasing in the US. From 2000 to 2010, the prevalence of morbid obesity, defined as body mass index (BMI) > 40, increased by 70%, with even larger relative increases in the number of patients with BMI > 50.⁸ Among veterans who receive health care at the US Department of Veterans Affairs (VA) medical centers, 28% are obese.⁹ As a result, VA physicians will encounter more patients with morbid obesity and another significant comorbid condition.

Managing symptomatic sarcoidosis in patients with morbid obesity poses a dilemma. Typical treatment for symptomatic pulmonary sarcoidosis is prednisone 20 mg to 40 mg daily.^10,11 Higher doses are suggested for involvement of other organs, such as the heart.^2,12 Associated weight gain from corticosteroid treatment with possible sleep-disordered breathing increases an already high risk of metabolic complications in morbidly obese patients.¹³ No clear consensus exists on how corticosteroid doses should be adjusted. We present 2 cases that highlight the complexity of corticosteroid management in the obese sarcoidosis patient.

Case 1: Pulmonary Sarcoidosis

A 43-year-old morbidly obese man presented to his primary care provider with subacute onset of dyspnea. He had a history of OSA that was diagnosed empirically at another institution without polysomnogram and treated with autotitrating continuous positive airway pressure (CPAP).

The patient was admitted for expedited evaluation. His BMI was 63.2 with declining exercise tolerance and hypoxemia on ambulation. His oxyhemoglobin saturation rate was 85% after walking a short distance. Ongoing CPAP therapy for sleep-disordered breathing made laboratory evaluation for obesity hypoventilation syndrome (OHS) challenging. The patient’s serum bicarbonate test result was normal. Serum markers as well as induced sputum stains and cultures were negative for evidence of mycobacterial or fungal infections. A chest radiograph showed bilateral hilar adenopathy and miliary nodularity. Pulmonary function testing revealed severe obstruction and restriction as well as a moderate diffusion impairment. Bronchoscopy with biopsy revealed noncaseating granulomas consistent with sarcoidosis. An electrocardiogram (ECG) was normal. Transthoracic echocardiogram showed evidence of diastolic dysfunction and a mildly dilated right ventricle with normal function, suggestive of possible PH. We were unable to assess his pulmonary artery pressure.

Upon release, the patient began a course of 50 mg (0.24 mg/kg actual body weight) oral prednisone daily and home oxygen.

Six weeks after initiation of steroids, the patient reported that his dyspnea had improved. However, after 6 months of steroid treatment, his weight increased from 462 pounds to 503 pounds. He was evaluated for possible neurosarcoidosis with hypothalamic or pituitary involvement as a possible cause for the weight gain. Brain magnetic resonance imaging and hormonal testing were normal. We considered starting him on a steroid-sparing agent. However, after early efficacy, prednisone was gradually tapered and, after 1 year of treatment, discontinued. At that time, symptoms had substantially improved: His pulmonary function tests had normalized, and he was weaned off oxygen; repeat chest imaging showed only residual enlargement of the hilar lymph nodes. After cessation of steroids, the patient was able to lose 20 pounds.

Case 2: Cardiac Sarcoidosis

A 57-year-old morbidly obese man presented to the emergency department with subacute increasing dyspnea on exertion. He had a known history of sarcoidosis diagnosed by skin biopsy 28 years earlier but had been without treatment for decades. His history also included prediabetes, heart failure with preserved ejection fraction (HFpEF), OSA with an apnea hypopnea index (AHI) of 114.7 per hour, PH diagnosed by prior echocardiogram, and paroxysmal atrial fibrillation (AF). He required 2 L/m home oxygen and bilevel positive airway pressure (PAP) of 22/17 cm H₂O while sleeping.

On physical examination, the patient’s BMI was 54.6. He was tachycardic and hypoxemic on his usual oxygen flow rate. His serum bicarbonate, arterial blood pH, and PaCO₂ blood levels were normal. We heard bibasilar crackles over the lungs. Chest radiograph revealed an enlarged cardiac silhouette and bilateral infiltrates concerning for cardiogenic pulmonary edema. An echocardiogram showed a restrictive filling pattern with preserved EF and moderate dilation and dysfunction of the right ventricle, consistent with PH. A positron emission tomography (PET)/computed tomography scan, the preferred study for cardiac sarcoidosis, suggested active infiltrative septal cardiac disease and active hilar and mediastinal adenopathy. This was concerning for both cardiac and pulmonary sarcoidosis. Ongoing treatment of sleep-disordered breathing made laboratory assessment for OHS challenging. Given his intact EF, the absence of ventricular arrhythmias, and improvement with diuretics and bilevel PAP, specific treatment of sarcoidosis was not initiated. He was discharged home with a plan to re-evaluate sarcoidosis symptoms and initiate treatment as an outpatient.

The patient was readmitted 2 weeks later with worsened dyspnea, hypoxemia, and volume overload. A right heart catheterization confirmed PH with a mean pulmonary artery pressure of 44 mm Hg (68/32 mm Hg) and pulmonary vascular resistance of 4.6 Wood units. We also found evidence of left-heart dysfunction with a pulmonary capillary wedge pressure of 16 mm Hg.

Given his recurrent symptoms, evidence of active myocardial inflammation on recent PET, and prior biopsy-proven sarcoidosis, we made the decision to pursue treatment for symptomatic sarcoidosis. He began a course of 40 mg (0.20 mg/kg actual body weight) oral prednisone daily. He now required 6 L/m supplemental oxygen. After IV diuretic therapy during his hospitalization, the patient was discharged on his preadmission oral diuretic dose. Pulmonary vasodilator therapy was not initiated for PH as left heart disease and sleep-disordered breathing needed to be managed first.

One month after steroid initiation, the patient reported that the dyspnea and hypoxemia had markedly improved. His oxygen flow rate was reduced to 2 L/m. He remained normotensive and had no further difficulties with fluid retention or volume overload on a stable dose of oral diuretics. He had elevated blood glucose with a glycated hemoglobin (HbA_1c) of 6.4%. He began treatment with glipizide 5 mg daily.

After 3 months, he returned to the emergency department with hyperosmolar nonketotic hyperglycemia due to steroid-induced diabetes mellitus (DM). His HbA_1c was now 17.1%. The patient was started on a home insulin regimen, and his blood sugar values subsequently improved. He remained symptomatically better and lost 40 pounds with a guided weight management program and a stable diuretic regimen. He underwent arrhythmia evaluation with a Holter monitor that showed AF without ventricular arrhythmias.

Unfortunately, he did not return for cardiac or pulmonary reevaluation, and was lost to follow-up. Nine months after initiation of treatment, the patient died after an out-of-hospital cardiac arrest.

Discussion

These 2 cases highlight therapeutic challenges that may arise in the management of sarcoidosis with symptomatic vital organ involvement and coexistent extreme obesity. Both patients showed symptom improvement with moderate doses of prednisone (40 mg to 50 mg daily), but serious treatment-related complications developed: further weight gain in the first patient, and severe DM in the second. Although DM may have been a direct treatment complication in our second patient, his HFpEF and PH were high-risk comorbidities; he did not present with acute symptomatic worsening after treatment initiation. His symptoms were never reassessed when he was lost to follow-up.

Sarcoidosis/Obesity Relationship

Recent evidence suggests that patients with obesity are at increased risk of developing sarcoidosis.^5-7 Although the mechanism of association is unclear, several possibilities have been proposed.

Neurosarcoidosis. One known but rare cause of obesity is neurosarcoidosis of the hypothalamus or pituitary.¹⁴ This was investigated in one of our patients.

Proinflammatory responses. Another possible mechanism for the association of sarcoidosis and obesity is the proinflammatory properties of increased fat and adipose tissue.¹⁵ Obesity has been linked to an aberrant expansion of inflammatory cells and mediators, including macrophages, proinflammatory cytokines, T cells, and B cells.¹⁵ Leptin, produced primarily by adipocytes, also is higher in obese patients and has been found to be proinflammatory.¹⁶ These seem to underlie the link between obesity and other inflammatory diseases, including type 2 DM, gout, and atherosclerosis.¹⁵

Behavioral link. There also is a possible behavioral link between sarcoidosis and obesity: A patient might develop symptomatic sarcoidosis and later become less active due to dyspnea, which could predispose to weight gain.⁵

Management of Comorbid Sarcoidosis and Obesity

Regardless of the exact mechanism of this association, management of the co-occurrence of sarcoidosis and obesity poses a clinical problem, especially in cases of extreme obesity. Corticosteroids are generally considered the treatment of choice for symptomatic sarcoidosis. The initial treatment of symptomatic pulmonary sarcoidosis is 20 mg to 40 mg prednisone daily.^10,11 Higher daily doses such as 60 mg to 80 mg or 0.5 mg/kg are typically used to treat cardiac sarcoidosis, although no clear consensus exists on the appropriate dose.^12,17 One recent study showed no difference in cardiac outcomes in patients treated with high- and low-dose prednisone.¹⁸

For patients who are obese and require steroids to treat a medical condition, there is conflicting evidence on whether steroid doses should be increased in proportion to total body weight. Milsap and colleagues found clearance of prednisolone correlated strongly with degree of obesity, suggesting steroid dose should be increased in accordance with actual weight.¹⁹ In contrast, Dunn and colleagues found decreased clearance of methylprednisolone in obese patients, suggesting that ideal body weight dosing is appropriate.²⁰

Identifying the appropriate steroid dose is important because corticosteroids place obese patients at higher risk of developing complications. Treatment-related comorbidities include DM, hypertension, fluid retention, osteoporosis, and infection. Further weight gain due to steroid use is a risk for progressive OSA and, even though not generally associated with sarcoidosis alone, OHS. For patients with sarcoidosis, these complications (DM, fluid retention, hypertension, sleep-disordered breathing) may increase the risk of cardiovascular disease and PH.^21-23 Cardiomyopathy, especially with reduced EF and increased PH, can be associated with a poor prognosis in sarcoidosis.^4,24-26 PH also can be challenging to treat patients with sarcoidosis because the response of PH to steroids is unclear.²⁷ Small trials have shown the benefit of pulmonary vasodilators on hemodynamics, but these have generally been used in patients with stable sarcoidosis who do not have left-heart disease.^28-30

Our Prescription Model

We empirically prescribed moderate total doses of prednisone—although low on a mg/kg basis—to balance efficacy and the risk of adverse effects in these 2 morbidly obese patients. We also managed treatment-related complications with guided weight-management programs, CPAP, or noninvasive ventilation for sleep-disordered breathing, and DM treatment.

Our cases demonstrate the need for close monitoring of weight, blood pressure, and blood glucose to detect and treat any complications that may arise during corticosteroid treatment. Aggressive treatment of hyperglycemia with insulin or oral alternatives associated with weight loss such as metformin, sulfonylureas, dipeptidyl peptidase 4 inhibitors, or glucagon-like peptide 1 receptor agonists, may help prevent further DM complications. Sleep-disordered breathing should be assessed and treated. Bariatric surgery may be an option to treat obesity and minimize resultant complications. In our patients, and likely many others, the degree of respiratory and cardiac disease coupled with poor wound healing due to chronic prednisone, may increase the procedural risks.

Conclusion

Our experiences with these patients illustrate that symptomatic and objective improvement in sarcoidosis may be achieved in morbidly obese patients with doses of prednisone that are generally considered moderate, though quite low on a mg/kg basis.

We believe ours is the first report to describe the use of corticosteroids for the treatment of sarcoidosis in patients with morbid obesity. That 2 patients were treated at a single VA medical center within 1-year likely reflects the rising incidence of morbid obesity in the US veteran population and suggests that other federal practitioners might encounter similar patients.

Further study may show that, as an alternative to initial moderate-dose prednisone, patients with symptomatic sarcoidosis and extreme obesity might be started on antimetabolite or antitumor necrosis factor medication or on low-dose prednisone and a second steroid-sparing agent.

Sarcoidosis is a systemic inflammatory condition with pulmonary and extrapulmonary manifestations. The etiology of sarcoidosis remains unknown. Iannuzzi and colleagues hypothesize that an unknown antigen sets off a cycle of chronic granulomatous inflammation in a genetically susceptible host.¹

Diagnosis

A diagnosis of sarcoidosis is typically based on a patient having an appropriate clinical presentation and a biopsy, often of lungs or skin, showing noncaseating granulomas.

Symptoms

Of the protean manifestations of sarcoidosis, respiratory symptoms are the most common and typically include subacute or chronic cough and progressive dyspnea on exertion.² Chest imaging may show only hilar or mediastinal lymphadenopathy, diffuse micronodular lung disease, or signs of chronic inflammation and fibrosis.² Upper airway involvement and progressive lung disease may lead to increased risk of sleep-disordered breathing, particularly obstructive sleep apnea (OSA).³

Sarcoidosis also can develop in the skin, neurologic system, heart, and other systems. It typically presents as areas of patchy, infiltrative inflammation. In the heart, this can lead to heart failure, often with reduced ejection fraction (EF) and ventricular arrhythmias.¹ Pulmonary hypertension (PH) may result from multiple possible mechanisms, including left-heart disease, parenchymal lung disease, sleep-disordered breathing, and possibly direct inflammation and compression of the pulmonary vasculature.^2-4

Sarcoidosis in Obese Patients

Emerging evidence shows that sarcoidosis occurs at higher rates in obese patients, suggesting that obesity may be a risk factor for the disease.^5-7 Rates of morbid obesity are increasing in the US. From 2000 to 2010, the prevalence of morbid obesity, defined as body mass index (BMI) > 40, increased by 70%, with even larger relative increases in the number of patients with BMI > 50.⁸ Among veterans who receive health care at the US Department of Veterans Affairs (VA) medical centers, 28% are obese.⁹ As a result, VA physicians will encounter more patients with morbid obesity and another significant comorbid condition.

Managing symptomatic sarcoidosis in patients with morbid obesity poses a dilemma. Typical treatment for symptomatic pulmonary sarcoidosis is prednisone 20 mg to 40 mg daily.^10,11 Higher doses are suggested for involvement of other organs, such as the heart.^2,12 Associated weight gain from corticosteroid treatment with possible sleep-disordered breathing increases an already high risk of metabolic complications in morbidly obese patients.¹³ No clear consensus exists on how corticosteroid doses should be adjusted. We present 2 cases that highlight the complexity of corticosteroid management in the obese sarcoidosis patient.

Case 1: Pulmonary Sarcoidosis

A 43-year-old morbidly obese man presented to his primary care provider with subacute onset of dyspnea. He had a history of OSA that was diagnosed empirically at another institution without polysomnogram and treated with autotitrating continuous positive airway pressure (CPAP).

The patient was admitted for expedited evaluation. His BMI was 63.2 with declining exercise tolerance and hypoxemia on ambulation. His oxyhemoglobin saturation rate was 85% after walking a short distance. Ongoing CPAP therapy for sleep-disordered breathing made laboratory evaluation for obesity hypoventilation syndrome (OHS) challenging. The patient’s serum bicarbonate test result was normal. Serum markers as well as induced sputum stains and cultures were negative for evidence of mycobacterial or fungal infections. A chest radiograph showed bilateral hilar adenopathy and miliary nodularity. Pulmonary function testing revealed severe obstruction and restriction as well as a moderate diffusion impairment. Bronchoscopy with biopsy revealed noncaseating granulomas consistent with sarcoidosis. An electrocardiogram (ECG) was normal. Transthoracic echocardiogram showed evidence of diastolic dysfunction and a mildly dilated right ventricle with normal function, suggestive of possible PH. We were unable to assess his pulmonary artery pressure.

Upon release, the patient began a course of 50 mg (0.24 mg/kg actual body weight) oral prednisone daily and home oxygen.

Six weeks after initiation of steroids, the patient reported that his dyspnea had improved. However, after 6 months of steroid treatment, his weight increased from 462 pounds to 503 pounds. He was evaluated for possible neurosarcoidosis with hypothalamic or pituitary involvement as a possible cause for the weight gain. Brain magnetic resonance imaging and hormonal testing were normal. We considered starting him on a steroid-sparing agent. However, after early efficacy, prednisone was gradually tapered and, after 1 year of treatment, discontinued. At that time, symptoms had substantially improved: His pulmonary function tests had normalized, and he was weaned off oxygen; repeat chest imaging showed only residual enlargement of the hilar lymph nodes. After cessation of steroids, the patient was able to lose 20 pounds.

Case 2: Cardiac Sarcoidosis

A 57-year-old morbidly obese man presented to the emergency department with subacute increasing dyspnea on exertion. He had a known history of sarcoidosis diagnosed by skin biopsy 28 years earlier but had been without treatment for decades. His history also included prediabetes, heart failure with preserved ejection fraction (HFpEF), OSA with an apnea hypopnea index (AHI) of 114.7 per hour, PH diagnosed by prior echocardiogram, and paroxysmal atrial fibrillation (AF). He required 2 L/m home oxygen and bilevel positive airway pressure (PAP) of 22/17 cm H₂O while sleeping.

On physical examination, the patient’s BMI was 54.6. He was tachycardic and hypoxemic on his usual oxygen flow rate. His serum bicarbonate, arterial blood pH, and PaCO₂ blood levels were normal. We heard bibasilar crackles over the lungs. Chest radiograph revealed an enlarged cardiac silhouette and bilateral infiltrates concerning for cardiogenic pulmonary edema. An echocardiogram showed a restrictive filling pattern with preserved EF and moderate dilation and dysfunction of the right ventricle, consistent with PH. A positron emission tomography (PET)/computed tomography scan, the preferred study for cardiac sarcoidosis, suggested active infiltrative septal cardiac disease and active hilar and mediastinal adenopathy. This was concerning for both cardiac and pulmonary sarcoidosis. Ongoing treatment of sleep-disordered breathing made laboratory assessment for OHS challenging. Given his intact EF, the absence of ventricular arrhythmias, and improvement with diuretics and bilevel PAP, specific treatment of sarcoidosis was not initiated. He was discharged home with a plan to re-evaluate sarcoidosis symptoms and initiate treatment as an outpatient.

The patient was readmitted 2 weeks later with worsened dyspnea, hypoxemia, and volume overload. A right heart catheterization confirmed PH with a mean pulmonary artery pressure of 44 mm Hg (68/32 mm Hg) and pulmonary vascular resistance of 4.6 Wood units. We also found evidence of left-heart dysfunction with a pulmonary capillary wedge pressure of 16 mm Hg.

Given his recurrent symptoms, evidence of active myocardial inflammation on recent PET, and prior biopsy-proven sarcoidosis, we made the decision to pursue treatment for symptomatic sarcoidosis. He began a course of 40 mg (0.20 mg/kg actual body weight) oral prednisone daily. He now required 6 L/m supplemental oxygen. After IV diuretic therapy during his hospitalization, the patient was discharged on his preadmission oral diuretic dose. Pulmonary vasodilator therapy was not initiated for PH as left heart disease and sleep-disordered breathing needed to be managed first.

One month after steroid initiation, the patient reported that the dyspnea and hypoxemia had markedly improved. His oxygen flow rate was reduced to 2 L/m. He remained normotensive and had no further difficulties with fluid retention or volume overload on a stable dose of oral diuretics. He had elevated blood glucose with a glycated hemoglobin (HbA_1c) of 6.4%. He began treatment with glipizide 5 mg daily.

After 3 months, he returned to the emergency department with hyperosmolar nonketotic hyperglycemia due to steroid-induced diabetes mellitus (DM). His HbA_1c was now 17.1%. The patient was started on a home insulin regimen, and his blood sugar values subsequently improved. He remained symptomatically better and lost 40 pounds with a guided weight management program and a stable diuretic regimen. He underwent arrhythmia evaluation with a Holter monitor that showed AF without ventricular arrhythmias.

Unfortunately, he did not return for cardiac or pulmonary reevaluation, and was lost to follow-up. Nine months after initiation of treatment, the patient died after an out-of-hospital cardiac arrest.

Discussion

These 2 cases highlight therapeutic challenges that may arise in the management of sarcoidosis with symptomatic vital organ involvement and coexistent extreme obesity. Both patients showed symptom improvement with moderate doses of prednisone (40 mg to 50 mg daily), but serious treatment-related complications developed: further weight gain in the first patient, and severe DM in the second. Although DM may have been a direct treatment complication in our second patient, his HFpEF and PH were high-risk comorbidities; he did not present with acute symptomatic worsening after treatment initiation. His symptoms were never reassessed when he was lost to follow-up.

Sarcoidosis/Obesity Relationship

Recent evidence suggests that patients with obesity are at increased risk of developing sarcoidosis.^5-7 Although the mechanism of association is unclear, several possibilities have been proposed.

Neurosarcoidosis. One known but rare cause of obesity is neurosarcoidosis of the hypothalamus or pituitary.¹⁴ This was investigated in one of our patients.

Proinflammatory responses. Another possible mechanism for the association of sarcoidosis and obesity is the proinflammatory properties of increased fat and adipose tissue.¹⁵ Obesity has been linked to an aberrant expansion of inflammatory cells and mediators, including macrophages, proinflammatory cytokines, T cells, and B cells.¹⁵ Leptin, produced primarily by adipocytes, also is higher in obese patients and has been found to be proinflammatory.¹⁶ These seem to underlie the link between obesity and other inflammatory diseases, including type 2 DM, gout, and atherosclerosis.¹⁵

Behavioral link. There also is a possible behavioral link between sarcoidosis and obesity: A patient might develop symptomatic sarcoidosis and later become less active due to dyspnea, which could predispose to weight gain.⁵

Management of Comorbid Sarcoidosis and Obesity

Regardless of the exact mechanism of this association, management of the co-occurrence of sarcoidosis and obesity poses a clinical problem, especially in cases of extreme obesity. Corticosteroids are generally considered the treatment of choice for symptomatic sarcoidosis. The initial treatment of symptomatic pulmonary sarcoidosis is 20 mg to 40 mg prednisone daily.^10,11 Higher daily doses such as 60 mg to 80 mg or 0.5 mg/kg are typically used to treat cardiac sarcoidosis, although no clear consensus exists on the appropriate dose.^12,17 One recent study showed no difference in cardiac outcomes in patients treated with high- and low-dose prednisone.¹⁸

For patients who are obese and require steroids to treat a medical condition, there is conflicting evidence on whether steroid doses should be increased in proportion to total body weight. Milsap and colleagues found clearance of prednisolone correlated strongly with degree of obesity, suggesting steroid dose should be increased in accordance with actual weight.¹⁹ In contrast, Dunn and colleagues found decreased clearance of methylprednisolone in obese patients, suggesting that ideal body weight dosing is appropriate.²⁰

Identifying the appropriate steroid dose is important because corticosteroids place obese patients at higher risk of developing complications. Treatment-related comorbidities include DM, hypertension, fluid retention, osteoporosis, and infection. Further weight gain due to steroid use is a risk for progressive OSA and, even though not generally associated with sarcoidosis alone, OHS. For patients with sarcoidosis, these complications (DM, fluid retention, hypertension, sleep-disordered breathing) may increase the risk of cardiovascular disease and PH.^21-23 Cardiomyopathy, especially with reduced EF and increased PH, can be associated with a poor prognosis in sarcoidosis.^4,24-26 PH also can be challenging to treat patients with sarcoidosis because the response of PH to steroids is unclear.²⁷ Small trials have shown the benefit of pulmonary vasodilators on hemodynamics, but these have generally been used in patients with stable sarcoidosis who do not have left-heart disease.^28-30

Our Prescription Model

We empirically prescribed moderate total doses of prednisone—although low on a mg/kg basis—to balance efficacy and the risk of adverse effects in these 2 morbidly obese patients. We also managed treatment-related complications with guided weight-management programs, CPAP, or noninvasive ventilation for sleep-disordered breathing, and DM treatment.

Our cases demonstrate the need for close monitoring of weight, blood pressure, and blood glucose to detect and treat any complications that may arise during corticosteroid treatment. Aggressive treatment of hyperglycemia with insulin or oral alternatives associated with weight loss such as metformin, sulfonylureas, dipeptidyl peptidase 4 inhibitors, or glucagon-like peptide 1 receptor agonists, may help prevent further DM complications. Sleep-disordered breathing should be assessed and treated. Bariatric surgery may be an option to treat obesity and minimize resultant complications. In our patients, and likely many others, the degree of respiratory and cardiac disease coupled with poor wound healing due to chronic prednisone, may increase the procedural risks.

Conclusion

Our experiences with these patients illustrate that symptomatic and objective improvement in sarcoidosis may be achieved in morbidly obese patients with doses of prednisone that are generally considered moderate, though quite low on a mg/kg basis.

We believe ours is the first report to describe the use of corticosteroids for the treatment of sarcoidosis in patients with morbid obesity. That 2 patients were treated at a single VA medical center within 1-year likely reflects the rising incidence of morbid obesity in the US veteran population and suggests that other federal practitioners might encounter similar patients.

Further study may show that, as an alternative to initial moderate-dose prednisone, patients with symptomatic sarcoidosis and extreme obesity might be started on antimetabolite or antitumor necrosis factor medication or on low-dose prednisone and a second steroid-sparing agent.

Sarcoidosis is a systemic inflammatory condition with pulmonary and extrapulmonary manifestations. The etiology of sarcoidosis remains unknown. Iannuzzi and colleagues hypothesize that an unknown antigen sets off a cycle of chronic granulomatous inflammation in a genetically susceptible host.¹

Diagnosis

A diagnosis of sarcoidosis is typically based on a patient having an appropriate clinical presentation and a biopsy, often of lungs or skin, showing noncaseating granulomas.

Symptoms

Of the protean manifestations of sarcoidosis, respiratory symptoms are the most common and typically include subacute or chronic cough and progressive dyspnea on exertion.² Chest imaging may show only hilar or mediastinal lymphadenopathy, diffuse micronodular lung disease, or signs of chronic inflammation and fibrosis.² Upper airway involvement and progressive lung disease may lead to increased risk of sleep-disordered breathing, particularly obstructive sleep apnea (OSA).³

Sarcoidosis also can develop in the skin, neurologic system, heart, and other systems. It typically presents as areas of patchy, infiltrative inflammation. In the heart, this can lead to heart failure, often with reduced ejection fraction (EF) and ventricular arrhythmias.¹ Pulmonary hypertension (PH) may result from multiple possible mechanisms, including left-heart disease, parenchymal lung disease, sleep-disordered breathing, and possibly direct inflammation and compression of the pulmonary vasculature.^2-4

Sarcoidosis in Obese Patients

Emerging evidence shows that sarcoidosis occurs at higher rates in obese patients, suggesting that obesity may be a risk factor for the disease.^5-7 Rates of morbid obesity are increasing in the US. From 2000 to 2010, the prevalence of morbid obesity, defined as body mass index (BMI) > 40, increased by 70%, with even larger relative increases in the number of patients with BMI > 50.⁸ Among veterans who receive health care at the US Department of Veterans Affairs (VA) medical centers, 28% are obese.⁹ As a result, VA physicians will encounter more patients with morbid obesity and another significant comorbid condition.

Managing symptomatic sarcoidosis in patients with morbid obesity poses a dilemma. Typical treatment for symptomatic pulmonary sarcoidosis is prednisone 20 mg to 40 mg daily.^10,11 Higher doses are suggested for involvement of other organs, such as the heart.^2,12 Associated weight gain from corticosteroid treatment with possible sleep-disordered breathing increases an already high risk of metabolic complications in morbidly obese patients.¹³ No clear consensus exists on how corticosteroid doses should be adjusted. We present 2 cases that highlight the complexity of corticosteroid management in the obese sarcoidosis patient.

Case 1: Pulmonary Sarcoidosis

A 43-year-old morbidly obese man presented to his primary care provider with subacute onset of dyspnea. He had a history of OSA that was diagnosed empirically at another institution without polysomnogram and treated with autotitrating continuous positive airway pressure (CPAP).

The patient was admitted for expedited evaluation. His BMI was 63.2 with declining exercise tolerance and hypoxemia on ambulation. His oxyhemoglobin saturation rate was 85% after walking a short distance. Ongoing CPAP therapy for sleep-disordered breathing made laboratory evaluation for obesity hypoventilation syndrome (OHS) challenging. The patient’s serum bicarbonate test result was normal. Serum markers as well as induced sputum stains and cultures were negative for evidence of mycobacterial or fungal infections. A chest radiograph showed bilateral hilar adenopathy and miliary nodularity. Pulmonary function testing revealed severe obstruction and restriction as well as a moderate diffusion impairment. Bronchoscopy with biopsy revealed noncaseating granulomas consistent with sarcoidosis. An electrocardiogram (ECG) was normal. Transthoracic echocardiogram showed evidence of diastolic dysfunction and a mildly dilated right ventricle with normal function, suggestive of possible PH. We were unable to assess his pulmonary artery pressure.

Upon release, the patient began a course of 50 mg (0.24 mg/kg actual body weight) oral prednisone daily and home oxygen.

Six weeks after initiation of steroids, the patient reported that his dyspnea had improved. However, after 6 months of steroid treatment, his weight increased from 462 pounds to 503 pounds. He was evaluated for possible neurosarcoidosis with hypothalamic or pituitary involvement as a possible cause for the weight gain. Brain magnetic resonance imaging and hormonal testing were normal. We considered starting him on a steroid-sparing agent. However, after early efficacy, prednisone was gradually tapered and, after 1 year of treatment, discontinued. At that time, symptoms had substantially improved: His pulmonary function tests had normalized, and he was weaned off oxygen; repeat chest imaging showed only residual enlargement of the hilar lymph nodes. After cessation of steroids, the patient was able to lose 20 pounds.

Case 2: Cardiac Sarcoidosis

A 57-year-old morbidly obese man presented to the emergency department with subacute increasing dyspnea on exertion. He had a known history of sarcoidosis diagnosed by skin biopsy 28 years earlier but had been without treatment for decades. His history also included prediabetes, heart failure with preserved ejection fraction (HFpEF), OSA with an apnea hypopnea index (AHI) of 114.7 per hour, PH diagnosed by prior echocardiogram, and paroxysmal atrial fibrillation (AF). He required 2 L/m home oxygen and bilevel positive airway pressure (PAP) of 22/17 cm H₂O while sleeping.

On physical examination, the patient’s BMI was 54.6. He was tachycardic and hypoxemic on his usual oxygen flow rate. His serum bicarbonate, arterial blood pH, and PaCO₂ blood levels were normal. We heard bibasilar crackles over the lungs. Chest radiograph revealed an enlarged cardiac silhouette and bilateral infiltrates concerning for cardiogenic pulmonary edema. An echocardiogram showed a restrictive filling pattern with preserved EF and moderate dilation and dysfunction of the right ventricle, consistent with PH. A positron emission tomography (PET)/computed tomography scan, the preferred study for cardiac sarcoidosis, suggested active infiltrative septal cardiac disease and active hilar and mediastinal adenopathy. This was concerning for both cardiac and pulmonary sarcoidosis. Ongoing treatment of sleep-disordered breathing made laboratory assessment for OHS challenging. Given his intact EF, the absence of ventricular arrhythmias, and improvement with diuretics and bilevel PAP, specific treatment of sarcoidosis was not initiated. He was discharged home with a plan to re-evaluate sarcoidosis symptoms and initiate treatment as an outpatient.

The patient was readmitted 2 weeks later with worsened dyspnea, hypoxemia, and volume overload. A right heart catheterization confirmed PH with a mean pulmonary artery pressure of 44 mm Hg (68/32 mm Hg) and pulmonary vascular resistance of 4.6 Wood units. We also found evidence of left-heart dysfunction with a pulmonary capillary wedge pressure of 16 mm Hg.

Given his recurrent symptoms, evidence of active myocardial inflammation on recent PET, and prior biopsy-proven sarcoidosis, we made the decision to pursue treatment for symptomatic sarcoidosis. He began a course of 40 mg (0.20 mg/kg actual body weight) oral prednisone daily. He now required 6 L/m supplemental oxygen. After IV diuretic therapy during his hospitalization, the patient was discharged on his preadmission oral diuretic dose. Pulmonary vasodilator therapy was not initiated for PH as left heart disease and sleep-disordered breathing needed to be managed first.

One month after steroid initiation, the patient reported that the dyspnea and hypoxemia had markedly improved. His oxygen flow rate was reduced to 2 L/m. He remained normotensive and had no further difficulties with fluid retention or volume overload on a stable dose of oral diuretics. He had elevated blood glucose with a glycated hemoglobin (HbA_1c) of 6.4%. He began treatment with glipizide 5 mg daily.

After 3 months, he returned to the emergency department with hyperosmolar nonketotic hyperglycemia due to steroid-induced diabetes mellitus (DM). His HbA_1c was now 17.1%. The patient was started on a home insulin regimen, and his blood sugar values subsequently improved. He remained symptomatically better and lost 40 pounds with a guided weight management program and a stable diuretic regimen. He underwent arrhythmia evaluation with a Holter monitor that showed AF without ventricular arrhythmias.

Unfortunately, he did not return for cardiac or pulmonary reevaluation, and was lost to follow-up. Nine months after initiation of treatment, the patient died after an out-of-hospital cardiac arrest.

Discussion

These 2 cases highlight therapeutic challenges that may arise in the management of sarcoidosis with symptomatic vital organ involvement and coexistent extreme obesity. Both patients showed symptom improvement with moderate doses of prednisone (40 mg to 50 mg daily), but serious treatment-related complications developed: further weight gain in the first patient, and severe DM in the second. Although DM may have been a direct treatment complication in our second patient, his HFpEF and PH were high-risk comorbidities; he did not present with acute symptomatic worsening after treatment initiation. His symptoms were never reassessed when he was lost to follow-up.

Sarcoidosis/Obesity Relationship

Recent evidence suggests that patients with obesity are at increased risk of developing sarcoidosis.^5-7 Although the mechanism of association is unclear, several possibilities have been proposed.

Neurosarcoidosis. One known but rare cause of obesity is neurosarcoidosis of the hypothalamus or pituitary.¹⁴ This was investigated in one of our patients.

Proinflammatory responses. Another possible mechanism for the association of sarcoidosis and obesity is the proinflammatory properties of increased fat and adipose tissue.¹⁵ Obesity has been linked to an aberrant expansion of inflammatory cells and mediators, including macrophages, proinflammatory cytokines, T cells, and B cells.¹⁵ Leptin, produced primarily by adipocytes, also is higher in obese patients and has been found to be proinflammatory.¹⁶ These seem to underlie the link between obesity and other inflammatory diseases, including type 2 DM, gout, and atherosclerosis.¹⁵

Behavioral link. There also is a possible behavioral link between sarcoidosis and obesity: A patient might develop symptomatic sarcoidosis and later become less active due to dyspnea, which could predispose to weight gain.⁵

Management of Comorbid Sarcoidosis and Obesity

Regardless of the exact mechanism of this association, management of the co-occurrence of sarcoidosis and obesity poses a clinical problem, especially in cases of extreme obesity. Corticosteroids are generally considered the treatment of choice for symptomatic sarcoidosis. The initial treatment of symptomatic pulmonary sarcoidosis is 20 mg to 40 mg prednisone daily.^10,11 Higher daily doses such as 60 mg to 80 mg or 0.5 mg/kg are typically used to treat cardiac sarcoidosis, although no clear consensus exists on the appropriate dose.^12,17 One recent study showed no difference in cardiac outcomes in patients treated with high- and low-dose prednisone.¹⁸

For patients who are obese and require steroids to treat a medical condition, there is conflicting evidence on whether steroid doses should be increased in proportion to total body weight. Milsap and colleagues found clearance of prednisolone correlated strongly with degree of obesity, suggesting steroid dose should be increased in accordance with actual weight.¹⁹ In contrast, Dunn and colleagues found decreased clearance of methylprednisolone in obese patients, suggesting that ideal body weight dosing is appropriate.²⁰

Identifying the appropriate steroid dose is important because corticosteroids place obese patients at higher risk of developing complications. Treatment-related comorbidities include DM, hypertension, fluid retention, osteoporosis, and infection. Further weight gain due to steroid use is a risk for progressive OSA and, even though not generally associated with sarcoidosis alone, OHS. For patients with sarcoidosis, these complications (DM, fluid retention, hypertension, sleep-disordered breathing) may increase the risk of cardiovascular disease and PH.^21-23 Cardiomyopathy, especially with reduced EF and increased PH, can be associated with a poor prognosis in sarcoidosis.^4,24-26 PH also can be challenging to treat patients with sarcoidosis because the response of PH to steroids is unclear.²⁷ Small trials have shown the benefit of pulmonary vasodilators on hemodynamics, but these have generally been used in patients with stable sarcoidosis who do not have left-heart disease.^28-30

Our Prescription Model

We empirically prescribed moderate total doses of prednisone—although low on a mg/kg basis—to balance efficacy and the risk of adverse effects in these 2 morbidly obese patients. We also managed treatment-related complications with guided weight-management programs, CPAP, or noninvasive ventilation for sleep-disordered breathing, and DM treatment.

Our cases demonstrate the need for close monitoring of weight, blood pressure, and blood glucose to detect and treat any complications that may arise during corticosteroid treatment. Aggressive treatment of hyperglycemia with insulin or oral alternatives associated with weight loss such as metformin, sulfonylureas, dipeptidyl peptidase 4 inhibitors, or glucagon-like peptide 1 receptor agonists, may help prevent further DM complications. Sleep-disordered breathing should be assessed and treated. Bariatric surgery may be an option to treat obesity and minimize resultant complications. In our patients, and likely many others, the degree of respiratory and cardiac disease coupled with poor wound healing due to chronic prednisone, may increase the procedural risks.

Conclusion

Our experiences with these patients illustrate that symptomatic and objective improvement in sarcoidosis may be achieved in morbidly obese patients with doses of prednisone that are generally considered moderate, though quite low on a mg/kg basis.

We believe ours is the first report to describe the use of corticosteroids for the treatment of sarcoidosis in patients with morbid obesity. That 2 patients were treated at a single VA medical center within 1-year likely reflects the rising incidence of morbid obesity in the US veteran population and suggests that other federal practitioners might encounter similar patients.

Further study may show that, as an alternative to initial moderate-dose prednisone, patients with symptomatic sarcoidosis and extreme obesity might be started on antimetabolite or antitumor necrosis factor medication or on low-dose prednisone and a second steroid-sparing agent.

Case Report

A 26-year-old woman with a medical history of newly diagnosed diabetes mellitus (DM), obesity, and asthma was evaluated as a hospital consultation with a vegetative plaque on the left lateral ankle of 13 months’ duration. The lesion first appeared as a red scaly rash that became purulent. The lesion had been treated with multiple rounds of topical antibiotics, oral antibiotics, topical antifungals, and corticosteroids without resolution. The patient denied pain or any decrease in ankle mobility. Review of systems was otherwise negative.

On physical examination, 3 large, pink, scaly, crusted plaques with surrounding erythema were observed (Figure 1A). On palpation, purulent drainage with a foul odor was noted in the area underlying the lesion. Initial punch biopsy demonstrated epidermal hyperplasia with neutrophil-rich sinus tracts consistent with pyoderma vegetans (PV)(Figure 2A). Tissue culture was positive for Staphylococcus aureus and Streptococcus anginosus. Cultures for both fungi and acid-fast bacilli were negative for growth.

The patient was treated with mupirocin ointment 2% and 3 months of cephalexin 250 mg twice daily, which cleared the purulent crust; however, serous drainage, ulceration, and erythema persisted. The patient needed an extended course of antibiotics, which had not been previously administered to clear the purulence. During this treatment regimen, the patient’s DM remained uncontrolled.

A second deeper punch biopsy revealed a layered granulomatous infiltrate with sclerosis throughout the dermis most consistent with necrobiosis lipoidica (NL)(Figure 2B). Direct immunofluorescence biopsy was negative. Once the PV was clear, betamethasone dipropionate ointment 0.05% was initiated to address the residual lesions (Figure 1B).

Physical examination combined with histopathologic findings and staphylococcal- and streptococcal-positive tissue cultures supported a diagnosis of NL with superimposed PV.

Comment

Necrobiosis lipoidica is a chronic granulomatous disease characterized by collagen degeneration, granulomatous formation, and endothelial wall thickening.¹ The condition is most commonly seen in association with insulin-dependent DM, though it also has been described in other inflammatory conditions. A case of NL in monozygotic twins has been reported, suggesting a genetic component in nondiabetic patients with NL.² Necrobiosis lipoidica affects females more often than males.

The pathogenesis of NL is not well understood but likely involves secondary microangiopathy because of glycoprotein deposition in vessel walls, leading to vascular thickening. Histopathology reveals palisading and necrobiotic granulomas comprising large confluent areas of necrobiosis throughout the dermis, giving a layered appearance.³

Clinically, NL presents with asymptomatic, well-circumscribed, violaceous papules and nodules that coalesce into plaques on the lower extremities, face, or trunk. The plaques have a central red-brown hue that progressively becomes more yellow and atrophic. The lesions can become eroded and ulcerated if left untreated.¹

Clinical diagnosis of NL can be challenging due to the similar clinical findings of other granulomatous lesions, such as granuloma annulare and cutaneous sarcoidosis. As reported by Pellicano and colleagues,⁴ dermoscopy has proved to be an excellent tool for differentiating these granulomatous skin lesions. Necrobiosis lipoidica demonstrates elongated serpentine telangiectases overlying a white structureless background, whereas granuloma annulare reveals orange-red structureless peripheral borders.⁵

Treatment of NL is difficult; patients often are refractory. Tight control of blood glucose alone has not been proven to cure NL. The mainstay of treatment is topical and intralesional corticosteroids at the active borders of the lesions. Tumor necrosis factor α inhibitors have shown some success, though recurrence has been reported.⁶ Other treatments, such as topical tretinoin and topical tacrolimus, may be of some benefit for atrophic NL lesions. Studies also have shown that skin grafting can be of surgical benefit in ulcerative NL with a low rate of recurrence.⁶ Control and management of DM plus lifestyle modifications may play a role in decreasing the severity of NL.⁷ Topical psoralen plus UVA light therapy and other experimental treatments, such as antiplatelet medications,⁸ also have been utilized.

The case of NL presented here was complicated by a superimposed suppurative infection consistent with PV, a rare chronic bacterial infection of the skin that presents with vegetative plaques. Pyoderma vegetans is most commonly observed in patients with underlying immunosuppression, likely secondary to DM in this case. Pyoderma vegetans is most often caused by S aureus and β-hemolytic streptococci. The clinical presentation of PV reveals verrucous vegetative plaques with pustules and abscesses. The borders of the lesions may be elevated and have a granulomatous appearance, thus complicating clinical diagnosis. There often is foul-smelling, purulent discharge within the plaques.⁹

Histopathology reveals pseudoepitheliomatous hyperplasia with abscesses and sinus tracts. An acute or chronic granulomatous inflammatory infiltrate may be observed. Basophilic fungus like granules are not seen within specimens of PV, which helps differentiate the disease from botryomycosis.¹⁰

There is no standardized treatment of PV; topical and systemic antibiotics are mainstays.¹⁰ One reported case of PV responded well to acitretin.⁹ Our patient responded well to 3 months of oral antibiotic therapy, followed by topical corticosteroids.

Case Report

A 26-year-old woman with a medical history of newly diagnosed diabetes mellitus (DM), obesity, and asthma was evaluated as a hospital consultation with a vegetative plaque on the left lateral ankle of 13 months’ duration. The lesion first appeared as a red scaly rash that became purulent. The lesion had been treated with multiple rounds of topical antibiotics, oral antibiotics, topical antifungals, and corticosteroids without resolution. The patient denied pain or any decrease in ankle mobility. Review of systems was otherwise negative.

On physical examination, 3 large, pink, scaly, crusted plaques with surrounding erythema were observed (Figure 1A). On palpation, purulent drainage with a foul odor was noted in the area underlying the lesion. Initial punch biopsy demonstrated epidermal hyperplasia with neutrophil-rich sinus tracts consistent with pyoderma vegetans (PV)(Figure 2A). Tissue culture was positive for Staphylococcus aureus and Streptococcus anginosus. Cultures for both fungi and acid-fast bacilli were negative for growth.

The patient was treated with mupirocin ointment 2% and 3 months of cephalexin 250 mg twice daily, which cleared the purulent crust; however, serous drainage, ulceration, and erythema persisted. The patient needed an extended course of antibiotics, which had not been previously administered to clear the purulence. During this treatment regimen, the patient’s DM remained uncontrolled.

A second deeper punch biopsy revealed a layered granulomatous infiltrate with sclerosis throughout the dermis most consistent with necrobiosis lipoidica (NL)(Figure 2B). Direct immunofluorescence biopsy was negative. Once the PV was clear, betamethasone dipropionate ointment 0.05% was initiated to address the residual lesions (Figure 1B).

Physical examination combined with histopathologic findings and staphylococcal- and streptococcal-positive tissue cultures supported a diagnosis of NL with superimposed PV.

Comment

Necrobiosis lipoidica is a chronic granulomatous disease characterized by collagen degeneration, granulomatous formation, and endothelial wall thickening.¹ The condition is most commonly seen in association with insulin-dependent DM, though it also has been described in other inflammatory conditions. A case of NL in monozygotic twins has been reported, suggesting a genetic component in nondiabetic patients with NL.² Necrobiosis lipoidica affects females more often than males.

The pathogenesis of NL is not well understood but likely involves secondary microangiopathy because of glycoprotein deposition in vessel walls, leading to vascular thickening. Histopathology reveals palisading and necrobiotic granulomas comprising large confluent areas of necrobiosis throughout the dermis, giving a layered appearance.³

Clinically, NL presents with asymptomatic, well-circumscribed, violaceous papules and nodules that coalesce into plaques on the lower extremities, face, or trunk. The plaques have a central red-brown hue that progressively becomes more yellow and atrophic. The lesions can become eroded and ulcerated if left untreated.¹

Clinical diagnosis of NL can be challenging due to the similar clinical findings of other granulomatous lesions, such as granuloma annulare and cutaneous sarcoidosis. As reported by Pellicano and colleagues,⁴ dermoscopy has proved to be an excellent tool for differentiating these granulomatous skin lesions. Necrobiosis lipoidica demonstrates elongated serpentine telangiectases overlying a white structureless background, whereas granuloma annulare reveals orange-red structureless peripheral borders.⁵

Treatment of NL is difficult; patients often are refractory. Tight control of blood glucose alone has not been proven to cure NL. The mainstay of treatment is topical and intralesional corticosteroids at the active borders of the lesions. Tumor necrosis factor α inhibitors have shown some success, though recurrence has been reported.⁶ Other treatments, such as topical tretinoin and topical tacrolimus, may be of some benefit for atrophic NL lesions. Studies also have shown that skin grafting can be of surgical benefit in ulcerative NL with a low rate of recurrence.⁶ Control and management of DM plus lifestyle modifications may play a role in decreasing the severity of NL.⁷ Topical psoralen plus UVA light therapy and other experimental treatments, such as antiplatelet medications,⁸ also have been utilized.

The case of NL presented here was complicated by a superimposed suppurative infection consistent with PV, a rare chronic bacterial infection of the skin that presents with vegetative plaques. Pyoderma vegetans is most commonly observed in patients with underlying immunosuppression, likely secondary to DM in this case. Pyoderma vegetans is most often caused by S aureus and β-hemolytic streptococci. The clinical presentation of PV reveals verrucous vegetative plaques with pustules and abscesses. The borders of the lesions may be elevated and have a granulomatous appearance, thus complicating clinical diagnosis. There often is foul-smelling, purulent discharge within the plaques.⁹

Histopathology reveals pseudoepitheliomatous hyperplasia with abscesses and sinus tracts. An acute or chronic granulomatous inflammatory infiltrate may be observed. Basophilic fungus like granules are not seen within specimens of PV, which helps differentiate the disease from botryomycosis.¹⁰

There is no standardized treatment of PV; topical and systemic antibiotics are mainstays.¹⁰ One reported case of PV responded well to acitretin.⁹ Our patient responded well to 3 months of oral antibiotic therapy, followed by topical corticosteroids.

Case Report

A 26-year-old woman with a medical history of newly diagnosed diabetes mellitus (DM), obesity, and asthma was evaluated as a hospital consultation with a vegetative plaque on the left lateral ankle of 13 months’ duration. The lesion first appeared as a red scaly rash that became purulent. The lesion had been treated with multiple rounds of topical antibiotics, oral antibiotics, topical antifungals, and corticosteroids without resolution. The patient denied pain or any decrease in ankle mobility. Review of systems was otherwise negative.

On physical examination, 3 large, pink, scaly, crusted plaques with surrounding erythema were observed (Figure 1A). On palpation, purulent drainage with a foul odor was noted in the area underlying the lesion. Initial punch biopsy demonstrated epidermal hyperplasia with neutrophil-rich sinus tracts consistent with pyoderma vegetans (PV)(Figure 2A). Tissue culture was positive for Staphylococcus aureus and Streptococcus anginosus. Cultures for both fungi and acid-fast bacilli were negative for growth.

The patient was treated with mupirocin ointment 2% and 3 months of cephalexin 250 mg twice daily, which cleared the purulent crust; however, serous drainage, ulceration, and erythema persisted. The patient needed an extended course of antibiotics, which had not been previously administered to clear the purulence. During this treatment regimen, the patient’s DM remained uncontrolled.

A second deeper punch biopsy revealed a layered granulomatous infiltrate with sclerosis throughout the dermis most consistent with necrobiosis lipoidica (NL)(Figure 2B). Direct immunofluorescence biopsy was negative. Once the PV was clear, betamethasone dipropionate ointment 0.05% was initiated to address the residual lesions (Figure 1B).

Physical examination combined with histopathologic findings and staphylococcal- and streptococcal-positive tissue cultures supported a diagnosis of NL with superimposed PV.

Comment

Necrobiosis lipoidica is a chronic granulomatous disease characterized by collagen degeneration, granulomatous formation, and endothelial wall thickening.¹ The condition is most commonly seen in association with insulin-dependent DM, though it also has been described in other inflammatory conditions. A case of NL in monozygotic twins has been reported, suggesting a genetic component in nondiabetic patients with NL.² Necrobiosis lipoidica affects females more often than males.

The pathogenesis of NL is not well understood but likely involves secondary microangiopathy because of glycoprotein deposition in vessel walls, leading to vascular thickening. Histopathology reveals palisading and necrobiotic granulomas comprising large confluent areas of necrobiosis throughout the dermis, giving a layered appearance.³

Clinically, NL presents with asymptomatic, well-circumscribed, violaceous papules and nodules that coalesce into plaques on the lower extremities, face, or trunk. The plaques have a central red-brown hue that progressively becomes more yellow and atrophic. The lesions can become eroded and ulcerated if left untreated.¹

Clinical diagnosis of NL can be challenging due to the similar clinical findings of other granulomatous lesions, such as granuloma annulare and cutaneous sarcoidosis. As reported by Pellicano and colleagues,⁴ dermoscopy has proved to be an excellent tool for differentiating these granulomatous skin lesions. Necrobiosis lipoidica demonstrates elongated serpentine telangiectases overlying a white structureless background, whereas granuloma annulare reveals orange-red structureless peripheral borders.⁵

Treatment of NL is difficult; patients often are refractory. Tight control of blood glucose alone has not been proven to cure NL. The mainstay of treatment is topical and intralesional corticosteroids at the active borders of the lesions. Tumor necrosis factor α inhibitors have shown some success, though recurrence has been reported.⁶ Other treatments, such as topical tretinoin and topical tacrolimus, may be of some benefit for atrophic NL lesions. Studies also have shown that skin grafting can be of surgical benefit in ulcerative NL with a low rate of recurrence.⁶ Control and management of DM plus lifestyle modifications may play a role in decreasing the severity of NL.⁷ Topical psoralen plus UVA light therapy and other experimental treatments, such as antiplatelet medications,⁸ also have been utilized.

The case of NL presented here was complicated by a superimposed suppurative infection consistent with PV, a rare chronic bacterial infection of the skin that presents with vegetative plaques. Pyoderma vegetans is most commonly observed in patients with underlying immunosuppression, likely secondary to DM in this case. Pyoderma vegetans is most often caused by S aureus and β-hemolytic streptococci. The clinical presentation of PV reveals verrucous vegetative plaques with pustules and abscesses. The borders of the lesions may be elevated and have a granulomatous appearance, thus complicating clinical diagnosis. There often is foul-smelling, purulent discharge within the plaques.⁹

Histopathology reveals pseudoepitheliomatous hyperplasia with abscesses and sinus tracts. An acute or chronic granulomatous inflammatory infiltrate may be observed. Basophilic fungus like granules are not seen within specimens of PV, which helps differentiate the disease from botryomycosis.¹⁰

There is no standardized treatment of PV; topical and systemic antibiotics are mainstays.¹⁰ One reported case of PV responded well to acitretin.⁹ Our patient responded well to 3 months of oral antibiotic therapy, followed by topical corticosteroids.

Idiopathic granulomatous mastitis (IGM) is rare during pregnancy; it typically is seen in women of childbearing potential from 6 months to 6 years postpartum.¹ Because of a temporal association with breastfeeding, it is believed that hyperprolactinemia² or an immune response to local lobular secretions might play a role in pathogenesis. Early misdiagnosis as bacterial mastitis is common, prompting multiple antibiotic regimens. When antibiotics fail, patients are worked up for inflammatory breast cancer, given the nonhealing breast nodules. Mammography, ultrasonography, and fine-needle aspiration often are unable to rule out carcinoma, warranting excisional biopsies of nodules. The patient is then referred to rheumatology for potential sarcoidosis or to dermatology for IGM. In either case, the workup should be similar, but additional history focused on behavior and medications is essential in suspected IGM, given the association with hyperprolactinemia.

Because IGM is rare, there are no randomized, placebo-controlled trials of treatment efficacy. In many cases, patients undergo complete mastectomy, which is curative but may be psychologically and physically impactful in young women. In some cases, high-dose corticosteroids have been successful; however, because the IGM process can last longer than 2 years, patients treated in this manner are exposed to steroid morbidities.¹

We report 3 cases of IGM that add to the literature on possible contributing factors, clinical presentations, and treatments for this disease. We also demonstrate that appropriate trigger identification and steroid-sparing agents, specifically methotrexate, can be breast-saving as they can alleviate this debilitating condition, obviating the need for radical surgical intervention.

CASE REPORTS 

Patient 1

A 40-year-old woman with a 4-year history of breastfeeding noted a grape-sized nodule on the left breast that grew to the size of a grapefruit after 2 weeks. Ulceration and drainage periodically occurred, forming pink plaques along the lateral aspects of the breast after healing. Her primary care provider suspected infectious mastitis; she was given an oral antibiotic (cephalexin) and intravenous antibiotics without improvement.

Imaging
Subsequent magnetic resonance imaging revealed a large, irregular, enhancing mass within the outer left breast (6.5 cm at greatest dimension) with additional surrounding amorphous enhancement highly suspicious for malignancy. There also were multiple prominent left axillary lymph nodes, with the largest demonstrating a cortical thickness of 8 mm.

Biopsy
Core breast biopsy showed benign tissue with fat necrosis. Fine-needle aspiration revealed few benign ductal cells and rare histiocytes; because these findings were nondiagnostic and cancer was still a consideration, the patient underwent excisional biopsy.

Histologic sections of breast tissue showed extensive lobulocentric inflammation comprising histiocytes and lymphocytes, with neutrophils admixed and forming microabscesses (Figure 1A). Multinucleated giant cells and single-cell necrosis were seen, but true caseous necrosis was absent (Figure 1B). Duct spaces often contained inflammatory cells or secretions. Special stains for fungal and acid-fast bacterial microorganisms were negative.

Granulomatous lobular mastitis was diagnosed, and the patient was referred to dermatology. On presentation to dermatology, the left breast showed a 6-cm area of firm induration and overlying peau d’orange change to the epidermis (Figure 2A). Based on pathologic analysis, she was worked up for a possible granulomatous etiology. Negative purified protein derivative (tuberculin)(PPD) and a normal chest radiograph ruled out tuberculosis. Normal chest radiography, serum Ca²⁺ and angiotensin-converting enzyme (ACE) levels, and ophthalmology examination ruled out sarcoidosis.

The patient reported she continued breastfeeding her 4-year-old son. Additionally, she had been started on trazadone and buspirone for alcohol abuse recovery, then switched to and maintained on fluoxetine 1 year before developing these symptoms.

Buspirone, fluoxetine, and prolonged breastfeeding all contribute to hyperprolactinemia, a possible trigger of IGM. The patient was therefore advised to stop breastfeeding and to be switched from fluoxetine to a medication that would not increase the prolactin level. She did not require methotrexate treatment because her condition resolved rapidly after breastfeeding and fluoxetine were discontinued (Figure 2B).

Patient 2 

A 40-year-old woman with no history of breastfeeding who gave birth 4.5 years prior presented to her primary care provider with a painful breast lump and rash on the right breast of 2 months’ duration. Infectious mastitis was suspected; she was given cephalexin and clindamycin without improvement of symptoms.

Imaging
Mammography and ultrasonography were nondiagnostic.

Biopsy
Breast biopsy showed tissue with large expanses of histiocytes, neutrophils, lymphocytes, plasma cells, and multinucleated giant cells (Figure 3A). Many discrete granulomas were seen against this mixed inflammatory background, associated with focal fat necrosis (Figure 3B). Special stains were negative for microorganisms. Histologic findings were consistent with granulomatous mastitis.

On presentation to dermatology, the patient was worked up for a possible granulomatous etiology, which included a negative PPD, as well as a normal chest radiograph, serum Ca²⁺ and ACE levels, and ophthalmology examination. Review of symptoms (ROS),medical history, and medication review were unremarkable.

By exclusion, the patient was given a diagnosis of IGM and started on methotrexate (15 mg weekly) with folic acid (1 mg daily). The condition of the right breast improved within 4 weeks of starting methotrexate; however, methotrexate was increased to 30 mg weekly because of occasional flares. The patient remained on methotrexate without further IGM flares for 8 months compared to prior unremitting pain and drainage. She was then tapered from methotrexate over 6 weeks without additional flares.

A 27-year-old woman who gave birth 2 years prior and discontinued breastfeeding 6 weeks after delivery noted bilateral breast rashes for several months. The lesions were growing in size, tender, and draining. Her primary care provider suspected infectious mastitis and prescribed antibiotics, which were ineffective.

Biopsy
Breast core biopsy showed histologic findings similar to patients 1 and 2, including lobulocentric mixed inflammation, neutrophilic microabscesses, and scattered discrete granulomas. Microorganisms were not found using special stains. Breast cancer was ruled out, and granulomatous mastitis was diagnosed.

Referral to Dermatology
Two years earlier, the patient tested positive for latent tuberculosis and was prescribed a 9-month regimen of isoniazid. At the current presentation, she did not have symptoms of active tuberculosis on ROS (ie, no cough, hemoptysis, weight loss, night sweats); a chest radiograph was normal. Additionally, serum Ca²⁺ and ACE levels as well as an ophthalmology examination were normal, and she was not taking any medications known to increase the prolactin level.

The patient was started on methotrexate (12.5 mg weekly) and folic acid (1 mg daily). She had 1 IGM flare and was given a tapering regimen of prednisone. She received methotrexate for 14 months, tapered during the final 3 months. She has been off methotrexate for 3 years without IGM flares and appears to be in complete remission.

COMMENT

We report 3 cases of IGM, which contribute to the literature on possible presentations, causes, and conservative treatment of this rare connective-tissue disorder.

Differential Diagnosis

The time between recognition of symptoms and diagnosis and treatment of IGM often is prolonged because IGM can present similarly to other disorders, such as infection, breast cancer, tuberculosis, and sarcoidosis. Idiopathic granulomatous mastitis is a diagnosis of exclusion, made after obtaining evidence of granulomatous inflammation on breast biopsy and ruling out other granulomatous disorders, such as tuberculosis and sarcoidosis (Table 1).^3,4

Tuberculosis
A full ROS and a PPD test or T-SPOT.TB test can be helpful in ruling out tuberculosis; because anergy occurs in some patients, tuberculosis should be evaluated in the context of known immunosuppression or human immunodeficiency virus status, or in the case of miliary tuberculosis.

Chest radiography findings classically showing upper lobe infiltrates with cavities in active tuberculosis also should be sought.³ Ziehl-Neelsen staining of 2 sputum specimens, assessed by conventional light microscopy at the time of tissue biopsy has 64% sensitivity and 98% specificity for detecting Mycobacterium tuberculosis; auramine O staining, examined with light-emitting diode fluorescence microscopy, has 73% sensitivity and 93% specificity.⁵

Sarcoidosis
Because more than 90% of sarcoid patients have lung disease, a chest radiograph is used to screen for hilar lymphadenopathy.³ An elevated serum ACE level also can be helpful in diagnosis, but patients do not always have increased ACE, which can occur in other diseases, such as hyperthyroidism and miliary tuberculosis. Sarcoid granulomas can increase active vitamin D production, which in turn increases serum Ca²⁺ in 10% of sarcoid patients. Last, an ophthalmology evaluation should be obtained to rule out anterior or posterior uveitis that can occur in sarcoidosis and initially remain asymptomatic.³ Once these other causes of granulomatous inflammation have been ruled out, a diagnosis of IGM can be made.

Prolactinoma
Prolactinoma is an important cause of hyperprolactinemia that can be screened for based on ROS and the serum prolactin level. Prolactinoma can cause oligomenorrhea or amenorrhea and galactorrhea in 90% and 80% of premenopausal women, respectively, as well as erectile dysfunction and decreased libido in men. Infertility, headache, and visual impairment may be experienced in both sexes.⁴

A normal prolactin level is less than 25 μg/L; more than 25 μg/L but less than 100 μg/L usually is due to certain drugs (eTable),^6-11 estrogen, or idiopathic reasons; and more than 150 μg/L usually is due to prolactinoma.⁵ In many cases, removal of hyperprolactinemia-precipitating factors can resolve disease, as in patient 1. If symptoms continue or precipitating factors are absent, IGM symptom-based treatment should be administered.

Course and Management

Idiopathic granulomatous mastitis is self-limited and usually resolves within 2 years. Therefore, the goal of treatment is to suppress associated pain and drainage until the active inflammatory phase of IGM self-resolves. An established protocol for treating IGM does not exist, but common treatments include corticosteroids, methotrexate, and limited or wide surgical excision (Table 2).^12-16 Before beginning any of these treatments, IGM triggers, such as breastfeeding and drugs that induce hyperprolactinemia, should be removed.

It is important to consider which treatment option is best for limiting disease recurrence and adverse effects (AEs). Keep in mind that the available data are limited, as there are no randomized controlled trials looking at these treatments. Nevertheless, we recommend methotrexate as first line because it resolves granulomatous inflammation symptoms without invasive surgery, while limiting corticosteroid AEs.¹²

With or without concurrent use of corticosteroids, surgical excision typically is the mainstay of treatment. However, surgical excision of IGM lesions can be complicated by abscess formation, fistula, and chronic pyogenic secretions, in addition to a 5% to 50% rate of recurrence of disease.^12-14 Limited excision often is insufficient; therefore, wide local excision, in which negative margins around granulomatous inflammation are obtained, is the surgical modality of choice.¹⁴ Wide local excision can be disfiguring to the breast in young women affected by IGM, making it an undesirable treatment option.

Corticosteroids often have been used to treat IGM, but their efficacy is variable, symptoms can recur upon drug removal, and remarkable AEs can result from long-term use.¹² Additionally, corticosteroid therapy often is used in combination with excision, making it difficult to determine the extent to which corticosteroids or excision are more beneficial. In a prospective observational study, corticosteroid therapy alone resolved 80% of IGM symptoms after 159 days on average. After complete symptom resolution, 23% of patients had disease recurrence.⁹ Observed AEs included gastritis, weight gain, osteoporosis, glucose intolerance, and Cushing syndrome.^12,15

Methotrexate for IGM has not been reviewed in a randomized controlled trial; case reports have shown 83% symptom resolution, with 17% recurrence and limited long-term AEs.¹² Because the active phase of IGM can persist for 2 years, immunosuppressive therapy with limited AEs is necessary. Many AEs can occur when high-dose methotrexate is given for cancer treatment. Low-dose methotrexate has been extensively studied in long-term treatment of rheumatoid arthritis. Adverse effects may include gastrointestinal tract upset and hepatic dysfunction, which are limited when given with folic acid.

Regardless of folic acid cotreatment, stomatitis may occur. Women should use an effective method of birth control because severe birth defects may occur on even low-dose methotrexate.¹⁶

Compared to corticosteroid or surgical treatment, we recommend low-dose methotrexate therapy based on its high efficacy with limited AEs. An occasional mild flare of IGM symptoms with methotrexate is not unusual. If it occurs, corticosteroids can be added and tapered for as long as 2 weeks to speed up resolution of flares while reducing long-term AEs of corticosteroids.

Surgical excision can be performed in cases refractory to all systemic therapies.

CONCLUSION

Idiopathic granulomatous mastitis is a rare granulomatous breast disorder that can have a prolonged time to diagnosis, delaying proper treatment. Many cases self-resolve, but more severe cases can persist for a long period before adequate symptomatic treatment is achieved by methotrexate, corticosteroids, or surgical excision. Before using these therapies, it is important to identify and remove contributing factors, such as long-term breastfeeding and drugs that induce hyperprolactinemia. Improving the rate of IGM diagnosis and treatment would greatly benefit these patients. We report 1 case in which removal of possible precipitating IGM factors led to symptom resolution and 2 cases in which methotrexate was an effective IGM treatment that limited the need for invasive procedures and corticosteroid AEs.

Idiopathic granulomatous mastitis (IGM) is rare during pregnancy; it typically is seen in women of childbearing potential from 6 months to 6 years postpartum.¹ Because of a temporal association with breastfeeding, it is believed that hyperprolactinemia² or an immune response to local lobular secretions might play a role in pathogenesis. Early misdiagnosis as bacterial mastitis is common, prompting multiple antibiotic regimens. When antibiotics fail, patients are worked up for inflammatory breast cancer, given the nonhealing breast nodules. Mammography, ultrasonography, and fine-needle aspiration often are unable to rule out carcinoma, warranting excisional biopsies of nodules. The patient is then referred to rheumatology for potential sarcoidosis or to dermatology for IGM. In either case, the workup should be similar, but additional history focused on behavior and medications is essential in suspected IGM, given the association with hyperprolactinemia.

Because IGM is rare, there are no randomized, placebo-controlled trials of treatment efficacy. In many cases, patients undergo complete mastectomy, which is curative but may be psychologically and physically impactful in young women. In some cases, high-dose corticosteroids have been successful; however, because the IGM process can last longer than 2 years, patients treated in this manner are exposed to steroid morbidities.¹

We report 3 cases of IGM that add to the literature on possible contributing factors, clinical presentations, and treatments for this disease. We also demonstrate that appropriate trigger identification and steroid-sparing agents, specifically methotrexate, can be breast-saving as they can alleviate this debilitating condition, obviating the need for radical surgical intervention.

CASE REPORTS 

Patient 1

A 40-year-old woman with a 4-year history of breastfeeding noted a grape-sized nodule on the left breast that grew to the size of a grapefruit after 2 weeks. Ulceration and drainage periodically occurred, forming pink plaques along the lateral aspects of the breast after healing. Her primary care provider suspected infectious mastitis; she was given an oral antibiotic (cephalexin) and intravenous antibiotics without improvement.

Imaging
Subsequent magnetic resonance imaging revealed a large, irregular, enhancing mass within the outer left breast (6.5 cm at greatest dimension) with additional surrounding amorphous enhancement highly suspicious for malignancy. There also were multiple prominent left axillary lymph nodes, with the largest demonstrating a cortical thickness of 8 mm.

Biopsy
Core breast biopsy showed benign tissue with fat necrosis. Fine-needle aspiration revealed few benign ductal cells and rare histiocytes; because these findings were nondiagnostic and cancer was still a consideration, the patient underwent excisional biopsy.

Histologic sections of breast tissue showed extensive lobulocentric inflammation comprising histiocytes and lymphocytes, with neutrophils admixed and forming microabscesses (Figure 1A). Multinucleated giant cells and single-cell necrosis were seen, but true caseous necrosis was absent (Figure 1B). Duct spaces often contained inflammatory cells or secretions. Special stains for fungal and acid-fast bacterial microorganisms were negative.

Granulomatous lobular mastitis was diagnosed, and the patient was referred to dermatology. On presentation to dermatology, the left breast showed a 6-cm area of firm induration and overlying peau d’orange change to the epidermis (Figure 2A). Based on pathologic analysis, she was worked up for a possible granulomatous etiology. Negative purified protein derivative (tuberculin)(PPD) and a normal chest radiograph ruled out tuberculosis. Normal chest radiography, serum Ca²⁺ and angiotensin-converting enzyme (ACE) levels, and ophthalmology examination ruled out sarcoidosis.

The patient reported she continued breastfeeding her 4-year-old son. Additionally, she had been started on trazadone and buspirone for alcohol abuse recovery, then switched to and maintained on fluoxetine 1 year before developing these symptoms.

Buspirone, fluoxetine, and prolonged breastfeeding all contribute to hyperprolactinemia, a possible trigger of IGM. The patient was therefore advised to stop breastfeeding and to be switched from fluoxetine to a medication that would not increase the prolactin level. She did not require methotrexate treatment because her condition resolved rapidly after breastfeeding and fluoxetine were discontinued (Figure 2B).

Patient 2 

A 40-year-old woman with no history of breastfeeding who gave birth 4.5 years prior presented to her primary care provider with a painful breast lump and rash on the right breast of 2 months’ duration. Infectious mastitis was suspected; she was given cephalexin and clindamycin without improvement of symptoms.

Imaging
Mammography and ultrasonography were nondiagnostic.

Biopsy
Breast biopsy showed tissue with large expanses of histiocytes, neutrophils, lymphocytes, plasma cells, and multinucleated giant cells (Figure 3A). Many discrete granulomas were seen against this mixed inflammatory background, associated with focal fat necrosis (Figure 3B). Special stains were negative for microorganisms. Histologic findings were consistent with granulomatous mastitis.

On presentation to dermatology, the patient was worked up for a possible granulomatous etiology, which included a negative PPD, as well as a normal chest radiograph, serum Ca²⁺ and ACE levels, and ophthalmology examination. Review of symptoms (ROS),medical history, and medication review were unremarkable.

By exclusion, the patient was given a diagnosis of IGM and started on methotrexate (15 mg weekly) with folic acid (1 mg daily). The condition of the right breast improved within 4 weeks of starting methotrexate; however, methotrexate was increased to 30 mg weekly because of occasional flares. The patient remained on methotrexate without further IGM flares for 8 months compared to prior unremitting pain and drainage. She was then tapered from methotrexate over 6 weeks without additional flares.

A 27-year-old woman who gave birth 2 years prior and discontinued breastfeeding 6 weeks after delivery noted bilateral breast rashes for several months. The lesions were growing in size, tender, and draining. Her primary care provider suspected infectious mastitis and prescribed antibiotics, which were ineffective.

Biopsy
Breast core biopsy showed histologic findings similar to patients 1 and 2, including lobulocentric mixed inflammation, neutrophilic microabscesses, and scattered discrete granulomas. Microorganisms were not found using special stains. Breast cancer was ruled out, and granulomatous mastitis was diagnosed.

Referral to Dermatology
Two years earlier, the patient tested positive for latent tuberculosis and was prescribed a 9-month regimen of isoniazid. At the current presentation, she did not have symptoms of active tuberculosis on ROS (ie, no cough, hemoptysis, weight loss, night sweats); a chest radiograph was normal. Additionally, serum Ca²⁺ and ACE levels as well as an ophthalmology examination were normal, and she was not taking any medications known to increase the prolactin level.

The patient was started on methotrexate (12.5 mg weekly) and folic acid (1 mg daily). She had 1 IGM flare and was given a tapering regimen of prednisone. She received methotrexate for 14 months, tapered during the final 3 months. She has been off methotrexate for 3 years without IGM flares and appears to be in complete remission.

COMMENT

We report 3 cases of IGM, which contribute to the literature on possible presentations, causes, and conservative treatment of this rare connective-tissue disorder.

Differential Diagnosis

The time between recognition of symptoms and diagnosis and treatment of IGM often is prolonged because IGM can present similarly to other disorders, such as infection, breast cancer, tuberculosis, and sarcoidosis. Idiopathic granulomatous mastitis is a diagnosis of exclusion, made after obtaining evidence of granulomatous inflammation on breast biopsy and ruling out other granulomatous disorders, such as tuberculosis and sarcoidosis (Table 1).^3,4

Tuberculosis
A full ROS and a PPD test or T-SPOT.TB test can be helpful in ruling out tuberculosis; because anergy occurs in some patients, tuberculosis should be evaluated in the context of known immunosuppression or human immunodeficiency virus status, or in the case of miliary tuberculosis.

Chest radiography findings classically showing upper lobe infiltrates with cavities in active tuberculosis also should be sought.³ Ziehl-Neelsen staining of 2 sputum specimens, assessed by conventional light microscopy at the time of tissue biopsy has 64% sensitivity and 98% specificity for detecting Mycobacterium tuberculosis; auramine O staining, examined with light-emitting diode fluorescence microscopy, has 73% sensitivity and 93% specificity.⁵

Sarcoidosis
Because more than 90% of sarcoid patients have lung disease, a chest radiograph is used to screen for hilar lymphadenopathy.³ An elevated serum ACE level also can be helpful in diagnosis, but patients do not always have increased ACE, which can occur in other diseases, such as hyperthyroidism and miliary tuberculosis. Sarcoid granulomas can increase active vitamin D production, which in turn increases serum Ca²⁺ in 10% of sarcoid patients. Last, an ophthalmology evaluation should be obtained to rule out anterior or posterior uveitis that can occur in sarcoidosis and initially remain asymptomatic.³ Once these other causes of granulomatous inflammation have been ruled out, a diagnosis of IGM can be made.

Prolactinoma
Prolactinoma is an important cause of hyperprolactinemia that can be screened for based on ROS and the serum prolactin level. Prolactinoma can cause oligomenorrhea or amenorrhea and galactorrhea in 90% and 80% of premenopausal women, respectively, as well as erectile dysfunction and decreased libido in men. Infertility, headache, and visual impairment may be experienced in both sexes.⁴

A normal prolactin level is less than 25 μg/L; more than 25 μg/L but less than 100 μg/L usually is due to certain drugs (eTable),^6-11 estrogen, or idiopathic reasons; and more than 150 μg/L usually is due to prolactinoma.⁵ In many cases, removal of hyperprolactinemia-precipitating factors can resolve disease, as in patient 1. If symptoms continue or precipitating factors are absent, IGM symptom-based treatment should be administered.

Course and Management

Idiopathic granulomatous mastitis is self-limited and usually resolves within 2 years. Therefore, the goal of treatment is to suppress associated pain and drainage until the active inflammatory phase of IGM self-resolves. An established protocol for treating IGM does not exist, but common treatments include corticosteroids, methotrexate, and limited or wide surgical excision (Table 2).^12-16 Before beginning any of these treatments, IGM triggers, such as breastfeeding and drugs that induce hyperprolactinemia, should be removed.

It is important to consider which treatment option is best for limiting disease recurrence and adverse effects (AEs). Keep in mind that the available data are limited, as there are no randomized controlled trials looking at these treatments. Nevertheless, we recommend methotrexate as first line because it resolves granulomatous inflammation symptoms without invasive surgery, while limiting corticosteroid AEs.¹²

With or without concurrent use of corticosteroids, surgical excision typically is the mainstay of treatment. However, surgical excision of IGM lesions can be complicated by abscess formation, fistula, and chronic pyogenic secretions, in addition to a 5% to 50% rate of recurrence of disease.^12-14 Limited excision often is insufficient; therefore, wide local excision, in which negative margins around granulomatous inflammation are obtained, is the surgical modality of choice.¹⁴ Wide local excision can be disfiguring to the breast in young women affected by IGM, making it an undesirable treatment option.

Corticosteroids often have been used to treat IGM, but their efficacy is variable, symptoms can recur upon drug removal, and remarkable AEs can result from long-term use.¹² Additionally, corticosteroid therapy often is used in combination with excision, making it difficult to determine the extent to which corticosteroids or excision are more beneficial. In a prospective observational study, corticosteroid therapy alone resolved 80% of IGM symptoms after 159 days on average. After complete symptom resolution, 23% of patients had disease recurrence.⁹ Observed AEs included gastritis, weight gain, osteoporosis, glucose intolerance, and Cushing syndrome.^12,15

Methotrexate for IGM has not been reviewed in a randomized controlled trial; case reports have shown 83% symptom resolution, with 17% recurrence and limited long-term AEs.¹² Because the active phase of IGM can persist for 2 years, immunosuppressive therapy with limited AEs is necessary. Many AEs can occur when high-dose methotrexate is given for cancer treatment. Low-dose methotrexate has been extensively studied in long-term treatment of rheumatoid arthritis. Adverse effects may include gastrointestinal tract upset and hepatic dysfunction, which are limited when given with folic acid.

Regardless of folic acid cotreatment, stomatitis may occur. Women should use an effective method of birth control because severe birth defects may occur on even low-dose methotrexate.¹⁶

Compared to corticosteroid or surgical treatment, we recommend low-dose methotrexate therapy based on its high efficacy with limited AEs. An occasional mild flare of IGM symptoms with methotrexate is not unusual. If it occurs, corticosteroids can be added and tapered for as long as 2 weeks to speed up resolution of flares while reducing long-term AEs of corticosteroids.

Surgical excision can be performed in cases refractory to all systemic therapies.

CONCLUSION

Idiopathic granulomatous mastitis is a rare granulomatous breast disorder that can have a prolonged time to diagnosis, delaying proper treatment. Many cases self-resolve, but more severe cases can persist for a long period before adequate symptomatic treatment is achieved by methotrexate, corticosteroids, or surgical excision. Before using these therapies, it is important to identify and remove contributing factors, such as long-term breastfeeding and drugs that induce hyperprolactinemia. Improving the rate of IGM diagnosis and treatment would greatly benefit these patients. We report 1 case in which removal of possible precipitating IGM factors led to symptom resolution and 2 cases in which methotrexate was an effective IGM treatment that limited the need for invasive procedures and corticosteroid AEs.

Idiopathic granulomatous mastitis (IGM) is rare during pregnancy; it typically is seen in women of childbearing potential from 6 months to 6 years postpartum.¹ Because of a temporal association with breastfeeding, it is believed that hyperprolactinemia² or an immune response to local lobular secretions might play a role in pathogenesis. Early misdiagnosis as bacterial mastitis is common, prompting multiple antibiotic regimens. When antibiotics fail, patients are worked up for inflammatory breast cancer, given the nonhealing breast nodules. Mammography, ultrasonography, and fine-needle aspiration often are unable to rule out carcinoma, warranting excisional biopsies of nodules. The patient is then referred to rheumatology for potential sarcoidosis or to dermatology for IGM. In either case, the workup should be similar, but additional history focused on behavior and medications is essential in suspected IGM, given the association with hyperprolactinemia.

Because IGM is rare, there are no randomized, placebo-controlled trials of treatment efficacy. In many cases, patients undergo complete mastectomy, which is curative but may be psychologically and physically impactful in young women. In some cases, high-dose corticosteroids have been successful; however, because the IGM process can last longer than 2 years, patients treated in this manner are exposed to steroid morbidities.¹

We report 3 cases of IGM that add to the literature on possible contributing factors, clinical presentations, and treatments for this disease. We also demonstrate that appropriate trigger identification and steroid-sparing agents, specifically methotrexate, can be breast-saving as they can alleviate this debilitating condition, obviating the need for radical surgical intervention.

CASE REPORTS 

Patient 1

A 40-year-old woman with a 4-year history of breastfeeding noted a grape-sized nodule on the left breast that grew to the size of a grapefruit after 2 weeks. Ulceration and drainage periodically occurred, forming pink plaques along the lateral aspects of the breast after healing. Her primary care provider suspected infectious mastitis; she was given an oral antibiotic (cephalexin) and intravenous antibiotics without improvement.

Imaging
Subsequent magnetic resonance imaging revealed a large, irregular, enhancing mass within the outer left breast (6.5 cm at greatest dimension) with additional surrounding amorphous enhancement highly suspicious for malignancy. There also were multiple prominent left axillary lymph nodes, with the largest demonstrating a cortical thickness of 8 mm.

Biopsy
Core breast biopsy showed benign tissue with fat necrosis. Fine-needle aspiration revealed few benign ductal cells and rare histiocytes; because these findings were nondiagnostic and cancer was still a consideration, the patient underwent excisional biopsy.

Histologic sections of breast tissue showed extensive lobulocentric inflammation comprising histiocytes and lymphocytes, with neutrophils admixed and forming microabscesses (Figure 1A). Multinucleated giant cells and single-cell necrosis were seen, but true caseous necrosis was absent (Figure 1B). Duct spaces often contained inflammatory cells or secretions. Special stains for fungal and acid-fast bacterial microorganisms were negative.

Granulomatous lobular mastitis was diagnosed, and the patient was referred to dermatology. On presentation to dermatology, the left breast showed a 6-cm area of firm induration and overlying peau d’orange change to the epidermis (Figure 2A). Based on pathologic analysis, she was worked up for a possible granulomatous etiology. Negative purified protein derivative (tuberculin)(PPD) and a normal chest radiograph ruled out tuberculosis. Normal chest radiography, serum Ca²⁺ and angiotensin-converting enzyme (ACE) levels, and ophthalmology examination ruled out sarcoidosis.

The patient reported she continued breastfeeding her 4-year-old son. Additionally, she had been started on trazadone and buspirone for alcohol abuse recovery, then switched to and maintained on fluoxetine 1 year before developing these symptoms.

Buspirone, fluoxetine, and prolonged breastfeeding all contribute to hyperprolactinemia, a possible trigger of IGM. The patient was therefore advised to stop breastfeeding and to be switched from fluoxetine to a medication that would not increase the prolactin level. She did not require methotrexate treatment because her condition resolved rapidly after breastfeeding and fluoxetine were discontinued (Figure 2B).

Patient 2 

A 40-year-old woman with no history of breastfeeding who gave birth 4.5 years prior presented to her primary care provider with a painful breast lump and rash on the right breast of 2 months’ duration. Infectious mastitis was suspected; she was given cephalexin and clindamycin without improvement of symptoms.

Imaging
Mammography and ultrasonography were nondiagnostic.

Biopsy
Breast biopsy showed tissue with large expanses of histiocytes, neutrophils, lymphocytes, plasma cells, and multinucleated giant cells (Figure 3A). Many discrete granulomas were seen against this mixed inflammatory background, associated with focal fat necrosis (Figure 3B). Special stains were negative for microorganisms. Histologic findings were consistent with granulomatous mastitis.

On presentation to dermatology, the patient was worked up for a possible granulomatous etiology, which included a negative PPD, as well as a normal chest radiograph, serum Ca²⁺ and ACE levels, and ophthalmology examination. Review of symptoms (ROS),medical history, and medication review were unremarkable.

By exclusion, the patient was given a diagnosis of IGM and started on methotrexate (15 mg weekly) with folic acid (1 mg daily). The condition of the right breast improved within 4 weeks of starting methotrexate; however, methotrexate was increased to 30 mg weekly because of occasional flares. The patient remained on methotrexate without further IGM flares for 8 months compared to prior unremitting pain and drainage. She was then tapered from methotrexate over 6 weeks without additional flares.

A 27-year-old woman who gave birth 2 years prior and discontinued breastfeeding 6 weeks after delivery noted bilateral breast rashes for several months. The lesions were growing in size, tender, and draining. Her primary care provider suspected infectious mastitis and prescribed antibiotics, which were ineffective.

Biopsy
Breast core biopsy showed histologic findings similar to patients 1 and 2, including lobulocentric mixed inflammation, neutrophilic microabscesses, and scattered discrete granulomas. Microorganisms were not found using special stains. Breast cancer was ruled out, and granulomatous mastitis was diagnosed.

Referral to Dermatology
Two years earlier, the patient tested positive for latent tuberculosis and was prescribed a 9-month regimen of isoniazid. At the current presentation, she did not have symptoms of active tuberculosis on ROS (ie, no cough, hemoptysis, weight loss, night sweats); a chest radiograph was normal. Additionally, serum Ca²⁺ and ACE levels as well as an ophthalmology examination were normal, and she was not taking any medications known to increase the prolactin level.

The patient was started on methotrexate (12.5 mg weekly) and folic acid (1 mg daily). She had 1 IGM flare and was given a tapering regimen of prednisone. She received methotrexate for 14 months, tapered during the final 3 months. She has been off methotrexate for 3 years without IGM flares and appears to be in complete remission.

COMMENT

We report 3 cases of IGM, which contribute to the literature on possible presentations, causes, and conservative treatment of this rare connective-tissue disorder.

Differential Diagnosis

The time between recognition of symptoms and diagnosis and treatment of IGM often is prolonged because IGM can present similarly to other disorders, such as infection, breast cancer, tuberculosis, and sarcoidosis. Idiopathic granulomatous mastitis is a diagnosis of exclusion, made after obtaining evidence of granulomatous inflammation on breast biopsy and ruling out other granulomatous disorders, such as tuberculosis and sarcoidosis (Table 1).^3,4

Tuberculosis
A full ROS and a PPD test or T-SPOT.TB test can be helpful in ruling out tuberculosis; because anergy occurs in some patients, tuberculosis should be evaluated in the context of known immunosuppression or human immunodeficiency virus status, or in the case of miliary tuberculosis.

Chest radiography findings classically showing upper lobe infiltrates with cavities in active tuberculosis also should be sought.³ Ziehl-Neelsen staining of 2 sputum specimens, assessed by conventional light microscopy at the time of tissue biopsy has 64% sensitivity and 98% specificity for detecting Mycobacterium tuberculosis; auramine O staining, examined with light-emitting diode fluorescence microscopy, has 73% sensitivity and 93% specificity.⁵

Sarcoidosis
Because more than 90% of sarcoid patients have lung disease, a chest radiograph is used to screen for hilar lymphadenopathy.³ An elevated serum ACE level also can be helpful in diagnosis, but patients do not always have increased ACE, which can occur in other diseases, such as hyperthyroidism and miliary tuberculosis. Sarcoid granulomas can increase active vitamin D production, which in turn increases serum Ca²⁺ in 10% of sarcoid patients. Last, an ophthalmology evaluation should be obtained to rule out anterior or posterior uveitis that can occur in sarcoidosis and initially remain asymptomatic.³ Once these other causes of granulomatous inflammation have been ruled out, a diagnosis of IGM can be made.

Prolactinoma
Prolactinoma is an important cause of hyperprolactinemia that can be screened for based on ROS and the serum prolactin level. Prolactinoma can cause oligomenorrhea or amenorrhea and galactorrhea in 90% and 80% of premenopausal women, respectively, as well as erectile dysfunction and decreased libido in men. Infertility, headache, and visual impairment may be experienced in both sexes.⁴

A normal prolactin level is less than 25 μg/L; more than 25 μg/L but less than 100 μg/L usually is due to certain drugs (eTable),^6-11 estrogen, or idiopathic reasons; and more than 150 μg/L usually is due to prolactinoma.⁵ In many cases, removal of hyperprolactinemia-precipitating factors can resolve disease, as in patient 1. If symptoms continue or precipitating factors are absent, IGM symptom-based treatment should be administered.

Course and Management

Idiopathic granulomatous mastitis is self-limited and usually resolves within 2 years. Therefore, the goal of treatment is to suppress associated pain and drainage until the active inflammatory phase of IGM self-resolves. An established protocol for treating IGM does not exist, but common treatments include corticosteroids, methotrexate, and limited or wide surgical excision (Table 2).^12-16 Before beginning any of these treatments, IGM triggers, such as breastfeeding and drugs that induce hyperprolactinemia, should be removed.

It is important to consider which treatment option is best for limiting disease recurrence and adverse effects (AEs). Keep in mind that the available data are limited, as there are no randomized controlled trials looking at these treatments. Nevertheless, we recommend methotrexate as first line because it resolves granulomatous inflammation symptoms without invasive surgery, while limiting corticosteroid AEs.¹²

With or without concurrent use of corticosteroids, surgical excision typically is the mainstay of treatment. However, surgical excision of IGM lesions can be complicated by abscess formation, fistula, and chronic pyogenic secretions, in addition to a 5% to 50% rate of recurrence of disease.^12-14 Limited excision often is insufficient; therefore, wide local excision, in which negative margins around granulomatous inflammation are obtained, is the surgical modality of choice.¹⁴ Wide local excision can be disfiguring to the breast in young women affected by IGM, making it an undesirable treatment option.

Corticosteroids often have been used to treat IGM, but their efficacy is variable, symptoms can recur upon drug removal, and remarkable AEs can result from long-term use.¹² Additionally, corticosteroid therapy often is used in combination with excision, making it difficult to determine the extent to which corticosteroids or excision are more beneficial. In a prospective observational study, corticosteroid therapy alone resolved 80% of IGM symptoms after 159 days on average. After complete symptom resolution, 23% of patients had disease recurrence.⁹ Observed AEs included gastritis, weight gain, osteoporosis, glucose intolerance, and Cushing syndrome.^12,15

Methotrexate for IGM has not been reviewed in a randomized controlled trial; case reports have shown 83% symptom resolution, with 17% recurrence and limited long-term AEs.¹² Because the active phase of IGM can persist for 2 years, immunosuppressive therapy with limited AEs is necessary. Many AEs can occur when high-dose methotrexate is given for cancer treatment. Low-dose methotrexate has been extensively studied in long-term treatment of rheumatoid arthritis. Adverse effects may include gastrointestinal tract upset and hepatic dysfunction, which are limited when given with folic acid.

Regardless of folic acid cotreatment, stomatitis may occur. Women should use an effective method of birth control because severe birth defects may occur on even low-dose methotrexate.¹⁶

Compared to corticosteroid or surgical treatment, we recommend low-dose methotrexate therapy based on its high efficacy with limited AEs. An occasional mild flare of IGM symptoms with methotrexate is not unusual. If it occurs, corticosteroids can be added and tapered for as long as 2 weeks to speed up resolution of flares while reducing long-term AEs of corticosteroids.

Surgical excision can be performed in cases refractory to all systemic therapies.

CONCLUSION

Idiopathic granulomatous mastitis is a rare granulomatous breast disorder that can have a prolonged time to diagnosis, delaying proper treatment. Many cases self-resolve, but more severe cases can persist for a long period before adequate symptomatic treatment is achieved by methotrexate, corticosteroids, or surgical excision. Before using these therapies, it is important to identify and remove contributing factors, such as long-term breastfeeding and drugs that induce hyperprolactinemia. Improving the rate of IGM diagnosis and treatment would greatly benefit these patients. We report 1 case in which removal of possible precipitating IGM factors led to symptom resolution and 2 cases in which methotrexate was an effective IGM treatment that limited the need for invasive procedures and corticosteroid AEs.

En coup de sabre (ECDS) is a rare subtype of linear scleroderma that is limited to the hemiface in a unilateral distribution. The lesional skin first exhibits contraction and stiffness that lead to characteristic fibrotic plaques with associated linear alopecia.¹ The pansclerotic plaques are ivory in color with hyperpigmented to violaceous borders extending as a paramedian band on the frontoparietal scalp.^2,3 The skin lesions bear resemblance to the stroke of the sabre sword, giving the condition its unique name. Many patients initially present with concerns of frontal scalp alopecia.³ Linear morphea, including the ECDS subtype, is predominantly seen in children and women, usually presenting within the first 2 decades of life.^1,4

The differential diagnoses of ECDS include focal dermal hypoplasia, steroid atrophy, localized morphea, and lupus profundus.⁵ En coup de sabre should be distinguished from progressive hemifacial atrophy (PHA)(also known as Parry-Romberg syndrome).⁶ Progressive hemifacial atrophy presents as unilateral atrophy of the face involving skin, subcutaneous tissue, muscle, and underlying bone in the distribution of the trigeminal nerve.¹ Both PHA and ECDS exist on a spectrum of linear scleroderma and may coexist in the same patient.⁶

There is a strong association with extracutaneous neurologic involvement, including seizures, ocular abnormalities, trigeminal neuralgia, and headache.^7-10 One study examining ECDS and PHA demonstrated that 44% (19/43) of patients who underwent central nervous system imaging had abnormal findings.¹¹ The majority of patients had magnetic resonance imaging with or without contrast, computed tomography, or both. The most common findings on T2-weighted images were white matter hyperintensities, mostly in subcortical and periventricular regions. The findings were bilateral in 61% (11/18) of patients and ipsilateral to the lesion in 33% (6/18) of patients.¹¹ We present a case of ECDS masquerading as alopecia in a 77-year-old woman.

Case Report

A 77-year-old white woman presented with a chief concern of hair loss on the scalp that had been present since 12 years of age. During her adult life, the scalp lesion remained unchanged with no associated symptoms. Her medical history was remarkable for hypertension and non–insulin-dependent diabetes mellitus. The patient denied any history of seizure disorders, facial paralysis, or neurologic deficits. Physical examination revealed a 13.6-cm linear, alopecic, hyperpigmented plaque extending from the left forehead and temporal scalp to the posterior occipital scalp with notable loss of underlying subcutaneous tissue (Figure). The left temporal scalp and forehead demonstrated pronounced atrophy with overlying telangiectases. Minimal depression was observed in the temporal scalp and forehead. The left cranial bone was easily palpable with no underlying subcutaneous tissue present. Computed tomography of the brain revealed no underlying skull or soft tissue abnormalities. No treatment was initiated, as the lesion was of minimal concern to the patient.

Comment

Etiology and Presentation                                                                                                                                                                                                                                      
En coup de sabre is a rare subtype of linear morphea that involves the frontoparietal scalp and forehead.^7,12,13 It manifests as a solitary, linear, fibrous plaque that involves the skin, underlying muscle, and bone.⁷ Although most cases present with a single lesion, multiple lesions can occur.⁸ The exact etiology of this disease remains to be determined but is characterized by thickening and hardening of the skin secondary to increased collagen production.⁷ The incidence of linear morphea ranges from 0.4 to 2.7 cases per 100,000 individuals and is more prevalent in white patients and women.¹⁴ Linear morphea is commonly found in children. Children are more likely to have linear morphea on the face, which can lead to lifelong disfigurement.² Although the disease peaks in the fourth decade of life for adults, most pediatric cases are diagnosed between 2 and 14 years of age.^14-16

Pathogenesis                                                                                                                                                                                                                                                       
Clinical and histopathological data suggest that a complex interaction among the vasculature, extracellular matrix, and immune system plays a role in the pathogenesis of the disease. Similar to scleroderma, the CD4 helper T cell may be involved in the fibrotic changes that occur within these lesions.¹⁷ Early in the disease process, T_H1 and T_H17 inflammatory pathways predominate. The late fibrotic changes seen in scleroderma are more associated with a shift to the T_H2 inflammatory pathway.¹⁷ Infection with Borrelia burgdorferi has been implicated abroad, but a large-scale study confirming Borrelia as a pathologic factor within morphea lesions has not been completed to date.^18-20 Some authors believe early lesions of ECDS mimic erythema chronica migrans, with the late lesions resembling acrodermatitis chronica atrophicans.²⁰

Histopathology                                                                                                                                                                                                                                     
Histopathologic findings of morphea tend to vary depending on the stage of the disease. The 2 stages of morphea can be differentiated by the degree of inflammation present histologically.^14,21 The early phase of morphea primarily affects the connective and subcutaneous tissue surrounding eccrine sweat glands.^14,21 A dense dermal and subcutaneous perivascular lymphocytic infiltrate with a mixture of lymphocytes, plasma cells, and histiocytes is commonly observed.⁵ Later stages of the disease demonstrate densely packed homogenous collagen with minimal inflammation and loss of eccrine glands and blood vessels.^14,21 The adipose tissue is generally replaced by sclerotic collagen, giving the biopsy a squared-off appearance.^5,14

Management                                                                                                                                                                                                                                                            
En coup de sabre presents a treatment challenge. In active lesions, topical or intralesional corticosteroids are considered treatment of choice.⁵ Methotrexate has proven useful in the treatment of acute and deep forms of linear morphea. A study examining methotrexate in juvenile localized scleroderma, with the majority of patients having the linear subtype, revealed that methotrexate is both efficacious and well tolerated.²² Other reports in the literature reveal efficacy with the use of intravenous corticosteroids and methotrexate combination therapy for treatment of morphea.^23,24 A longitudinal prospective study examining the use of high-dose methotrexate and oral corticosteroids for the treatment of localized scleroderma yielded positive results, with patients showing clinical improvement within 2 months of initiation of combination therapy.²⁵ Other treatments include excimer laser; calcipotriene and tacrolimus; and surgical approaches such as autologous fat grafting, grafting with muscle flaps, and tissue inserts.^21,26-31 In addition, patients can choose to forego therapy, as was the case with our patient.

Conclusion

En coup de sabre is a rare subtype of linear scleroderma that is limited to the ipsilateral scalp and face predominately in children and women. Neurologic involvement is common and should prompt a comprehensive neurologic workup in patients suspected to have ECDS or PHA. Current treatment recommendations include topical, intralesional, and oral corticosteroids; methotrexate; and surgical grafts. Although ECDS is a rare entity, more intensive research is needed on the exact pathophysiology and effective treatment options that focus on improving the cosmetic outcome in these patients. Cosmesis is the primary concern in patients with ECDS and should be managed early and appropriately to prevent long-term psychological sequelae.

En coup de sabre (ECDS) is a rare subtype of linear scleroderma that is limited to the hemiface in a unilateral distribution. The lesional skin first exhibits contraction and stiffness that lead to characteristic fibrotic plaques with associated linear alopecia.¹ The pansclerotic plaques are ivory in color with hyperpigmented to violaceous borders extending as a paramedian band on the frontoparietal scalp.^2,3 The skin lesions bear resemblance to the stroke of the sabre sword, giving the condition its unique name. Many patients initially present with concerns of frontal scalp alopecia.³ Linear morphea, including the ECDS subtype, is predominantly seen in children and women, usually presenting within the first 2 decades of life.^1,4

The differential diagnoses of ECDS include focal dermal hypoplasia, steroid atrophy, localized morphea, and lupus profundus.⁵ En coup de sabre should be distinguished from progressive hemifacial atrophy (PHA)(also known as Parry-Romberg syndrome).⁶ Progressive hemifacial atrophy presents as unilateral atrophy of the face involving skin, subcutaneous tissue, muscle, and underlying bone in the distribution of the trigeminal nerve.¹ Both PHA and ECDS exist on a spectrum of linear scleroderma and may coexist in the same patient.⁶

There is a strong association with extracutaneous neurologic involvement, including seizures, ocular abnormalities, trigeminal neuralgia, and headache.^7-10 One study examining ECDS and PHA demonstrated that 44% (19/43) of patients who underwent central nervous system imaging had abnormal findings.¹¹ The majority of patients had magnetic resonance imaging with or without contrast, computed tomography, or both. The most common findings on T2-weighted images were white matter hyperintensities, mostly in subcortical and periventricular regions. The findings were bilateral in 61% (11/18) of patients and ipsilateral to the lesion in 33% (6/18) of patients.¹¹ We present a case of ECDS masquerading as alopecia in a 77-year-old woman.

Case Report

A 77-year-old white woman presented with a chief concern of hair loss on the scalp that had been present since 12 years of age. During her adult life, the scalp lesion remained unchanged with no associated symptoms. Her medical history was remarkable for hypertension and non–insulin-dependent diabetes mellitus. The patient denied any history of seizure disorders, facial paralysis, or neurologic deficits. Physical examination revealed a 13.6-cm linear, alopecic, hyperpigmented plaque extending from the left forehead and temporal scalp to the posterior occipital scalp with notable loss of underlying subcutaneous tissue (Figure). The left temporal scalp and forehead demonstrated pronounced atrophy with overlying telangiectases. Minimal depression was observed in the temporal scalp and forehead. The left cranial bone was easily palpable with no underlying subcutaneous tissue present. Computed tomography of the brain revealed no underlying skull or soft tissue abnormalities. No treatment was initiated, as the lesion was of minimal concern to the patient.

Comment

Etiology and Presentation                                                                                                                                                                                                                                      
En coup de sabre is a rare subtype of linear morphea that involves the frontoparietal scalp and forehead.^7,12,13 It manifests as a solitary, linear, fibrous plaque that involves the skin, underlying muscle, and bone.⁷ Although most cases present with a single lesion, multiple lesions can occur.⁸ The exact etiology of this disease remains to be determined but is characterized by thickening and hardening of the skin secondary to increased collagen production.⁷ The incidence of linear morphea ranges from 0.4 to 2.7 cases per 100,000 individuals and is more prevalent in white patients and women.¹⁴ Linear morphea is commonly found in children. Children are more likely to have linear morphea on the face, which can lead to lifelong disfigurement.² Although the disease peaks in the fourth decade of life for adults, most pediatric cases are diagnosed between 2 and 14 years of age.^14-16

Pathogenesis                                                                                                                                                                                                                                                       
Clinical and histopathological data suggest that a complex interaction among the vasculature, extracellular matrix, and immune system plays a role in the pathogenesis of the disease. Similar to scleroderma, the CD4 helper T cell may be involved in the fibrotic changes that occur within these lesions.¹⁷ Early in the disease process, T_H1 and T_H17 inflammatory pathways predominate. The late fibrotic changes seen in scleroderma are more associated with a shift to the T_H2 inflammatory pathway.¹⁷ Infection with Borrelia burgdorferi has been implicated abroad, but a large-scale study confirming Borrelia as a pathologic factor within morphea lesions has not been completed to date.^18-20 Some authors believe early lesions of ECDS mimic erythema chronica migrans, with the late lesions resembling acrodermatitis chronica atrophicans.²⁰

Histopathology                                                                                                                                                                                                                                     
Histopathologic findings of morphea tend to vary depending on the stage of the disease. The 2 stages of morphea can be differentiated by the degree of inflammation present histologically.^14,21 The early phase of morphea primarily affects the connective and subcutaneous tissue surrounding eccrine sweat glands.^14,21 A dense dermal and subcutaneous perivascular lymphocytic infiltrate with a mixture of lymphocytes, plasma cells, and histiocytes is commonly observed.⁵ Later stages of the disease demonstrate densely packed homogenous collagen with minimal inflammation and loss of eccrine glands and blood vessels.^14,21 The adipose tissue is generally replaced by sclerotic collagen, giving the biopsy a squared-off appearance.^5,14

Management                                                                                                                                                                                                                                                            
En coup de sabre presents a treatment challenge. In active lesions, topical or intralesional corticosteroids are considered treatment of choice.⁵ Methotrexate has proven useful in the treatment of acute and deep forms of linear morphea. A study examining methotrexate in juvenile localized scleroderma, with the majority of patients having the linear subtype, revealed that methotrexate is both efficacious and well tolerated.²² Other reports in the literature reveal efficacy with the use of intravenous corticosteroids and methotrexate combination therapy for treatment of morphea.^23,24 A longitudinal prospective study examining the use of high-dose methotrexate and oral corticosteroids for the treatment of localized scleroderma yielded positive results, with patients showing clinical improvement within 2 months of initiation of combination therapy.²⁵ Other treatments include excimer laser; calcipotriene and tacrolimus; and surgical approaches such as autologous fat grafting, grafting with muscle flaps, and tissue inserts.^21,26-31 In addition, patients can choose to forego therapy, as was the case with our patient.

Conclusion

En coup de sabre is a rare subtype of linear scleroderma that is limited to the ipsilateral scalp and face predominately in children and women. Neurologic involvement is common and should prompt a comprehensive neurologic workup in patients suspected to have ECDS or PHA. Current treatment recommendations include topical, intralesional, and oral corticosteroids; methotrexate; and surgical grafts. Although ECDS is a rare entity, more intensive research is needed on the exact pathophysiology and effective treatment options that focus on improving the cosmetic outcome in these patients. Cosmesis is the primary concern in patients with ECDS and should be managed early and appropriately to prevent long-term psychological sequelae.

En coup de sabre (ECDS) is a rare subtype of linear scleroderma that is limited to the hemiface in a unilateral distribution. The lesional skin first exhibits contraction and stiffness that lead to characteristic fibrotic plaques with associated linear alopecia.¹ The pansclerotic plaques are ivory in color with hyperpigmented to violaceous borders extending as a paramedian band on the frontoparietal scalp.^2,3 The skin lesions bear resemblance to the stroke of the sabre sword, giving the condition its unique name. Many patients initially present with concerns of frontal scalp alopecia.³ Linear morphea, including the ECDS subtype, is predominantly seen in children and women, usually presenting within the first 2 decades of life.^1,4

The differential diagnoses of ECDS include focal dermal hypoplasia, steroid atrophy, localized morphea, and lupus profundus.⁵ En coup de sabre should be distinguished from progressive hemifacial atrophy (PHA)(also known as Parry-Romberg syndrome).⁶ Progressive hemifacial atrophy presents as unilateral atrophy of the face involving skin, subcutaneous tissue, muscle, and underlying bone in the distribution of the trigeminal nerve.¹ Both PHA and ECDS exist on a spectrum of linear scleroderma and may coexist in the same patient.⁶

There is a strong association with extracutaneous neurologic involvement, including seizures, ocular abnormalities, trigeminal neuralgia, and headache.^7-10 One study examining ECDS and PHA demonstrated that 44% (19/43) of patients who underwent central nervous system imaging had abnormal findings.¹¹ The majority of patients had magnetic resonance imaging with or without contrast, computed tomography, or both. The most common findings on T2-weighted images were white matter hyperintensities, mostly in subcortical and periventricular regions. The findings were bilateral in 61% (11/18) of patients and ipsilateral to the lesion in 33% (6/18) of patients.¹¹ We present a case of ECDS masquerading as alopecia in a 77-year-old woman.

Case Report

A 77-year-old white woman presented with a chief concern of hair loss on the scalp that had been present since 12 years of age. During her adult life, the scalp lesion remained unchanged with no associated symptoms. Her medical history was remarkable for hypertension and non–insulin-dependent diabetes mellitus. The patient denied any history of seizure disorders, facial paralysis, or neurologic deficits. Physical examination revealed a 13.6-cm linear, alopecic, hyperpigmented plaque extending from the left forehead and temporal scalp to the posterior occipital scalp with notable loss of underlying subcutaneous tissue (Figure). The left temporal scalp and forehead demonstrated pronounced atrophy with overlying telangiectases. Minimal depression was observed in the temporal scalp and forehead. The left cranial bone was easily palpable with no underlying subcutaneous tissue present. Computed tomography of the brain revealed no underlying skull or soft tissue abnormalities. No treatment was initiated, as the lesion was of minimal concern to the patient.

Comment

Etiology and Presentation                                                                                                                                                                                                                                      
En coup de sabre is a rare subtype of linear morphea that involves the frontoparietal scalp and forehead.^7,12,13 It manifests as a solitary, linear, fibrous plaque that involves the skin, underlying muscle, and bone.⁷ Although most cases present with a single lesion, multiple lesions can occur.⁸ The exact etiology of this disease remains to be determined but is characterized by thickening and hardening of the skin secondary to increased collagen production.⁷ The incidence of linear morphea ranges from 0.4 to 2.7 cases per 100,000 individuals and is more prevalent in white patients and women.¹⁴ Linear morphea is commonly found in children. Children are more likely to have linear morphea on the face, which can lead to lifelong disfigurement.² Although the disease peaks in the fourth decade of life for adults, most pediatric cases are diagnosed between 2 and 14 years of age.^14-16

Pathogenesis                                                                                                                                                                                                                                                       
Clinical and histopathological data suggest that a complex interaction among the vasculature, extracellular matrix, and immune system plays a role in the pathogenesis of the disease. Similar to scleroderma, the CD4 helper T cell may be involved in the fibrotic changes that occur within these lesions.¹⁷ Early in the disease process, T_H1 and T_H17 inflammatory pathways predominate. The late fibrotic changes seen in scleroderma are more associated with a shift to the T_H2 inflammatory pathway.¹⁷ Infection with Borrelia burgdorferi has been implicated abroad, but a large-scale study confirming Borrelia as a pathologic factor within morphea lesions has not been completed to date.^18-20 Some authors believe early lesions of ECDS mimic erythema chronica migrans, with the late lesions resembling acrodermatitis chronica atrophicans.²⁰

Histopathology                                                                                                                                                                                                                                     
Histopathologic findings of morphea tend to vary depending on the stage of the disease. The 2 stages of morphea can be differentiated by the degree of inflammation present histologically.^14,21 The early phase of morphea primarily affects the connective and subcutaneous tissue surrounding eccrine sweat glands.^14,21 A dense dermal and subcutaneous perivascular lymphocytic infiltrate with a mixture of lymphocytes, plasma cells, and histiocytes is commonly observed.⁵ Later stages of the disease demonstrate densely packed homogenous collagen with minimal inflammation and loss of eccrine glands and blood vessels.^14,21 The adipose tissue is generally replaced by sclerotic collagen, giving the biopsy a squared-off appearance.^5,14

Management                                                                                                                                                                                                                                                            
En coup de sabre presents a treatment challenge. In active lesions, topical or intralesional corticosteroids are considered treatment of choice.⁵ Methotrexate has proven useful in the treatment of acute and deep forms of linear morphea. A study examining methotrexate in juvenile localized scleroderma, with the majority of patients having the linear subtype, revealed that methotrexate is both efficacious and well tolerated.²² Other reports in the literature reveal efficacy with the use of intravenous corticosteroids and methotrexate combination therapy for treatment of morphea.^23,24 A longitudinal prospective study examining the use of high-dose methotrexate and oral corticosteroids for the treatment of localized scleroderma yielded positive results, with patients showing clinical improvement within 2 months of initiation of combination therapy.²⁵ Other treatments include excimer laser; calcipotriene and tacrolimus; and surgical approaches such as autologous fat grafting, grafting with muscle flaps, and tissue inserts.^21,26-31 In addition, patients can choose to forego therapy, as was the case with our patient.

Conclusion

En coup de sabre is a rare subtype of linear scleroderma that is limited to the ipsilateral scalp and face predominately in children and women. Neurologic involvement is common and should prompt a comprehensive neurologic workup in patients suspected to have ECDS or PHA. Current treatment recommendations include topical, intralesional, and oral corticosteroids; methotrexate; and surgical grafts. Although ECDS is a rare entity, more intensive research is needed on the exact pathophysiology and effective treatment options that focus on improving the cosmetic outcome in these patients. Cosmesis is the primary concern in patients with ECDS and should be managed early and appropriately to prevent long-term psychological sequelae.

Pityriasis amiantacea (PA) is characterized by adherence of hair shafts proximally.¹ It has been associated with dermatologic conditions and rarely with medications. We describe a woman who developed PA following a bone marrow transplant with melphalan conditioning. We also review drug-induced PA and disorders that have been linked to this condition.

Case Report

A 67-year-old woman with a history of multiple myeloma was treated with 7 courses of chemotherapy (cyclophosphamide, bortezomib, prednisone). One month later, the patient underwent a bone marrow transplant with melphalan conditioning due to residual plasma cell myeloma. Following the transplant, she developed complete scalp alopecia. Prior to and following transplant, the patient’s hair care regimen included washing her hair and scalp every other day with over-the-counter “natural” shampoos. During drug-induced alopecia, the hair washing became less frequent.

The patient left the hospital 4 weeks posttransplant; her hair had started to regrow, but its appearance was altered. Posttransplant, the patient was maintained on bortezomib every other week and zoledronate once per month. She continued to develop multiple lesions in the scalp hairs during the following 4 months.

Eight months posttransplant she presented for evaluation of the scalp hair. Clinical examination showed hairs that were entwined together proximally, resulting in matting of the hair (Figure 1). A diagnosis of PA was established based on the clinical examination.

Treatment included mineral oil application to the scalp under occlusion each evening, followed by morning washing with coal tar 0.5%, salicylic acid 6%, or ketoconazole 2% shampoo in a repeating sequential manner. Within 1 month there was complete resolution of the scalp condition (Figure 2).

Comment

Clinical Presentation                                                                                                                                                                                                                                                                                                                                                             
Pityriasis amiantacea is characterized by thick excessive scale of the scalp¹; it was initially described by Alibert² in 1832. He described the gross appearance of the scales as resembling the feathers of young birds, which naturalists dub “amiante” or asbestoslike.^1,2 In 1917, Gougerot³ explored infectious etiologies of this condition by describing cases of impetigo that transitioned into PA.¹ Later, in 1929, Photinos⁴ described fungal origins of PA, giving credence to “tinea amiantacea.”¹ However, more recent analyses failed to isolate fungus.^5-7 As such, pityriasis (scaling) amiantacea is the more appropriate term, as emphasized by Brown⁸ in 1948. The cause of PA remains unclear; it is hypothesized that the condition is a reaction to underlying inflammatory dermatoses, though concurrent bacterial or fungal infection may be present.^5,9

Prevalence                                                                                                                                                                                                                                                                                                                                                                             
Pityriasis amiantacea is considered to be most prevalent in pediatric patients and young adults; it is more common in females.^1,9,10 In a review of 85 PA patients, more than 80% were women (n=69), and the mean age at presentation was 23.8 years. Approximately half of these patients had widespread scalp lesions (n=42); however, focal localized lesions were common.⁹ No hereditary patterns have been described, though 3 pairs of the 10 patients with PA in Ring and Kaplan’s⁷ review were siblings.

Histopathology                                                                                                                                                                                                                                                                                                                                                                 
Submission of hair specimens to histopathology usually is not performed since the diagnosis often is established based on the clinical presentation.⁵ However, submitted specimens have demonstrated spongiosis and parakeratosis along with reduction in the size of the sebaceous glands.^1,9 Additionally, follicular keratosis that surrounds the hair shafts with a sheath of horn is present.⁹ Acanthosis and migration of lymphocytes into the epidermis also have been found.¹ Often, Staphylococcus aureus isolates are detected.^9,13
 

Differential Diagnosis                                                                                                                                                                                                                                                                                                                                                                   
The clinical differential diagnosis of PA includes hair casts,¹¹ pediculosis,¹⁴ and tinea capitis.¹² In PA, thick scales surround hair shafts and thus bind down tufts of hair.⁹ In patients with pediculosis, nits are attached to the hair shaft at an angle and do not entirely envelop the hair shaft.¹⁴ In addition, PA may be complicated by impetiginization; bacteria often are found in the keratin surrounding the hair shaft and represent either normal flora or secondary infection.^1,15 It has been speculated that microbial biofilms from S aureus and Staphylococcus epidermidis promote agglomeration of hair shafts and adherent scale.¹⁶ Bona fide dermatophyte infection of the scalp also may be concurrently present.¹²

Treatment                                                                                                                                                                                                                                                                                                                                                                                     
Our treatment included occlusion with mineral oil to loosen the scales from the scalp in tandem with shampoos traditionally used in patients with seborrheic dermatitis or psoriasis. Timely treatment is important to prevent scarring alopecia.^13,17 Pityriasis amiantacea may be treatment resistant, and there are no specific therapeutic guidelines; rather, therapy should be targeted at the suspected underlying condition.¹⁷ Treatment generally includes keratolytic agents, such as salicylic acid.¹⁸ These agents allow enhanced penetration of other topical agents.¹⁹ Topical antifungal shampoos such as ketoconazole and ciclopirox are recommended,¹⁸ though other topical agents, such as coal tar and zinc pyrithione, also may benefit patients.¹³ Topical corticosteroids may be used if the condition is linked with psoriasis.¹³ Systemic antibiotics are added if S aureus superinfection is suspected.⁹

A single report described successful management of a patient with severe refractory PA who was treated with the tumor necrosis factor (TNF) α inhibitor infliximab.¹³ A 47-year-old woman presented with thick adherent scale on the scalp. She was treated with coal tar for 18 months but showed no improvement; the patient was subsequently prescribed salicylic acid 10%, clobetasol solution, and coal tar shampoo. After 3 months, when no improvement was observed, the patient was offered infliximab but declined. For 6 years the patient was treated with salicylic acid 20%, clobetasol (foam, lotion, shampoo, and solution), and coal tar shampoo without improvement. She then consented to infliximab therapy; after 3 infusions at weeks 0, 2, and 6, she demonstrated notable improvement. The patient was maintained on infliximab every 8 weeks.¹³

Pathogenesis                                                                                                                                                                                                                                                                                                                                                                                 
The pathogenesis of PA has yet to be definitively established, and the condition is usually idiopathic. In addition to bacterial or fungal etiologies,^3,4 PA has been linked to medications (Table 1)^16,20,21 and systemic conditions (Table 2).^{1,3,5,7-10,12,22-25}

A PubMed search of articles indexed for MEDLINE using the search terms amiantacea, bone, drug, hair marrow, malignancy, melphalan, pityriasis, tinea, and transplant yielded 4 patients—2 men and 2 women (including our patient)—with possible drug-induced PA (Table 1)^16,20,21; however, the onset after 2 years of medication (TNF-α inhibitors) or resolution while still receiving the agent (vemurafenib) makes the drug-induced linkage weak. The patients ranged in age from 21 to 67 years, with the median age being 37.5 years. Medications included melphalan, TNF-α inhibitors (adalimumab, infliximab),^16,21 and vemurafenib²⁰; it is interesting that infliximab was the medication associated with eliciting PA in 1 patient yet was an effective therapy in another patient with treatment-resistant PA. The onset of PA occurred between 1 month (melphalan) and 24 months (TNF-α inhibitors) after drug initiation. The patients’ associated diseases included Crohn disease,^16,21 metastatic melanoma,²⁰ and multiple myeloma.

Other conditions have been described in patients with PA (Table 2). Indeed, PA may be a manifestation of an underlying inflammatory skin disease.⁹ In addition to dermatologic conditions, procedures or malignancy may be associated with the disease, as demonstrated in our patient. Most commonly, PA is seen in association with psoriasis and seborrheic dermatitis; atopic dermatitis, bacterial infection, fungal infection, lichen planus, and neurodermatitis also have been associated with PA.^{1,3,5,7-10,12,18,22-25}

Conclusion

Pityriasis amiantacea is a benign condition affecting the scalp hair. Albeit uncommon, it may appear in patients treated with medications such as melphalan, TNF-α inhibitors, and vemurafenib. In addition, it has been described in individuals with dermatologic conditions, systemic procedures, or underlying malignancy. Our patient developed PA following a bone marrow transplant after receiving conditioning with melphalan.

Pityriasis amiantacea (PA) is characterized by adherence of hair shafts proximally.¹ It has been associated with dermatologic conditions and rarely with medications. We describe a woman who developed PA following a bone marrow transplant with melphalan conditioning. We also review drug-induced PA and disorders that have been linked to this condition.

Case Report

A 67-year-old woman with a history of multiple myeloma was treated with 7 courses of chemotherapy (cyclophosphamide, bortezomib, prednisone). One month later, the patient underwent a bone marrow transplant with melphalan conditioning due to residual plasma cell myeloma. Following the transplant, she developed complete scalp alopecia. Prior to and following transplant, the patient’s hair care regimen included washing her hair and scalp every other day with over-the-counter “natural” shampoos. During drug-induced alopecia, the hair washing became less frequent.

The patient left the hospital 4 weeks posttransplant; her hair had started to regrow, but its appearance was altered. Posttransplant, the patient was maintained on bortezomib every other week and zoledronate once per month. She continued to develop multiple lesions in the scalp hairs during the following 4 months.

Eight months posttransplant she presented for evaluation of the scalp hair. Clinical examination showed hairs that were entwined together proximally, resulting in matting of the hair (Figure 1). A diagnosis of PA was established based on the clinical examination.

Treatment included mineral oil application to the scalp under occlusion each evening, followed by morning washing with coal tar 0.5%, salicylic acid 6%, or ketoconazole 2% shampoo in a repeating sequential manner. Within 1 month there was complete resolution of the scalp condition (Figure 2).

Comment

Clinical Presentation                                                                                                                                                                                                                                                                                                                                                             
Pityriasis amiantacea is characterized by thick excessive scale of the scalp¹; it was initially described by Alibert² in 1832. He described the gross appearance of the scales as resembling the feathers of young birds, which naturalists dub “amiante” or asbestoslike.^1,2 In 1917, Gougerot³ explored infectious etiologies of this condition by describing cases of impetigo that transitioned into PA.¹ Later, in 1929, Photinos⁴ described fungal origins of PA, giving credence to “tinea amiantacea.”¹ However, more recent analyses failed to isolate fungus.^5-7 As such, pityriasis (scaling) amiantacea is the more appropriate term, as emphasized by Brown⁸ in 1948. The cause of PA remains unclear; it is hypothesized that the condition is a reaction to underlying inflammatory dermatoses, though concurrent bacterial or fungal infection may be present.^5,9

Prevalence                                                                                                                                                                                                                                                                                                                                                                             
Pityriasis amiantacea is considered to be most prevalent in pediatric patients and young adults; it is more common in females.^1,9,10 In a review of 85 PA patients, more than 80% were women (n=69), and the mean age at presentation was 23.8 years. Approximately half of these patients had widespread scalp lesions (n=42); however, focal localized lesions were common.⁹ No hereditary patterns have been described, though 3 pairs of the 10 patients with PA in Ring and Kaplan’s⁷ review were siblings.

Histopathology                                                                                                                                                                                                                                                                                                                                                                 
Submission of hair specimens to histopathology usually is not performed since the diagnosis often is established based on the clinical presentation.⁵ However, submitted specimens have demonstrated spongiosis and parakeratosis along with reduction in the size of the sebaceous glands.^1,9 Additionally, follicular keratosis that surrounds the hair shafts with a sheath of horn is present.⁹ Acanthosis and migration of lymphocytes into the epidermis also have been found.¹ Often, Staphylococcus aureus isolates are detected.^9,13
 

Differential Diagnosis                                                                                                                                                                                                                                                                                                                                                                   
The clinical differential diagnosis of PA includes hair casts,¹¹ pediculosis,¹⁴ and tinea capitis.¹² In PA, thick scales surround hair shafts and thus bind down tufts of hair.⁹ In patients with pediculosis, nits are attached to the hair shaft at an angle and do not entirely envelop the hair shaft.¹⁴ In addition, PA may be complicated by impetiginization; bacteria often are found in the keratin surrounding the hair shaft and represent either normal flora or secondary infection.^1,15 It has been speculated that microbial biofilms from S aureus and Staphylococcus epidermidis promote agglomeration of hair shafts and adherent scale.¹⁶ Bona fide dermatophyte infection of the scalp also may be concurrently present.¹²

Treatment                                                                                                                                                                                                                                                                                                                                                                                     
Our treatment included occlusion with mineral oil to loosen the scales from the scalp in tandem with shampoos traditionally used in patients with seborrheic dermatitis or psoriasis. Timely treatment is important to prevent scarring alopecia.^13,17 Pityriasis amiantacea may be treatment resistant, and there are no specific therapeutic guidelines; rather, therapy should be targeted at the suspected underlying condition.¹⁷ Treatment generally includes keratolytic agents, such as salicylic acid.¹⁸ These agents allow enhanced penetration of other topical agents.¹⁹ Topical antifungal shampoos such as ketoconazole and ciclopirox are recommended,¹⁸ though other topical agents, such as coal tar and zinc pyrithione, also may benefit patients.¹³ Topical corticosteroids may be used if the condition is linked with psoriasis.¹³ Systemic antibiotics are added if S aureus superinfection is suspected.⁹

A single report described successful management of a patient with severe refractory PA who was treated with the tumor necrosis factor (TNF) α inhibitor infliximab.¹³ A 47-year-old woman presented with thick adherent scale on the scalp. She was treated with coal tar for 18 months but showed no improvement; the patient was subsequently prescribed salicylic acid 10%, clobetasol solution, and coal tar shampoo. After 3 months, when no improvement was observed, the patient was offered infliximab but declined. For 6 years the patient was treated with salicylic acid 20%, clobetasol (foam, lotion, shampoo, and solution), and coal tar shampoo without improvement. She then consented to infliximab therapy; after 3 infusions at weeks 0, 2, and 6, she demonstrated notable improvement. The patient was maintained on infliximab every 8 weeks.¹³

Pathogenesis                                                                                                                                                                                                                                                                                                                                                                                 
The pathogenesis of PA has yet to be definitively established, and the condition is usually idiopathic. In addition to bacterial or fungal etiologies,^3,4 PA has been linked to medications (Table 1)^16,20,21 and systemic conditions (Table 2).^{1,3,5,7-10,12,22-25}

A PubMed search of articles indexed for MEDLINE using the search terms amiantacea, bone, drug, hair marrow, malignancy, melphalan, pityriasis, tinea, and transplant yielded 4 patients—2 men and 2 women (including our patient)—with possible drug-induced PA (Table 1)^16,20,21; however, the onset after 2 years of medication (TNF-α inhibitors) or resolution while still receiving the agent (vemurafenib) makes the drug-induced linkage weak. The patients ranged in age from 21 to 67 years, with the median age being 37.5 years. Medications included melphalan, TNF-α inhibitors (adalimumab, infliximab),^16,21 and vemurafenib²⁰; it is interesting that infliximab was the medication associated with eliciting PA in 1 patient yet was an effective therapy in another patient with treatment-resistant PA. The onset of PA occurred between 1 month (melphalan) and 24 months (TNF-α inhibitors) after drug initiation. The patients’ associated diseases included Crohn disease,^16,21 metastatic melanoma,²⁰ and multiple myeloma.

Other conditions have been described in patients with PA (Table 2). Indeed, PA may be a manifestation of an underlying inflammatory skin disease.⁹ In addition to dermatologic conditions, procedures or malignancy may be associated with the disease, as demonstrated in our patient. Most commonly, PA is seen in association with psoriasis and seborrheic dermatitis; atopic dermatitis, bacterial infection, fungal infection, lichen planus, and neurodermatitis also have been associated with PA.^{1,3,5,7-10,12,18,22-25}

Conclusion

Pityriasis amiantacea is a benign condition affecting the scalp hair. Albeit uncommon, it may appear in patients treated with medications such as melphalan, TNF-α inhibitors, and vemurafenib. In addition, it has been described in individuals with dermatologic conditions, systemic procedures, or underlying malignancy. Our patient developed PA following a bone marrow transplant after receiving conditioning with melphalan.

Pityriasis amiantacea (PA) is characterized by adherence of hair shafts proximally.¹ It has been associated with dermatologic conditions and rarely with medications. We describe a woman who developed PA following a bone marrow transplant with melphalan conditioning. We also review drug-induced PA and disorders that have been linked to this condition.

Case Report

A 67-year-old woman with a history of multiple myeloma was treated with 7 courses of chemotherapy (cyclophosphamide, bortezomib, prednisone). One month later, the patient underwent a bone marrow transplant with melphalan conditioning due to residual plasma cell myeloma. Following the transplant, she developed complete scalp alopecia. Prior to and following transplant, the patient’s hair care regimen included washing her hair and scalp every other day with over-the-counter “natural” shampoos. During drug-induced alopecia, the hair washing became less frequent.

The patient left the hospital 4 weeks posttransplant; her hair had started to regrow, but its appearance was altered. Posttransplant, the patient was maintained on bortezomib every other week and zoledronate once per month. She continued to develop multiple lesions in the scalp hairs during the following 4 months.

Eight months posttransplant she presented for evaluation of the scalp hair. Clinical examination showed hairs that were entwined together proximally, resulting in matting of the hair (Figure 1). A diagnosis of PA was established based on the clinical examination.

Treatment included mineral oil application to the scalp under occlusion each evening, followed by morning washing with coal tar 0.5%, salicylic acid 6%, or ketoconazole 2% shampoo in a repeating sequential manner. Within 1 month there was complete resolution of the scalp condition (Figure 2).

Comment

Clinical Presentation                                                                                                                                                                                                                                                                                                                                                             
Pityriasis amiantacea is characterized by thick excessive scale of the scalp¹; it was initially described by Alibert² in 1832. He described the gross appearance of the scales as resembling the feathers of young birds, which naturalists dub “amiante” or asbestoslike.^1,2 In 1917, Gougerot³ explored infectious etiologies of this condition by describing cases of impetigo that transitioned into PA.¹ Later, in 1929, Photinos⁴ described fungal origins of PA, giving credence to “tinea amiantacea.”¹ However, more recent analyses failed to isolate fungus.^5-7 As such, pityriasis (scaling) amiantacea is the more appropriate term, as emphasized by Brown⁸ in 1948. The cause of PA remains unclear; it is hypothesized that the condition is a reaction to underlying inflammatory dermatoses, though concurrent bacterial or fungal infection may be present.^5,9

Prevalence                                                                                                                                                                                                                                                                                                                                                                             
Pityriasis amiantacea is considered to be most prevalent in pediatric patients and young adults; it is more common in females.^1,9,10 In a review of 85 PA patients, more than 80% were women (n=69), and the mean age at presentation was 23.8 years. Approximately half of these patients had widespread scalp lesions (n=42); however, focal localized lesions were common.⁹ No hereditary patterns have been described, though 3 pairs of the 10 patients with PA in Ring and Kaplan’s⁷ review were siblings.

Histopathology                                                                                                                                                                                                                                                                                                                                                                 
Submission of hair specimens to histopathology usually is not performed since the diagnosis often is established based on the clinical presentation.⁵ However, submitted specimens have demonstrated spongiosis and parakeratosis along with reduction in the size of the sebaceous glands.^1,9 Additionally, follicular keratosis that surrounds the hair shafts with a sheath of horn is present.⁹ Acanthosis and migration of lymphocytes into the epidermis also have been found.¹ Often, Staphylococcus aureus isolates are detected.^9,13
 

Differential Diagnosis                                                                                                                                                                                                                                                                                                                                                                   
The clinical differential diagnosis of PA includes hair casts,¹¹ pediculosis,¹⁴ and tinea capitis.¹² In PA, thick scales surround hair shafts and thus bind down tufts of hair.⁹ In patients with pediculosis, nits are attached to the hair shaft at an angle and do not entirely envelop the hair shaft.¹⁴ In addition, PA may be complicated by impetiginization; bacteria often are found in the keratin surrounding the hair shaft and represent either normal flora or secondary infection.^1,15 It has been speculated that microbial biofilms from S aureus and Staphylococcus epidermidis promote agglomeration of hair shafts and adherent scale.¹⁶ Bona fide dermatophyte infection of the scalp also may be concurrently present.¹²

Treatment                                                                                                                                                                                                                                                                                                                                                                                     
Our treatment included occlusion with mineral oil to loosen the scales from the scalp in tandem with shampoos traditionally used in patients with seborrheic dermatitis or psoriasis. Timely treatment is important to prevent scarring alopecia.^13,17 Pityriasis amiantacea may be treatment resistant, and there are no specific therapeutic guidelines; rather, therapy should be targeted at the suspected underlying condition.¹⁷ Treatment generally includes keratolytic agents, such as salicylic acid.¹⁸ These agents allow enhanced penetration of other topical agents.¹⁹ Topical antifungal shampoos such as ketoconazole and ciclopirox are recommended,¹⁸ though other topical agents, such as coal tar and zinc pyrithione, also may benefit patients.¹³ Topical corticosteroids may be used if the condition is linked with psoriasis.¹³ Systemic antibiotics are added if S aureus superinfection is suspected.⁹

A single report described successful management of a patient with severe refractory PA who was treated with the tumor necrosis factor (TNF) α inhibitor infliximab.¹³ A 47-year-old woman presented with thick adherent scale on the scalp. She was treated with coal tar for 18 months but showed no improvement; the patient was subsequently prescribed salicylic acid 10%, clobetasol solution, and coal tar shampoo. After 3 months, when no improvement was observed, the patient was offered infliximab but declined. For 6 years the patient was treated with salicylic acid 20%, clobetasol (foam, lotion, shampoo, and solution), and coal tar shampoo without improvement. She then consented to infliximab therapy; after 3 infusions at weeks 0, 2, and 6, she demonstrated notable improvement. The patient was maintained on infliximab every 8 weeks.¹³

Pathogenesis                                                                                                                                                                                                                                                                                                                                                                                 
The pathogenesis of PA has yet to be definitively established, and the condition is usually idiopathic. In addition to bacterial or fungal etiologies,^3,4 PA has been linked to medications (Table 1)^16,20,21 and systemic conditions (Table 2).^{1,3,5,7-10,12,22-25}

A PubMed search of articles indexed for MEDLINE using the search terms amiantacea, bone, drug, hair marrow, malignancy, melphalan, pityriasis, tinea, and transplant yielded 4 patients—2 men and 2 women (including our patient)—with possible drug-induced PA (Table 1)^16,20,21; however, the onset after 2 years of medication (TNF-α inhibitors) or resolution while still receiving the agent (vemurafenib) makes the drug-induced linkage weak. The patients ranged in age from 21 to 67 years, with the median age being 37.5 years. Medications included melphalan, TNF-α inhibitors (adalimumab, infliximab),^16,21 and vemurafenib²⁰; it is interesting that infliximab was the medication associated with eliciting PA in 1 patient yet was an effective therapy in another patient with treatment-resistant PA. The onset of PA occurred between 1 month (melphalan) and 24 months (TNF-α inhibitors) after drug initiation. The patients’ associated diseases included Crohn disease,^16,21 metastatic melanoma,²⁰ and multiple myeloma.

Other conditions have been described in patients with PA (Table 2). Indeed, PA may be a manifestation of an underlying inflammatory skin disease.⁹ In addition to dermatologic conditions, procedures or malignancy may be associated with the disease, as demonstrated in our patient. Most commonly, PA is seen in association with psoriasis and seborrheic dermatitis; atopic dermatitis, bacterial infection, fungal infection, lichen planus, and neurodermatitis also have been associated with PA.^{1,3,5,7-10,12,18,22-25}

Conclusion

Pityriasis amiantacea is a benign condition affecting the scalp hair. Albeit uncommon, it may appear in patients treated with medications such as melphalan, TNF-α inhibitors, and vemurafenib. In addition, it has been described in individuals with dermatologic conditions, systemic procedures, or underlying malignancy. Our patient developed PA following a bone marrow transplant after receiving conditioning with melphalan.

Abstract

Primary heart sarcomas are rare and represent 20% of all primary cardiac tumors. Symptoms depend on which chambers and cardiac structures are involved. Angiosarcoma is one of the most common and the most aggressive types of primary heart sarcomas. Typically, these tumors are found in the right atrium, however, cardiac angiosarcomas may involve any part of the heart. Most of these tumors are diagnosed in advanced stages and the patient prognosis is poor. Most tumors are diagnosed using echocardiography. Computed tomography (CT) and magnetic resonance imaging (MRI) provide useful information on tumor size and location for planning surgery, which is the only treatment shown to increase survival.  We present the case of a 69-year-old woman who presented to the emergency department with hypotension, dyspnea and progressive shortness of breath. After adequate resuscitation, a cardiac mass was identified and surgery was successfully performed. Pathology confirmed a grade 2 primary heart angiosarcoma. Following surgery, the patient was admitted to the intensive care unit and later died secondary to multi-organ system failure.

Introduction

Primary heart angiosarcoma is an aggressive and usually fatal cardiac neoplasm (1). Angiosarcomas can originate at any location in the heart (2, 3), but these tumors typically reside in the right atrium and frequently cause nonspecific symptoms such as dyspnea, cough, heart failure, and arrhythmias. (2) Surgery followed by chemotherapy is the typical approach to these tumors. (4)

We present the case of a 69-year-old woman who presented to the emergency department with hypotension and severe dyspnea.

Case Report

The patient was a 69-year-old woman with a medical history of diabetes. A week before seeking care in the emergency department, she experienced a general feeling of unwellness, dyspnea, and mild respiratory distress. She reported these symptoms had become more and more severe in the last 24 hours and were accompanied by acute chest pain and progressive shortness of breath.

On clinical examination, the patient was hypotensive, had tachypnea and tachycardia, and was hypoxic. Cardiac auscultation detected a systolic murmur in the apex, and auscultation of the lungs revealed crackles and rales, especially at the bases of the lungs. The remainder of her clinical examination was unremarkable.  She had sinus tachycardia on an electrocardiogram. A chest X-ray showed a left atrial enlargement along with some patchy opacities in the middle and lower zones of the lungs, along with Kerley B lines suggestive of pulmonary edema.

With these findings, and after adequate resuscitation, a contrast-enhanced computed tomography (CT) scan detected a filling defect in the left atrium suggestive of a large intra-cardiac mass with a thick and hyper-enhanced interatrial septum. Bilateral pleural effusions also were evident, (Figure 1A) hence an echocardiogram was requested and it confirmed the presence of a 30 x 29 x 40 mm lobulated highly mobile mass in the left atrium. 

After a cardiothoracic consultation, cardiac magnetic resonance imaging (MRI) was performed. The findings showed the presence of a 58 x 45 x 6 mm well-circumscribed hyperemic mass on the anterior leaflet of the mitral valve and a second 10 x 10 x 6 mm smaller mass firmly adhered to the posterior leaflet of the mitral valve. 

The patient, who was hypotensive and hypoxic, was admitted to the hospital for surgical treatment.

Following sternotomy and cardiopulmonary bypass, a right atriotomy was performed using a trans-septal approach. The large left atrial mass was firmly adhered to the endocardium at the level of the anterior leaflet of the mitral valve and the interatrial septum. The mass had a grey and whitish appearance with some bluish necrotic patches, (Figure 1B, 2B, 3B). 

The patient had a complicated postoperative course in the Intensive Care Unit (ICU) and needed inotropic support and vasoactive agents. A postop echocardiogram indicated appropriate left ventricle systolic function, nonetheless, the patient persisted in a hypotensive status that caused refractory shock and ultimately provoked severe organ dysfunction that led to the patient’s death.

Discussion

Primary heart sarcomas are extremely rare malignant neoplasms derived from mesenchymal cells, (1) with an incidence ranging from 0.001% to 0.28% at autopsy. 

Cardiac angiosarcomas (CA) account for one-third of all primary heart sarcomas (4) and usually develop as gray-brown masses with hemorrhagic patches in the right atrium of male patients. The tumors are filled with vascular channels and their cells are positive for CD34 and factor VIII. (5)  Left-sided cardiac angiosarcoma can cause heart failure early in the disease process, but the tumors tend to be more circumscribed, less infiltrative, and associated with better overall survival. (6, 7) Most patients are asymptomatic early in their disease, (2) making the diagnosis even more difficult and worsening its already poor prognosis. (1) The preference of cardiac angiosarcomas for the right heart often leads to a presentation with right-sided congestive heart failure. (2) At later stages, symptoms depend on the structures compromised and range from mild dyspnea on exertion to cardiogenic shock. (8) Cardiac angiosarcomas tend to have a notable intracavitary element, and in some cases may intermittently compromise a cardiac valve, thereby simulating a stenosis or regurgitation. (2, 7)

Our patient presented with acute cardiac failure, pulmonary edema and severe valve dysfunction due to a mass in the left atrium. The tumor had a vascular supply and showed positivity for CD34.

Most patients with cardiac angiosarcoma have metastases, typically to the lung, at diagnosis. (1) Several decades ago, cardiac angiosarcoma was mainly diagnosed postmortem. (1) Now, it can be suspected when cardiomegaly or pleural effusions are seen on chest x-rays (8). Echocardiography is the most useful diagnostic tool, (2) however, CT and MRI can provide useful information on tumor size, invasion and localization. (2, 9) This imaging combination generally provides an excellent anatomic description for preoperative planning. (1, 9)

In our patient, progressive dyspnea was the main symptom and after a prompt evaluation an intracardiac mass was identified as the cause of severe cardiac dysfunction. Because of this finding and the clinical condition of the patient, surgery was planned.

Complete resection of the tumor is the treatment of choice, and is the only therapy currently seen to influence survival. (8) But because of the highly aggressive behavior and a high incidence of systemic metastases with cardiac angiosarcomas, a complete surgical resection is often hampered. (1)  Cardiac angiosarcoma carries a grim prognosis as these tumors are universally fatal with a mean survival time of several months after initial presentation even after successful surgery. (2) Chemotherapy is recommended after surgery, even when clear surgical margins are obtained because of the high probability of missed microscopic disease. (1, 2)

High clinical suspicion together with an appropriate history, a thorough physical examination, and precise complementary tests are vital for timely diagnosis and proper treatment.

Authors and Affiliations
Santiago A. Endara: Department of General Surgery, Division of Cardiothoracic Surgery, Hospital Metropolitano, Quito, Ecuador, MD
Gerardo A. Dávalos: Department of General Surgery, Division of Cardiothoracic Surgery, Hospital Metropolitano, Quito, Ecuador, MD
Patricia M. Pontón: Hospital Metropolitano, Quito, Ecuador. Department of Internal Medicine Division of Pathology, MD
Gabriel A. Molina: Pontificia Universidad Católica del Ecuador (PUCE), Quito, Ecuador. PGY4 General Surgery Resident, MD
Daniel L. Mogrovejo: Pontificia Universidad Católica del Ecuador (PUCE), Quito, Ecuador. PGY1 General Surgery Resident, MD
Corresponding Author Info:
Santiago A. Endara, Hospital Metropolitano, Av. Mariana de Jesus Oe 7/47 y Conclina, Edificio Diagnostico 2000 tercer piso 3/3, Quito, Ecuador, + 593 9 98416157
Email: [email protected]

Abstract

Primary heart sarcomas are rare and represent 20% of all primary cardiac tumors. Symptoms depend on which chambers and cardiac structures are involved. Angiosarcoma is one of the most common and the most aggressive types of primary heart sarcomas. Typically, these tumors are found in the right atrium, however, cardiac angiosarcomas may involve any part of the heart. Most of these tumors are diagnosed in advanced stages and the patient prognosis is poor. Most tumors are diagnosed using echocardiography. Computed tomography (CT) and magnetic resonance imaging (MRI) provide useful information on tumor size and location for planning surgery, which is the only treatment shown to increase survival.  We present the case of a 69-year-old woman who presented to the emergency department with hypotension, dyspnea and progressive shortness of breath. After adequate resuscitation, a cardiac mass was identified and surgery was successfully performed. Pathology confirmed a grade 2 primary heart angiosarcoma. Following surgery, the patient was admitted to the intensive care unit and later died secondary to multi-organ system failure.

Introduction

Primary heart angiosarcoma is an aggressive and usually fatal cardiac neoplasm (1). Angiosarcomas can originate at any location in the heart (2, 3), but these tumors typically reside in the right atrium and frequently cause nonspecific symptoms such as dyspnea, cough, heart failure, and arrhythmias. (2) Surgery followed by chemotherapy is the typical approach to these tumors. (4)

We present the case of a 69-year-old woman who presented to the emergency department with hypotension and severe dyspnea.

Case Report

The patient was a 69-year-old woman with a medical history of diabetes. A week before seeking care in the emergency department, she experienced a general feeling of unwellness, dyspnea, and mild respiratory distress. She reported these symptoms had become more and more severe in the last 24 hours and were accompanied by acute chest pain and progressive shortness of breath.

On clinical examination, the patient was hypotensive, had tachypnea and tachycardia, and was hypoxic. Cardiac auscultation detected a systolic murmur in the apex, and auscultation of the lungs revealed crackles and rales, especially at the bases of the lungs. The remainder of her clinical examination was unremarkable.  She had sinus tachycardia on an electrocardiogram. A chest X-ray showed a left atrial enlargement along with some patchy opacities in the middle and lower zones of the lungs, along with Kerley B lines suggestive of pulmonary edema.

With these findings, and after adequate resuscitation, a contrast-enhanced computed tomography (CT) scan detected a filling defect in the left atrium suggestive of a large intra-cardiac mass with a thick and hyper-enhanced interatrial septum. Bilateral pleural effusions also were evident, (Figure 1A) hence an echocardiogram was requested and it confirmed the presence of a 30 x 29 x 40 mm lobulated highly mobile mass in the left atrium. 

After a cardiothoracic consultation, cardiac magnetic resonance imaging (MRI) was performed. The findings showed the presence of a 58 x 45 x 6 mm well-circumscribed hyperemic mass on the anterior leaflet of the mitral valve and a second 10 x 10 x 6 mm smaller mass firmly adhered to the posterior leaflet of the mitral valve. 

The patient, who was hypotensive and hypoxic, was admitted to the hospital for surgical treatment.

Following sternotomy and cardiopulmonary bypass, a right atriotomy was performed using a trans-septal approach. The large left atrial mass was firmly adhered to the endocardium at the level of the anterior leaflet of the mitral valve and the interatrial septum. The mass had a grey and whitish appearance with some bluish necrotic patches, (Figure 1B, 2B, 3B). 

The patient had a complicated postoperative course in the Intensive Care Unit (ICU) and needed inotropic support and vasoactive agents. A postop echocardiogram indicated appropriate left ventricle systolic function, nonetheless, the patient persisted in a hypotensive status that caused refractory shock and ultimately provoked severe organ dysfunction that led to the patient’s death.

Discussion

Primary heart sarcomas are extremely rare malignant neoplasms derived from mesenchymal cells, (1) with an incidence ranging from 0.001% to 0.28% at autopsy. 

Cardiac angiosarcomas (CA) account for one-third of all primary heart sarcomas (4) and usually develop as gray-brown masses with hemorrhagic patches in the right atrium of male patients. The tumors are filled with vascular channels and their cells are positive for CD34 and factor VIII. (5)  Left-sided cardiac angiosarcoma can cause heart failure early in the disease process, but the tumors tend to be more circumscribed, less infiltrative, and associated with better overall survival. (6, 7) Most patients are asymptomatic early in their disease, (2) making the diagnosis even more difficult and worsening its already poor prognosis. (1) The preference of cardiac angiosarcomas for the right heart often leads to a presentation with right-sided congestive heart failure. (2) At later stages, symptoms depend on the structures compromised and range from mild dyspnea on exertion to cardiogenic shock. (8) Cardiac angiosarcomas tend to have a notable intracavitary element, and in some cases may intermittently compromise a cardiac valve, thereby simulating a stenosis or regurgitation. (2, 7)

Our patient presented with acute cardiac failure, pulmonary edema and severe valve dysfunction due to a mass in the left atrium. The tumor had a vascular supply and showed positivity for CD34.

Most patients with cardiac angiosarcoma have metastases, typically to the lung, at diagnosis. (1) Several decades ago, cardiac angiosarcoma was mainly diagnosed postmortem. (1) Now, it can be suspected when cardiomegaly or pleural effusions are seen on chest x-rays (8). Echocardiography is the most useful diagnostic tool, (2) however, CT and MRI can provide useful information on tumor size, invasion and localization. (2, 9) This imaging combination generally provides an excellent anatomic description for preoperative planning. (1, 9)

In our patient, progressive dyspnea was the main symptom and after a prompt evaluation an intracardiac mass was identified as the cause of severe cardiac dysfunction. Because of this finding and the clinical condition of the patient, surgery was planned.

Complete resection of the tumor is the treatment of choice, and is the only therapy currently seen to influence survival. (8) But because of the highly aggressive behavior and a high incidence of systemic metastases with cardiac angiosarcomas, a complete surgical resection is often hampered. (1)  Cardiac angiosarcoma carries a grim prognosis as these tumors are universally fatal with a mean survival time of several months after initial presentation even after successful surgery. (2) Chemotherapy is recommended after surgery, even when clear surgical margins are obtained because of the high probability of missed microscopic disease. (1, 2)

High clinical suspicion together with an appropriate history, a thorough physical examination, and precise complementary tests are vital for timely diagnosis and proper treatment.

Authors and Affiliations
Santiago A. Endara: Department of General Surgery, Division of Cardiothoracic Surgery, Hospital Metropolitano, Quito, Ecuador, MD
Gerardo A. Dávalos: Department of General Surgery, Division of Cardiothoracic Surgery, Hospital Metropolitano, Quito, Ecuador, MD
Patricia M. Pontón: Hospital Metropolitano, Quito, Ecuador. Department of Internal Medicine Division of Pathology, MD
Gabriel A. Molina: Pontificia Universidad Católica del Ecuador (PUCE), Quito, Ecuador. PGY4 General Surgery Resident, MD
Daniel L. Mogrovejo: Pontificia Universidad Católica del Ecuador (PUCE), Quito, Ecuador. PGY1 General Surgery Resident, MD
Corresponding Author Info:
Santiago A. Endara, Hospital Metropolitano, Av. Mariana de Jesus Oe 7/47 y Conclina, Edificio Diagnostico 2000 tercer piso 3/3, Quito, Ecuador, + 593 9 98416157
Email: [email protected]

Abstract

Primary heart sarcomas are rare and represent 20% of all primary cardiac tumors. Symptoms depend on which chambers and cardiac structures are involved. Angiosarcoma is one of the most common and the most aggressive types of primary heart sarcomas. Typically, these tumors are found in the right atrium, however, cardiac angiosarcomas may involve any part of the heart. Most of these tumors are diagnosed in advanced stages and the patient prognosis is poor. Most tumors are diagnosed using echocardiography. Computed tomography (CT) and magnetic resonance imaging (MRI) provide useful information on tumor size and location for planning surgery, which is the only treatment shown to increase survival.  We present the case of a 69-year-old woman who presented to the emergency department with hypotension, dyspnea and progressive shortness of breath. After adequate resuscitation, a cardiac mass was identified and surgery was successfully performed. Pathology confirmed a grade 2 primary heart angiosarcoma. Following surgery, the patient was admitted to the intensive care unit and later died secondary to multi-organ system failure.

Introduction

Primary heart angiosarcoma is an aggressive and usually fatal cardiac neoplasm (1). Angiosarcomas can originate at any location in the heart (2, 3), but these tumors typically reside in the right atrium and frequently cause nonspecific symptoms such as dyspnea, cough, heart failure, and arrhythmias. (2) Surgery followed by chemotherapy is the typical approach to these tumors. (4)

We present the case of a 69-year-old woman who presented to the emergency department with hypotension and severe dyspnea.

Case Report

The patient was a 69-year-old woman with a medical history of diabetes. A week before seeking care in the emergency department, she experienced a general feeling of unwellness, dyspnea, and mild respiratory distress. She reported these symptoms had become more and more severe in the last 24 hours and were accompanied by acute chest pain and progressive shortness of breath.

On clinical examination, the patient was hypotensive, had tachypnea and tachycardia, and was hypoxic. Cardiac auscultation detected a systolic murmur in the apex, and auscultation of the lungs revealed crackles and rales, especially at the bases of the lungs. The remainder of her clinical examination was unremarkable.  She had sinus tachycardia on an electrocardiogram. A chest X-ray showed a left atrial enlargement along with some patchy opacities in the middle and lower zones of the lungs, along with Kerley B lines suggestive of pulmonary edema.

With these findings, and after adequate resuscitation, a contrast-enhanced computed tomography (CT) scan detected a filling defect in the left atrium suggestive of a large intra-cardiac mass with a thick and hyper-enhanced interatrial septum. Bilateral pleural effusions also were evident, (Figure 1A) hence an echocardiogram was requested and it confirmed the presence of a 30 x 29 x 40 mm lobulated highly mobile mass in the left atrium. 

After a cardiothoracic consultation, cardiac magnetic resonance imaging (MRI) was performed. The findings showed the presence of a 58 x 45 x 6 mm well-circumscribed hyperemic mass on the anterior leaflet of the mitral valve and a second 10 x 10 x 6 mm smaller mass firmly adhered to the posterior leaflet of the mitral valve. 

The patient, who was hypotensive and hypoxic, was admitted to the hospital for surgical treatment.

Following sternotomy and cardiopulmonary bypass, a right atriotomy was performed using a trans-septal approach. The large left atrial mass was firmly adhered to the endocardium at the level of the anterior leaflet of the mitral valve and the interatrial septum. The mass had a grey and whitish appearance with some bluish necrotic patches, (Figure 1B, 2B, 3B). 

The patient had a complicated postoperative course in the Intensive Care Unit (ICU) and needed inotropic support and vasoactive agents. A postop echocardiogram indicated appropriate left ventricle systolic function, nonetheless, the patient persisted in a hypotensive status that caused refractory shock and ultimately provoked severe organ dysfunction that led to the patient’s death.

Discussion

Primary heart sarcomas are extremely rare malignant neoplasms derived from mesenchymal cells, (1) with an incidence ranging from 0.001% to 0.28% at autopsy. 

Cardiac angiosarcomas (CA) account for one-third of all primary heart sarcomas (4) and usually develop as gray-brown masses with hemorrhagic patches in the right atrium of male patients. The tumors are filled with vascular channels and their cells are positive for CD34 and factor VIII. (5)  Left-sided cardiac angiosarcoma can cause heart failure early in the disease process, but the tumors tend to be more circumscribed, less infiltrative, and associated with better overall survival. (6, 7) Most patients are asymptomatic early in their disease, (2) making the diagnosis even more difficult and worsening its already poor prognosis. (1) The preference of cardiac angiosarcomas for the right heart often leads to a presentation with right-sided congestive heart failure. (2) At later stages, symptoms depend on the structures compromised and range from mild dyspnea on exertion to cardiogenic shock. (8) Cardiac angiosarcomas tend to have a notable intracavitary element, and in some cases may intermittently compromise a cardiac valve, thereby simulating a stenosis or regurgitation. (2, 7)

Our patient presented with acute cardiac failure, pulmonary edema and severe valve dysfunction due to a mass in the left atrium. The tumor had a vascular supply and showed positivity for CD34.

Most patients with cardiac angiosarcoma have metastases, typically to the lung, at diagnosis. (1) Several decades ago, cardiac angiosarcoma was mainly diagnosed postmortem. (1) Now, it can be suspected when cardiomegaly or pleural effusions are seen on chest x-rays (8). Echocardiography is the most useful diagnostic tool, (2) however, CT and MRI can provide useful information on tumor size, invasion and localization. (2, 9) This imaging combination generally provides an excellent anatomic description for preoperative planning. (1, 9)

In our patient, progressive dyspnea was the main symptom and after a prompt evaluation an intracardiac mass was identified as the cause of severe cardiac dysfunction. Because of this finding and the clinical condition of the patient, surgery was planned.

Complete resection of the tumor is the treatment of choice, and is the only therapy currently seen to influence survival. (8) But because of the highly aggressive behavior and a high incidence of systemic metastases with cardiac angiosarcomas, a complete surgical resection is often hampered. (1)  Cardiac angiosarcoma carries a grim prognosis as these tumors are universally fatal with a mean survival time of several months after initial presentation even after successful surgery. (2) Chemotherapy is recommended after surgery, even when clear surgical margins are obtained because of the high probability of missed microscopic disease. (1, 2)

High clinical suspicion together with an appropriate history, a thorough physical examination, and precise complementary tests are vital for timely diagnosis and proper treatment.

Authors and Affiliations
Santiago A. Endara: Department of General Surgery, Division of Cardiothoracic Surgery, Hospital Metropolitano, Quito, Ecuador, MD
Gerardo A. Dávalos: Department of General Surgery, Division of Cardiothoracic Surgery, Hospital Metropolitano, Quito, Ecuador, MD
Patricia M. Pontón: Hospital Metropolitano, Quito, Ecuador. Department of Internal Medicine Division of Pathology, MD
Gabriel A. Molina: Pontificia Universidad Católica del Ecuador (PUCE), Quito, Ecuador. PGY4 General Surgery Resident, MD
Daniel L. Mogrovejo: Pontificia Universidad Católica del Ecuador (PUCE), Quito, Ecuador. PGY1 General Surgery Resident, MD
Corresponding Author Info:
Santiago A. Endara, Hospital Metropolitano, Av. Mariana de Jesus Oe 7/47 y Conclina, Edificio Diagnostico 2000 tercer piso 3/3, Quito, Ecuador, + 593 9 98416157
Email: [email protected]