Image Quizzes

This patient's findings are consistent with a diagnosis of malignant mantle cell lymphoma (MCL).

MCL is a rare and aggressive form of non-Hodgkin lymphoma that accounts for approximately 5%-7% of all lymphomas. MCL has a characteristic immunophenotype (ie, CD5+, CD10−, Bcl-2+, Bcl-6−, CD20+), with the t(11;14)(q13;q32) chromosomal translocation, and expression of cyclin D1. The median age at diagnosis is between 60 and 70 years. Approximately 70% of all cases occur in men. 

The clinical presentation of MCL can vary. Patients may have asymptomatic monoclonal MCL type lymphocytosis or nonbulky nodal/extra nodal disease with minimal symptoms, or they may present with significant symptoms, progressive generalized lymphadenopathy, cytopenia, splenomegaly, and extranodal disease, including gastrointestinal involvement (lymphomatous polyposis), kidney involvement, involvement of other organs, or, rarely, central nervous system involvement. Disease involving multiple lymph nodes and other sites of the body is seen in most patients. Approximately 70% of patients present with stage IV disease requiring systemic treatment.

According to 2022 guidelines from the National Comprehensive Cancer Network (NCCN), essential components in the workup for MCL include:

•    Physical examination, with attention to node-bearing areas, including Waldeyer ring, and to size of liver and spleen
•    Assessment of performance status and B symptoms (ie, fever > 100.4°F [may be sporadic], drenching night sweats, unintentional weight loss of > 10% of body weight over 6 months or less)
•    CBC with differential
•    Comprehensive metabolic panel
•    Serum lactate dehydrogenase (LDH) level (an important prognostic marker)
•    PET/CT scan (including neck)
•    Hepatitis B testing if treatment with rituximab is being contemplated
•    Echocardiogram or multigated acquisition (MUGA) scan if anthracycline or anthracenedione-based regimen is indicated
•    Pregnancy testing in women of childbearing age (if chemotherapy or radiation therapy is planned) 

Additional testing may be indicated in specific circumstances, such as colonoscopy/endoscopy. 

MCL remains challenging to treat. While 50%-90% of patients with MCL respond to combination chemotherapy, only 30% achieve a complete response. Median time to treatment failure is < 18 months. 

When selecting systemic treatment for patients with MCL, clinicians should consider the availability of clinical trials for subsets of patients, eligibility for stem cell transplant (SCT), high-risk status (ie, blastoid MCL, high Ki-67% > 30%, or central nervous system involvement), age, and performance status. The addition of radiation to chemotherapy may be beneficial for patients with limited-stage, nonbulky disease, although this has not been confirmed in large, randomized studies. Outside of clinical trials, the usual approach for frontline treatment of MCL is chemoimmunotherapy with/without autologous SCT and with/without maintenance therapy.

Available options for primary MCL therapy in patients who require systemic therapy include: 

•    Single alkylating agents
•    CVP (cyclophosphamide, vincristine, prednisone)
•    CHOP (cyclophosphamide, doxorubicin [hydroxydaunorubicin], vincristine [Oncovin], prednisone)
•    Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) with or without rituximab
•    R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)
•    Lenalidomide plus rituximab
•    Hyper-CVAD with autologous SCT

Options for relapsed or refractory MCL include:

•    R-hyper-CVAD
•    Hyper-CVAD with or without rituximab followed by autologous SCT
•    Nucleoside analogues and combinations
•    Salvage chemotherapy combinations followed by autologous SCT
•    Bortezomib 
•    Lenalidomide 
•    Ibrutinib 
•    Radioimmunotherapy
•    Rituximab
•    Rituximab and thalidomide combination
•    Acalabrutinib 
•    High-dose chemotherapy with autologous bone marrow or SCT
•    Brexucabtagene autoleucel 

Timothy J. Voorhees, MD, MSCR, Assistant Professor of Internal Medicine - Clinical, Division of Hematology, The Ohio State University James Comprehensive Cancer Center, Columbus, OH.

Timothy J. Voorhees, MD, MSCR, has disclosed the following relevant financial relationships:
Received research grant from: AstraZeneca; Morphosys; Incyte; Recordati.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's findings are consistent with a diagnosis of malignant mantle cell lymphoma (MCL).

MCL is a rare and aggressive form of non-Hodgkin lymphoma that accounts for approximately 5%-7% of all lymphomas. MCL has a characteristic immunophenotype (ie, CD5+, CD10−, Bcl-2+, Bcl-6−, CD20+), with the t(11;14)(q13;q32) chromosomal translocation, and expression of cyclin D1. The median age at diagnosis is between 60 and 70 years. Approximately 70% of all cases occur in men. 

The clinical presentation of MCL can vary. Patients may have asymptomatic monoclonal MCL type lymphocytosis or nonbulky nodal/extra nodal disease with minimal symptoms, or they may present with significant symptoms, progressive generalized lymphadenopathy, cytopenia, splenomegaly, and extranodal disease, including gastrointestinal involvement (lymphomatous polyposis), kidney involvement, involvement of other organs, or, rarely, central nervous system involvement. Disease involving multiple lymph nodes and other sites of the body is seen in most patients. Approximately 70% of patients present with stage IV disease requiring systemic treatment.

According to 2022 guidelines from the National Comprehensive Cancer Network (NCCN), essential components in the workup for MCL include:

•    Physical examination, with attention to node-bearing areas, including Waldeyer ring, and to size of liver and spleen
•    Assessment of performance status and B symptoms (ie, fever > 100.4°F [may be sporadic], drenching night sweats, unintentional weight loss of > 10% of body weight over 6 months or less)
•    CBC with differential
•    Comprehensive metabolic panel
•    Serum lactate dehydrogenase (LDH) level (an important prognostic marker)
•    PET/CT scan (including neck)
•    Hepatitis B testing if treatment with rituximab is being contemplated
•    Echocardiogram or multigated acquisition (MUGA) scan if anthracycline or anthracenedione-based regimen is indicated
•    Pregnancy testing in women of childbearing age (if chemotherapy or radiation therapy is planned) 

Additional testing may be indicated in specific circumstances, such as colonoscopy/endoscopy. 

MCL remains challenging to treat. While 50%-90% of patients with MCL respond to combination chemotherapy, only 30% achieve a complete response. Median time to treatment failure is < 18 months. 

When selecting systemic treatment for patients with MCL, clinicians should consider the availability of clinical trials for subsets of patients, eligibility for stem cell transplant (SCT), high-risk status (ie, blastoid MCL, high Ki-67% > 30%, or central nervous system involvement), age, and performance status. The addition of radiation to chemotherapy may be beneficial for patients with limited-stage, nonbulky disease, although this has not been confirmed in large, randomized studies. Outside of clinical trials, the usual approach for frontline treatment of MCL is chemoimmunotherapy with/without autologous SCT and with/without maintenance therapy.

Available options for primary MCL therapy in patients who require systemic therapy include: 

•    Single alkylating agents
•    CVP (cyclophosphamide, vincristine, prednisone)
•    CHOP (cyclophosphamide, doxorubicin [hydroxydaunorubicin], vincristine [Oncovin], prednisone)
•    Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) with or without rituximab
•    R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)
•    Lenalidomide plus rituximab
•    Hyper-CVAD with autologous SCT

Options for relapsed or refractory MCL include:

•    R-hyper-CVAD
•    Hyper-CVAD with or without rituximab followed by autologous SCT
•    Nucleoside analogues and combinations
•    Salvage chemotherapy combinations followed by autologous SCT
•    Bortezomib 
•    Lenalidomide 
•    Ibrutinib 
•    Radioimmunotherapy
•    Rituximab
•    Rituximab and thalidomide combination
•    Acalabrutinib 
•    High-dose chemotherapy with autologous bone marrow or SCT
•    Brexucabtagene autoleucel 

Timothy J. Voorhees, MD, MSCR, Assistant Professor of Internal Medicine - Clinical, Division of Hematology, The Ohio State University James Comprehensive Cancer Center, Columbus, OH.

Timothy J. Voorhees, MD, MSCR, has disclosed the following relevant financial relationships:
Received research grant from: AstraZeneca; Morphosys; Incyte; Recordati.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's findings are consistent with a diagnosis of malignant mantle cell lymphoma (MCL).

MCL is a rare and aggressive form of non-Hodgkin lymphoma that accounts for approximately 5%-7% of all lymphomas. MCL has a characteristic immunophenotype (ie, CD5+, CD10−, Bcl-2+, Bcl-6−, CD20+), with the t(11;14)(q13;q32) chromosomal translocation, and expression of cyclin D1. The median age at diagnosis is between 60 and 70 years. Approximately 70% of all cases occur in men. 

The clinical presentation of MCL can vary. Patients may have asymptomatic monoclonal MCL type lymphocytosis or nonbulky nodal/extra nodal disease with minimal symptoms, or they may present with significant symptoms, progressive generalized lymphadenopathy, cytopenia, splenomegaly, and extranodal disease, including gastrointestinal involvement (lymphomatous polyposis), kidney involvement, involvement of other organs, or, rarely, central nervous system involvement. Disease involving multiple lymph nodes and other sites of the body is seen in most patients. Approximately 70% of patients present with stage IV disease requiring systemic treatment.

According to 2022 guidelines from the National Comprehensive Cancer Network (NCCN), essential components in the workup for MCL include:

•    Physical examination, with attention to node-bearing areas, including Waldeyer ring, and to size of liver and spleen
•    Assessment of performance status and B symptoms (ie, fever > 100.4°F [may be sporadic], drenching night sweats, unintentional weight loss of > 10% of body weight over 6 months or less)
•    CBC with differential
•    Comprehensive metabolic panel
•    Serum lactate dehydrogenase (LDH) level (an important prognostic marker)
•    PET/CT scan (including neck)
•    Hepatitis B testing if treatment with rituximab is being contemplated
•    Echocardiogram or multigated acquisition (MUGA) scan if anthracycline or anthracenedione-based regimen is indicated
•    Pregnancy testing in women of childbearing age (if chemotherapy or radiation therapy is planned) 

Additional testing may be indicated in specific circumstances, such as colonoscopy/endoscopy. 

MCL remains challenging to treat. While 50%-90% of patients with MCL respond to combination chemotherapy, only 30% achieve a complete response. Median time to treatment failure is < 18 months. 

When selecting systemic treatment for patients with MCL, clinicians should consider the availability of clinical trials for subsets of patients, eligibility for stem cell transplant (SCT), high-risk status (ie, blastoid MCL, high Ki-67% > 30%, or central nervous system involvement), age, and performance status. The addition of radiation to chemotherapy may be beneficial for patients with limited-stage, nonbulky disease, although this has not been confirmed in large, randomized studies. Outside of clinical trials, the usual approach for frontline treatment of MCL is chemoimmunotherapy with/without autologous SCT and with/without maintenance therapy.

Available options for primary MCL therapy in patients who require systemic therapy include: 

•    Single alkylating agents
•    CVP (cyclophosphamide, vincristine, prednisone)
•    CHOP (cyclophosphamide, doxorubicin [hydroxydaunorubicin], vincristine [Oncovin], prednisone)
•    Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) with or without rituximab
•    R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)
•    Lenalidomide plus rituximab
•    Hyper-CVAD with autologous SCT

Options for relapsed or refractory MCL include:

•    R-hyper-CVAD
•    Hyper-CVAD with or without rituximab followed by autologous SCT
•    Nucleoside analogues and combinations
•    Salvage chemotherapy combinations followed by autologous SCT
•    Bortezomib 
•    Lenalidomide 
•    Ibrutinib 
•    Radioimmunotherapy
•    Rituximab
•    Rituximab and thalidomide combination
•    Acalabrutinib 
•    High-dose chemotherapy with autologous bone marrow or SCT
•    Brexucabtagene autoleucel 

Timothy J. Voorhees, MD, MSCR, Assistant Professor of Internal Medicine - Clinical, Division of Hematology, The Ohio State University James Comprehensive Cancer Center, Columbus, OH.

Timothy J. Voorhees, MD, MSCR, has disclosed the following relevant financial relationships:
Received research grant from: AstraZeneca; Morphosys; Incyte; Recordati.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's symptoms are consistent with a diagnosis of blepharitis.

Blepharitis is an inflammatory disorder of the eyelids that is frequently associated with bacterial colonization of the eyelid. Anatomically, it can be categorized as anterior blepharitis or posterior blepharitis. Anterior blepharitis refers to inflammation primarily positioned around the skin, eyelashes, and lash follicles and is usually further divided into staphylococcal and seborrheic variants. Posterior blepharitis involves the meibomian gland orifices, meibomian glands, tarsal plate, and blepharo-conjunctival junction. 

Blepharitis can be acute or chronic. It is frequently associated with systemic diseases, such as rosacea, atopy, and seborrheic dermatitis, as well as ocular diseases, such as dry eye syndromes, chalazion, trichiasis, ectropion and entropion, infectious or other inflammatory conjunctivitis, and keratitis. Moreover, high rates of blepharitis have been reported in patients treated with dupilumab for atopic dermatitis. 

Eye irritation, itching, erythema of the lids, flaking of the lid margins, and/or changes in the eyelashes are common presenting symptoms in patients with blepharitis. Other symptoms may include:
•    Burning
•    Watering
•    Foreign-body sensation
•    Crusting and mattering of the lashes and medial canthus
•    Red lids
•    Red eyes
•    Photophobia
•    Pain
•    Decreased vision
•    Visual fluctuations
•    Heat, cold, alcohol, and spicy-food intolerance

The differential diagnosis for blepharitis includes bacterial keratitis, which is a serious ocular disorder that can lead to vision loss if not properly treated. Bacterial keratitis progresses rapidly and can result in corneal destruction within 24-48 hours with some particularly virulent bacteria. Patients with bacterial keratitis typically report rapid onset of pain, photophobia, and decreased vision.

Ocular rosacea should also be considered in the differential diagnosis of blepharitis, and the two conditions can co-occur. Patients with ocular rosacea may experience facial symptoms (eg, recurrent flushing episodes, persistent and/or recurrent midfacial erythema, papular and pustular lesions) in addition to ocular symptoms, which can range from minor irritation, foreign-body sensation, and blurry vision to severe ocular surface disruption and inflammatory keratitis.

Bacterial conjunctivitis involves inflammation of the bulbar and/or palpebral conjunctiva, whereas blepharitis involves inflammation of the eyelids only. Other conditions to consider in the diagnosis of blepharitis can be found here. 

Given the unprecedented efficacy seen in clinical trials, dupilumab is emerging as a first-line therapeutic for moderate to severe atopic dermatitis. However, clinicians should be alert to ocular complications among their patients with atopic dermatitis who are being treated with dupilumab. In some patients, this may be because of preexisting meibomian gland disease and ocular surface disease. After a diagnosis of ocular complications, the continued use of dupilumab should be jointly evaluated by the ophthalmologist and dermatologist or allergist on the basis of the ocular risk vs systemic benefit. Treatment for blepharitis typically includes strict eyelid hygiene and topical antibiotic ointment; oral antibiotics can be beneficial for refractory disease.

William D. James, MD, Professor, Department of Dermatology, University of Pennsylvania, Philadelphia.

Disclosure: William D. James, MD, has disclosed the following relevant financial relationships:
Received income in an amount equal to or greater than $250 from: Elsevier.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's symptoms are consistent with a diagnosis of blepharitis.

Blepharitis is an inflammatory disorder of the eyelids that is frequently associated with bacterial colonization of the eyelid. Anatomically, it can be categorized as anterior blepharitis or posterior blepharitis. Anterior blepharitis refers to inflammation primarily positioned around the skin, eyelashes, and lash follicles and is usually further divided into staphylococcal and seborrheic variants. Posterior blepharitis involves the meibomian gland orifices, meibomian glands, tarsal plate, and blepharo-conjunctival junction. 

Blepharitis can be acute or chronic. It is frequently associated with systemic diseases, such as rosacea, atopy, and seborrheic dermatitis, as well as ocular diseases, such as dry eye syndromes, chalazion, trichiasis, ectropion and entropion, infectious or other inflammatory conjunctivitis, and keratitis. Moreover, high rates of blepharitis have been reported in patients treated with dupilumab for atopic dermatitis. 

Eye irritation, itching, erythema of the lids, flaking of the lid margins, and/or changes in the eyelashes are common presenting symptoms in patients with blepharitis. Other symptoms may include:
•    Burning
•    Watering
•    Foreign-body sensation
•    Crusting and mattering of the lashes and medial canthus
•    Red lids
•    Red eyes
•    Photophobia
•    Pain
•    Decreased vision
•    Visual fluctuations
•    Heat, cold, alcohol, and spicy-food intolerance

The differential diagnosis for blepharitis includes bacterial keratitis, which is a serious ocular disorder that can lead to vision loss if not properly treated. Bacterial keratitis progresses rapidly and can result in corneal destruction within 24-48 hours with some particularly virulent bacteria. Patients with bacterial keratitis typically report rapid onset of pain, photophobia, and decreased vision.

Ocular rosacea should also be considered in the differential diagnosis of blepharitis, and the two conditions can co-occur. Patients with ocular rosacea may experience facial symptoms (eg, recurrent flushing episodes, persistent and/or recurrent midfacial erythema, papular and pustular lesions) in addition to ocular symptoms, which can range from minor irritation, foreign-body sensation, and blurry vision to severe ocular surface disruption and inflammatory keratitis.

Bacterial conjunctivitis involves inflammation of the bulbar and/or palpebral conjunctiva, whereas blepharitis involves inflammation of the eyelids only. Other conditions to consider in the diagnosis of blepharitis can be found here. 

Given the unprecedented efficacy seen in clinical trials, dupilumab is emerging as a first-line therapeutic for moderate to severe atopic dermatitis. However, clinicians should be alert to ocular complications among their patients with atopic dermatitis who are being treated with dupilumab. In some patients, this may be because of preexisting meibomian gland disease and ocular surface disease. After a diagnosis of ocular complications, the continued use of dupilumab should be jointly evaluated by the ophthalmologist and dermatologist or allergist on the basis of the ocular risk vs systemic benefit. Treatment for blepharitis typically includes strict eyelid hygiene and topical antibiotic ointment; oral antibiotics can be beneficial for refractory disease.

William D. James, MD, Professor, Department of Dermatology, University of Pennsylvania, Philadelphia.

Disclosure: William D. James, MD, has disclosed the following relevant financial relationships:
Received income in an amount equal to or greater than $250 from: Elsevier.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's symptoms are consistent with a diagnosis of blepharitis.

Blepharitis is an inflammatory disorder of the eyelids that is frequently associated with bacterial colonization of the eyelid. Anatomically, it can be categorized as anterior blepharitis or posterior blepharitis. Anterior blepharitis refers to inflammation primarily positioned around the skin, eyelashes, and lash follicles and is usually further divided into staphylococcal and seborrheic variants. Posterior blepharitis involves the meibomian gland orifices, meibomian glands, tarsal plate, and blepharo-conjunctival junction. 

Blepharitis can be acute or chronic. It is frequently associated with systemic diseases, such as rosacea, atopy, and seborrheic dermatitis, as well as ocular diseases, such as dry eye syndromes, chalazion, trichiasis, ectropion and entropion, infectious or other inflammatory conjunctivitis, and keratitis. Moreover, high rates of blepharitis have been reported in patients treated with dupilumab for atopic dermatitis. 

Eye irritation, itching, erythema of the lids, flaking of the lid margins, and/or changes in the eyelashes are common presenting symptoms in patients with blepharitis. Other symptoms may include:
•    Burning
•    Watering
•    Foreign-body sensation
•    Crusting and mattering of the lashes and medial canthus
•    Red lids
•    Red eyes
•    Photophobia
•    Pain
•    Decreased vision
•    Visual fluctuations
•    Heat, cold, alcohol, and spicy-food intolerance

The differential diagnosis for blepharitis includes bacterial keratitis, which is a serious ocular disorder that can lead to vision loss if not properly treated. Bacterial keratitis progresses rapidly and can result in corneal destruction within 24-48 hours with some particularly virulent bacteria. Patients with bacterial keratitis typically report rapid onset of pain, photophobia, and decreased vision.

Ocular rosacea should also be considered in the differential diagnosis of blepharitis, and the two conditions can co-occur. Patients with ocular rosacea may experience facial symptoms (eg, recurrent flushing episodes, persistent and/or recurrent midfacial erythema, papular and pustular lesions) in addition to ocular symptoms, which can range from minor irritation, foreign-body sensation, and blurry vision to severe ocular surface disruption and inflammatory keratitis.

Bacterial conjunctivitis involves inflammation of the bulbar and/or palpebral conjunctiva, whereas blepharitis involves inflammation of the eyelids only. Other conditions to consider in the diagnosis of blepharitis can be found here. 

Given the unprecedented efficacy seen in clinical trials, dupilumab is emerging as a first-line therapeutic for moderate to severe atopic dermatitis. However, clinicians should be alert to ocular complications among their patients with atopic dermatitis who are being treated with dupilumab. In some patients, this may be because of preexisting meibomian gland disease and ocular surface disease. After a diagnosis of ocular complications, the continued use of dupilumab should be jointly evaluated by the ophthalmologist and dermatologist or allergist on the basis of the ocular risk vs systemic benefit. Treatment for blepharitis typically includes strict eyelid hygiene and topical antibiotic ointment; oral antibiotics can be beneficial for refractory disease.

William D. James, MD, Professor, Department of Dermatology, University of Pennsylvania, Philadelphia.

Disclosure: William D. James, MD, has disclosed the following relevant financial relationships:
Received income in an amount equal to or greater than $250 from: Elsevier.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's findings are consistent with a diagnosis of psoriatic enthesitis.

Enthesitis is a hallmark manifestation of psoriatic arthritis (PsA). Approximately 30% of patients with psoriasis are estimated to be affected by PsA, which belongs to the spondyloarthritis (SpA) family of inflammatory rheumatic diseases. 

An enthesis is an attachment site of ligaments, tendons, and joint capsules to bone and is a key inflammatory target in SpA. It is a complex structure that dissipates biomechanical stress to preserve homeostasis. Entheses are anatomically and functionally integrated with bursa, fibrocartilage, and synovium in a synovial entheseal complex; biomechanical stress in this area may trigger inflammation. Enthesitis is an early manifestation of PsA that has been associated with radiographic peripheral/axial joint damage and severe disease, as well as reduced quality of life.

Enthesitis can be difficult to diagnose in clinical practice. Symptoms include tenderness, soreness, and pain at entheses on palpation, often without overt clinical evidence of inflammation. In contrast, dactylitis, another hallmark manifestation of PsA, can be recognized by swelling of an entire digit that is different from adjacent digits. Fibromyalgia frequently coexists with enthesitis, and it can be difficult to distinguish the two given the anatomic overlap between the tender points of fibromyalgia and many entheseal sites. Long-lasting morning stiffness and a sustained response to a course of steroids is more suggestive of enthesitis, whereas a higher number of somatoform symptoms is more suggestive of fibromyalgia.

Enthesitis is included in the Classification Criteria for Psoriatic Arthritis (CASPAR) as a hallmark of PsA. While it can be diagnosed clinically, imaging studies may be required, particularly in patients in whom symptoms may be difficult to discern. Evidence of enthesitis by conventional radiography includes bone cortex irregularities, erosions, entheseal soft tissue calcifications, and new bone formation; however, entheseal bone changes detected with conventional radiography appear relatively late in the disease process. Ultrasound is highly sensitive for assessing inflammation and can detect various features of enthesitis, such as increased thickness of tendon insertion, hypoechogenicity, erosions, enthesophytes, and subclinical enthesitis in people with PsA. MRI has the advantage of identifying perientheseal inflammation with adjacent bone marrow edema. Fat-suppressed MRI with or without gadolinium enhancement is a highly sensitive method for visualizing active enthesitis and can identify perientheseal inflammation with adjacent bone marrow edema. 

Delayed treatment of PsA can result in irreversible joint damage and reduced quality of life; thus, patients with psoriasis should be closely monitored for early signs of its development, such as enthesitis. A thorough evaluation of the key clinical features of PsA (psoriasis, arthritis, enthesitis, dactylitis, and spondylitis), including evaluation of severity of each feature and impact on physical function and quality of life, is encouraged at each clinical encounter. Because patients may not understand the link between psoriasis and joint pain, specific probing questions can be helpful. Screening questionnaires to detect early signs and symptoms of PsA are available, such as the Psoriasis Epidemiology Screening Tool (PEST), Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire, and Toronto Psoriatic Arthritis Screening (ToPAS) questionnaire. These and many others may be used to help dermatologists detect early signs and symptoms of PsA. Although these questionnaires all have limitations in sensitivity and specificity for the diagnosis of PsA, their use can still improve early diagnosis.

The treatment of PsA focuses on achieving the least amount of disease activity and inflammation possible; optimizing functional status, quality of life, and well-being; and preventing structural damage. Treatment decisions are based on the specific domains affected. Nonsteroidal anti-inflammatory drugs and corticosteroid injections are first-line treatments for enthesitis. Early use of tumor necrosis factor inhibitors (TNF) (adalimumab, certolizumab pegol, etanercept, infliximab, and golimumab) is recommended. Alternative biologic disease-modifying agents are indicated when these TNF inhibitors provide an inadequate response. They include ustekinumab (dual interleukin [IL]-12 and IL-23 inhibitor), secukinumab (IL-17A inhibitor), and apremilast (phosphodiesterase-4 inhibitor) and may be considered for patients with predominantly entheseal manifestations of PsA or dactylitis. Biological disease-modifying agents approved for PsA that have shown efficacy for enthesitis include ixekizumab (which targets IL-17A), abatacept (a T-cell inhibitor), guselkumab (monoclonal antibody), and ustekinumab (monoclonal antibody). Tofacitinib and upadacitinib, both oral Janus kinase inhibitors, may also be considered. 

Herbert S. Diamond, MD, Professor of Medicine (retired), Temple University School of Medicine, University of Pittsburgh; Chairman, Department of Medicine Emeritus, Western Pennsylvania Hospital, Pittsburgh, PA.

Herbert S. Diamond, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's findings are consistent with a diagnosis of psoriatic enthesitis.

Enthesitis is a hallmark manifestation of psoriatic arthritis (PsA). Approximately 30% of patients with psoriasis are estimated to be affected by PsA, which belongs to the spondyloarthritis (SpA) family of inflammatory rheumatic diseases. 

An enthesis is an attachment site of ligaments, tendons, and joint capsules to bone and is a key inflammatory target in SpA. It is a complex structure that dissipates biomechanical stress to preserve homeostasis. Entheses are anatomically and functionally integrated with bursa, fibrocartilage, and synovium in a synovial entheseal complex; biomechanical stress in this area may trigger inflammation. Enthesitis is an early manifestation of PsA that has been associated with radiographic peripheral/axial joint damage and severe disease, as well as reduced quality of life.

Enthesitis can be difficult to diagnose in clinical practice. Symptoms include tenderness, soreness, and pain at entheses on palpation, often without overt clinical evidence of inflammation. In contrast, dactylitis, another hallmark manifestation of PsA, can be recognized by swelling of an entire digit that is different from adjacent digits. Fibromyalgia frequently coexists with enthesitis, and it can be difficult to distinguish the two given the anatomic overlap between the tender points of fibromyalgia and many entheseal sites. Long-lasting morning stiffness and a sustained response to a course of steroids is more suggestive of enthesitis, whereas a higher number of somatoform symptoms is more suggestive of fibromyalgia.

Enthesitis is included in the Classification Criteria for Psoriatic Arthritis (CASPAR) as a hallmark of PsA. While it can be diagnosed clinically, imaging studies may be required, particularly in patients in whom symptoms may be difficult to discern. Evidence of enthesitis by conventional radiography includes bone cortex irregularities, erosions, entheseal soft tissue calcifications, and new bone formation; however, entheseal bone changes detected with conventional radiography appear relatively late in the disease process. Ultrasound is highly sensitive for assessing inflammation and can detect various features of enthesitis, such as increased thickness of tendon insertion, hypoechogenicity, erosions, enthesophytes, and subclinical enthesitis in people with PsA. MRI has the advantage of identifying perientheseal inflammation with adjacent bone marrow edema. Fat-suppressed MRI with or without gadolinium enhancement is a highly sensitive method for visualizing active enthesitis and can identify perientheseal inflammation with adjacent bone marrow edema. 

Delayed treatment of PsA can result in irreversible joint damage and reduced quality of life; thus, patients with psoriasis should be closely monitored for early signs of its development, such as enthesitis. A thorough evaluation of the key clinical features of PsA (psoriasis, arthritis, enthesitis, dactylitis, and spondylitis), including evaluation of severity of each feature and impact on physical function and quality of life, is encouraged at each clinical encounter. Because patients may not understand the link between psoriasis and joint pain, specific probing questions can be helpful. Screening questionnaires to detect early signs and symptoms of PsA are available, such as the Psoriasis Epidemiology Screening Tool (PEST), Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire, and Toronto Psoriatic Arthritis Screening (ToPAS) questionnaire. These and many others may be used to help dermatologists detect early signs and symptoms of PsA. Although these questionnaires all have limitations in sensitivity and specificity for the diagnosis of PsA, their use can still improve early diagnosis.

The treatment of PsA focuses on achieving the least amount of disease activity and inflammation possible; optimizing functional status, quality of life, and well-being; and preventing structural damage. Treatment decisions are based on the specific domains affected. Nonsteroidal anti-inflammatory drugs and corticosteroid injections are first-line treatments for enthesitis. Early use of tumor necrosis factor inhibitors (TNF) (adalimumab, certolizumab pegol, etanercept, infliximab, and golimumab) is recommended. Alternative biologic disease-modifying agents are indicated when these TNF inhibitors provide an inadequate response. They include ustekinumab (dual interleukin [IL]-12 and IL-23 inhibitor), secukinumab (IL-17A inhibitor), and apremilast (phosphodiesterase-4 inhibitor) and may be considered for patients with predominantly entheseal manifestations of PsA or dactylitis. Biological disease-modifying agents approved for PsA that have shown efficacy for enthesitis include ixekizumab (which targets IL-17A), abatacept (a T-cell inhibitor), guselkumab (monoclonal antibody), and ustekinumab (monoclonal antibody). Tofacitinib and upadacitinib, both oral Janus kinase inhibitors, may also be considered. 

Herbert S. Diamond, MD, Professor of Medicine (retired), Temple University School of Medicine, University of Pittsburgh; Chairman, Department of Medicine Emeritus, Western Pennsylvania Hospital, Pittsburgh, PA.

Herbert S. Diamond, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's findings are consistent with a diagnosis of psoriatic enthesitis.

Enthesitis is a hallmark manifestation of psoriatic arthritis (PsA). Approximately 30% of patients with psoriasis are estimated to be affected by PsA, which belongs to the spondyloarthritis (SpA) family of inflammatory rheumatic diseases. 

An enthesis is an attachment site of ligaments, tendons, and joint capsules to bone and is a key inflammatory target in SpA. It is a complex structure that dissipates biomechanical stress to preserve homeostasis. Entheses are anatomically and functionally integrated with bursa, fibrocartilage, and synovium in a synovial entheseal complex; biomechanical stress in this area may trigger inflammation. Enthesitis is an early manifestation of PsA that has been associated with radiographic peripheral/axial joint damage and severe disease, as well as reduced quality of life.

Enthesitis can be difficult to diagnose in clinical practice. Symptoms include tenderness, soreness, and pain at entheses on palpation, often without overt clinical evidence of inflammation. In contrast, dactylitis, another hallmark manifestation of PsA, can be recognized by swelling of an entire digit that is different from adjacent digits. Fibromyalgia frequently coexists with enthesitis, and it can be difficult to distinguish the two given the anatomic overlap between the tender points of fibromyalgia and many entheseal sites. Long-lasting morning stiffness and a sustained response to a course of steroids is more suggestive of enthesitis, whereas a higher number of somatoform symptoms is more suggestive of fibromyalgia.

Enthesitis is included in the Classification Criteria for Psoriatic Arthritis (CASPAR) as a hallmark of PsA. While it can be diagnosed clinically, imaging studies may be required, particularly in patients in whom symptoms may be difficult to discern. Evidence of enthesitis by conventional radiography includes bone cortex irregularities, erosions, entheseal soft tissue calcifications, and new bone formation; however, entheseal bone changes detected with conventional radiography appear relatively late in the disease process. Ultrasound is highly sensitive for assessing inflammation and can detect various features of enthesitis, such as increased thickness of tendon insertion, hypoechogenicity, erosions, enthesophytes, and subclinical enthesitis in people with PsA. MRI has the advantage of identifying perientheseal inflammation with adjacent bone marrow edema. Fat-suppressed MRI with or without gadolinium enhancement is a highly sensitive method for visualizing active enthesitis and can identify perientheseal inflammation with adjacent bone marrow edema. 

Delayed treatment of PsA can result in irreversible joint damage and reduced quality of life; thus, patients with psoriasis should be closely monitored for early signs of its development, such as enthesitis. A thorough evaluation of the key clinical features of PsA (psoriasis, arthritis, enthesitis, dactylitis, and spondylitis), including evaluation of severity of each feature and impact on physical function and quality of life, is encouraged at each clinical encounter. Because patients may not understand the link between psoriasis and joint pain, specific probing questions can be helpful. Screening questionnaires to detect early signs and symptoms of PsA are available, such as the Psoriasis Epidemiology Screening Tool (PEST), Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire, and Toronto Psoriatic Arthritis Screening (ToPAS) questionnaire. These and many others may be used to help dermatologists detect early signs and symptoms of PsA. Although these questionnaires all have limitations in sensitivity and specificity for the diagnosis of PsA, their use can still improve early diagnosis.

The treatment of PsA focuses on achieving the least amount of disease activity and inflammation possible; optimizing functional status, quality of life, and well-being; and preventing structural damage. Treatment decisions are based on the specific domains affected. Nonsteroidal anti-inflammatory drugs and corticosteroid injections are first-line treatments for enthesitis. Early use of tumor necrosis factor inhibitors (TNF) (adalimumab, certolizumab pegol, etanercept, infliximab, and golimumab) is recommended. Alternative biologic disease-modifying agents are indicated when these TNF inhibitors provide an inadequate response. They include ustekinumab (dual interleukin [IL]-12 and IL-23 inhibitor), secukinumab (IL-17A inhibitor), and apremilast (phosphodiesterase-4 inhibitor) and may be considered for patients with predominantly entheseal manifestations of PsA or dactylitis. Biological disease-modifying agents approved for PsA that have shown efficacy for enthesitis include ixekizumab (which targets IL-17A), abatacept (a T-cell inhibitor), guselkumab (monoclonal antibody), and ustekinumab (monoclonal antibody). Tofacitinib and upadacitinib, both oral Janus kinase inhibitors, may also be considered. 

Herbert S. Diamond, MD, Professor of Medicine (retired), Temple University School of Medicine, University of Pittsburgh; Chairman, Department of Medicine Emeritus, Western Pennsylvania Hospital, Pittsburgh, PA.

Herbert S. Diamond, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Based on this patient's history and presentation, the likely diagnosis is primary progressive multiple sclerosis (PPMS). PPMS represents around 10% of MS cases and tends to develop about a decade later than relapsing MS. Unlike other forms of MS, this phenotype progresses steadily instead of in an episodic fashion like relapsing forms of MS. Most patients with PPMS present with gait difficulty because lesions often develop on the spinal cord. While relapsing-remitting MS (RRMS) is much more common among women than men, men with MS are more likely to have the progressive form. 

Although this patient's MRI ultimately points to multiple sclerosis, his functional deficits may initially suggest other conditions in the differential diagnosis. Brainstem gliomas typically manifest in unsteady gait, weakness, double vision, difficulty swallowing, dysarthria, headache, drowsiness, nausea, and vomiting. Transverse myelitis often presents with rapid-onset weakness, sensory deficits, and bowel/bladder dysfunction. Musculoskeletal and neurologic symptoms are common in Lyme disease. B12 deficiency can present with worsening weakness and a sensory ataxia that can present as balance difficulties, but it would not cause focal lesions on the MRI, nor would it present with bladder symptoms. In addition, the patient's steady decline in function rules out RRMS.

PPMS is diagnosed with confirmation of gradual change in functional ability (often ambulation) over time without remission or relapse. These criteria include 1 full year of worsening neurologic function without asymptomatic periods as well as two of these signs of disease: brain lesion, two or more spinal cord lesions, and oligoclonal bands or elevated Immunoglobulin G index. These timing-specific criteria can delay diagnosis, as seen here. 

Ocrelizumab is the only FDA-approved disease-modifying therapy (DMT) proven to alter disease progression in ambulatory patients with PPMS. American Academy of Neurology guidelines recommend ocrelizumab for patients with PPMS who are likely to benefit from this therapy. While it is thought that DMTs are more effective at targeting inflammation in RRMS than nerve degeneration in PPMS, these agents may show benefit for patients with active PPMS (relapse and/or evidence of new MRI activity) rather than inactive disease. A recent PPMS study concluded that among patients with relapse or disease activity, DMTs were associated with a significant reduction of long-term disability risk. Together with immunomodulatory therapy, rehabilitation can help manage symptoms.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ.

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Based on this patient's history and presentation, the likely diagnosis is primary progressive multiple sclerosis (PPMS). PPMS represents around 10% of MS cases and tends to develop about a decade later than relapsing MS. Unlike other forms of MS, this phenotype progresses steadily instead of in an episodic fashion like relapsing forms of MS. Most patients with PPMS present with gait difficulty because lesions often develop on the spinal cord. While relapsing-remitting MS (RRMS) is much more common among women than men, men with MS are more likely to have the progressive form. 

Although this patient's MRI ultimately points to multiple sclerosis, his functional deficits may initially suggest other conditions in the differential diagnosis. Brainstem gliomas typically manifest in unsteady gait, weakness, double vision, difficulty swallowing, dysarthria, headache, drowsiness, nausea, and vomiting. Transverse myelitis often presents with rapid-onset weakness, sensory deficits, and bowel/bladder dysfunction. Musculoskeletal and neurologic symptoms are common in Lyme disease. B12 deficiency can present with worsening weakness and a sensory ataxia that can present as balance difficulties, but it would not cause focal lesions on the MRI, nor would it present with bladder symptoms. In addition, the patient's steady decline in function rules out RRMS.

PPMS is diagnosed with confirmation of gradual change in functional ability (often ambulation) over time without remission or relapse. These criteria include 1 full year of worsening neurologic function without asymptomatic periods as well as two of these signs of disease: brain lesion, two or more spinal cord lesions, and oligoclonal bands or elevated Immunoglobulin G index. These timing-specific criteria can delay diagnosis, as seen here. 

Ocrelizumab is the only FDA-approved disease-modifying therapy (DMT) proven to alter disease progression in ambulatory patients with PPMS. American Academy of Neurology guidelines recommend ocrelizumab for patients with PPMS who are likely to benefit from this therapy. While it is thought that DMTs are more effective at targeting inflammation in RRMS than nerve degeneration in PPMS, these agents may show benefit for patients with active PPMS (relapse and/or evidence of new MRI activity) rather than inactive disease. A recent PPMS study concluded that among patients with relapse or disease activity, DMTs were associated with a significant reduction of long-term disability risk. Together with immunomodulatory therapy, rehabilitation can help manage symptoms.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ.

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Based on this patient's history and presentation, the likely diagnosis is primary progressive multiple sclerosis (PPMS). PPMS represents around 10% of MS cases and tends to develop about a decade later than relapsing MS. Unlike other forms of MS, this phenotype progresses steadily instead of in an episodic fashion like relapsing forms of MS. Most patients with PPMS present with gait difficulty because lesions often develop on the spinal cord. While relapsing-remitting MS (RRMS) is much more common among women than men, men with MS are more likely to have the progressive form. 

Although this patient's MRI ultimately points to multiple sclerosis, his functional deficits may initially suggest other conditions in the differential diagnosis. Brainstem gliomas typically manifest in unsteady gait, weakness, double vision, difficulty swallowing, dysarthria, headache, drowsiness, nausea, and vomiting. Transverse myelitis often presents with rapid-onset weakness, sensory deficits, and bowel/bladder dysfunction. Musculoskeletal and neurologic symptoms are common in Lyme disease. B12 deficiency can present with worsening weakness and a sensory ataxia that can present as balance difficulties, but it would not cause focal lesions on the MRI, nor would it present with bladder symptoms. In addition, the patient's steady decline in function rules out RRMS.

PPMS is diagnosed with confirmation of gradual change in functional ability (often ambulation) over time without remission or relapse. These criteria include 1 full year of worsening neurologic function without asymptomatic periods as well as two of these signs of disease: brain lesion, two or more spinal cord lesions, and oligoclonal bands or elevated Immunoglobulin G index. These timing-specific criteria can delay diagnosis, as seen here. 

Ocrelizumab is the only FDA-approved disease-modifying therapy (DMT) proven to alter disease progression in ambulatory patients with PPMS. American Academy of Neurology guidelines recommend ocrelizumab for patients with PPMS who are likely to benefit from this therapy. While it is thought that DMTs are more effective at targeting inflammation in RRMS than nerve degeneration in PPMS, these agents may show benefit for patients with active PPMS (relapse and/or evidence of new MRI activity) rather than inactive disease. A recent PPMS study concluded that among patients with relapse or disease activity, DMTs were associated with a significant reduction of long-term disability risk. Together with immunomodulatory therapy, rehabilitation can help manage symptoms.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ.

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's physical examination and imaging findings are consistent with a diagnosis of acute severe asthma. Agitation, breathlessness during rest, and a respiratory rate > 30 breaths/min are some manifestations of an acute severe episode. During severe episodes, accessory muscles of respiration are usually used, and suprasternal retractions are often present. The heart rate is > 120 beats/min and the respiratory rate is > 30 breaths/min. Loud biphasic (expiratory and inspiratory) wheezing can be heard, and pulsus paradoxus is often present (20-40 mm Hg). Oxyhemoglobin saturation with room air is < 91%. As the severity increases, the patient increasingly assumes a hunched-over sitting position with the hands supporting the torso, termed the tripod position.

Asthma is a chronic, heterogenous inflammatory airway disorder characterized by variable expiratory flow; airway wall thickening; respiratory symptoms; and exacerbations, which sometimes require hospitalization. According to the World Health Organization, asthma affected an estimated 262 million people in 2019. The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to various exogenous and endogenous stimuli. Mechanisms implicated in the development of asthma include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells, such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness is associated with the clinical severity of asthma.

Acute severe asthma is a life-threatening emergency characterized by severe airflow limitation that is unresponsive to the typical appropriate bronchodilator therapy. As a result of pathophysiologic changes, airflow is severely restricted in severe asthma, leading to premature closure of the airway on expiration; impaired gas exchange; and dynamic hyperinflation, or air-trapping. In such cases, urgent action is essential to thwart serious outcomes, including mechanical ventilation and death. 

Asthma severity is defined by the level of treatment required to control a patient's symptoms and exacerbations. According to the 2022 Global Initiative for Asthma (GINA) guidelines, a severe asthma exacerbation describes a patient who talks in words (rather than sentences); leans forward; is agitated; uses accessory respiratory muscles; and has a respiratory rate > 30 breaths/min, heart rate > 120 beats/min, oxygen saturation on air < 90%, and peak expiratory flow ≤ 50% of their best or of predicted value. Given the heterogeneity of asthma, patients with acute severe asthma may present with a variety of signs and symptoms, including dyspnea, chest tightness, cough and wheezing, agitation, drowsiness or signs of confusion, and significant breathlessness at rest. 

Exposure to external agents, such as indoor and outdoor allergens, air pollutants, and respiratory tract infections (primarily viral), are the most common causes of asthma exacerbations, which vary in severity. Numerous other factors can trigger an asthma exacerbation, including exercise, weather changes, certain foods, additives, drugs, extreme emotional expressions, rhinitis, sinusitis, polyposis, gastroesophageal reflux, menstruation, and pregnancy. Importantly, a patient with known asthma of any level of severity can experience an asthma exacerbation, including patients with mild or well-controlled asthma.

Patients with a history of poorly controlled asthma or a recent exacerbation are at risk for an acute asthma exacerbation. Other risk factors include poor perception of airflow limitation, regular or overuse of short-acting beta agonists, incorrect inhaler technique, and suboptimal adherence to therapy. Comorbidities associated with risk for an acute asthma exacerbation include obesity, chronic rhinosinusitis, inducible laryngeal obstruction (vocal cord dysfunction), gastroesophageal reflux disease, chronic obstructive pulmonary disease, obstructive sleep apnea, bronchiectasis, cardiac disease, and kyphosis due to osteoporosis (followed by corticosteroid overuse). The lack of a written asthma action plan and socioeconomic factors are also associated with increased risk for a severe exacerbation.

In the emergency department setting, pharmacologic therapy of acute severe asthma should consist of a short-acting beta agonist, ipratropium bromide, systemic corticosteroids (oral or intravenous), and controlled oxygen therapy. Clinicians may also consider intravenous magnesium sulfate and high-dose inhaled corticosteroids. Once stable, patients should be treated with optimal asthma-controlling therapy, as outlined in GINA guidelines. Optimizing patients' inhaler technique and adherence to therapy are imperative, and comorbidities should be appropriately managed. Nonpharmacologic interventions, such as smoking cessation, pulmonary rehabilitation, exercise, weight loss, and influenza/COVID-19 vaccination, are also recommended as indicated.

Zab Mosenifar, MD, Medical Director, Women's Lung Institute; Executive Vice Chairman, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, California.

Zab Mosenifar, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's physical examination and imaging findings are consistent with a diagnosis of acute severe asthma. Agitation, breathlessness during rest, and a respiratory rate > 30 breaths/min are some manifestations of an acute severe episode. During severe episodes, accessory muscles of respiration are usually used, and suprasternal retractions are often present. The heart rate is > 120 beats/min and the respiratory rate is > 30 breaths/min. Loud biphasic (expiratory and inspiratory) wheezing can be heard, and pulsus paradoxus is often present (20-40 mm Hg). Oxyhemoglobin saturation with room air is < 91%. As the severity increases, the patient increasingly assumes a hunched-over sitting position with the hands supporting the torso, termed the tripod position.

Asthma is a chronic, heterogenous inflammatory airway disorder characterized by variable expiratory flow; airway wall thickening; respiratory symptoms; and exacerbations, which sometimes require hospitalization. According to the World Health Organization, asthma affected an estimated 262 million people in 2019. The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to various exogenous and endogenous stimuli. Mechanisms implicated in the development of asthma include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells, such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness is associated with the clinical severity of asthma.

Acute severe asthma is a life-threatening emergency characterized by severe airflow limitation that is unresponsive to the typical appropriate bronchodilator therapy. As a result of pathophysiologic changes, airflow is severely restricted in severe asthma, leading to premature closure of the airway on expiration; impaired gas exchange; and dynamic hyperinflation, or air-trapping. In such cases, urgent action is essential to thwart serious outcomes, including mechanical ventilation and death. 

Asthma severity is defined by the level of treatment required to control a patient's symptoms and exacerbations. According to the 2022 Global Initiative for Asthma (GINA) guidelines, a severe asthma exacerbation describes a patient who talks in words (rather than sentences); leans forward; is agitated; uses accessory respiratory muscles; and has a respiratory rate > 30 breaths/min, heart rate > 120 beats/min, oxygen saturation on air < 90%, and peak expiratory flow ≤ 50% of their best or of predicted value. Given the heterogeneity of asthma, patients with acute severe asthma may present with a variety of signs and symptoms, including dyspnea, chest tightness, cough and wheezing, agitation, drowsiness or signs of confusion, and significant breathlessness at rest. 

Exposure to external agents, such as indoor and outdoor allergens, air pollutants, and respiratory tract infections (primarily viral), are the most common causes of asthma exacerbations, which vary in severity. Numerous other factors can trigger an asthma exacerbation, including exercise, weather changes, certain foods, additives, drugs, extreme emotional expressions, rhinitis, sinusitis, polyposis, gastroesophageal reflux, menstruation, and pregnancy. Importantly, a patient with known asthma of any level of severity can experience an asthma exacerbation, including patients with mild or well-controlled asthma.

Patients with a history of poorly controlled asthma or a recent exacerbation are at risk for an acute asthma exacerbation. Other risk factors include poor perception of airflow limitation, regular or overuse of short-acting beta agonists, incorrect inhaler technique, and suboptimal adherence to therapy. Comorbidities associated with risk for an acute asthma exacerbation include obesity, chronic rhinosinusitis, inducible laryngeal obstruction (vocal cord dysfunction), gastroesophageal reflux disease, chronic obstructive pulmonary disease, obstructive sleep apnea, bronchiectasis, cardiac disease, and kyphosis due to osteoporosis (followed by corticosteroid overuse). The lack of a written asthma action plan and socioeconomic factors are also associated with increased risk for a severe exacerbation.

In the emergency department setting, pharmacologic therapy of acute severe asthma should consist of a short-acting beta agonist, ipratropium bromide, systemic corticosteroids (oral or intravenous), and controlled oxygen therapy. Clinicians may also consider intravenous magnesium sulfate and high-dose inhaled corticosteroids. Once stable, patients should be treated with optimal asthma-controlling therapy, as outlined in GINA guidelines. Optimizing patients' inhaler technique and adherence to therapy are imperative, and comorbidities should be appropriately managed. Nonpharmacologic interventions, such as smoking cessation, pulmonary rehabilitation, exercise, weight loss, and influenza/COVID-19 vaccination, are also recommended as indicated.

Zab Mosenifar, MD, Medical Director, Women's Lung Institute; Executive Vice Chairman, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, California.

Zab Mosenifar, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's physical examination and imaging findings are consistent with a diagnosis of acute severe asthma. Agitation, breathlessness during rest, and a respiratory rate > 30 breaths/min are some manifestations of an acute severe episode. During severe episodes, accessory muscles of respiration are usually used, and suprasternal retractions are often present. The heart rate is > 120 beats/min and the respiratory rate is > 30 breaths/min. Loud biphasic (expiratory and inspiratory) wheezing can be heard, and pulsus paradoxus is often present (20-40 mm Hg). Oxyhemoglobin saturation with room air is < 91%. As the severity increases, the patient increasingly assumes a hunched-over sitting position with the hands supporting the torso, termed the tripod position.

Asthma is a chronic, heterogenous inflammatory airway disorder characterized by variable expiratory flow; airway wall thickening; respiratory symptoms; and exacerbations, which sometimes require hospitalization. According to the World Health Organization, asthma affected an estimated 262 million people in 2019. The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to various exogenous and endogenous stimuli. Mechanisms implicated in the development of asthma include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells, such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness is associated with the clinical severity of asthma.

Acute severe asthma is a life-threatening emergency characterized by severe airflow limitation that is unresponsive to the typical appropriate bronchodilator therapy. As a result of pathophysiologic changes, airflow is severely restricted in severe asthma, leading to premature closure of the airway on expiration; impaired gas exchange; and dynamic hyperinflation, or air-trapping. In such cases, urgent action is essential to thwart serious outcomes, including mechanical ventilation and death. 

Asthma severity is defined by the level of treatment required to control a patient's symptoms and exacerbations. According to the 2022 Global Initiative for Asthma (GINA) guidelines, a severe asthma exacerbation describes a patient who talks in words (rather than sentences); leans forward; is agitated; uses accessory respiratory muscles; and has a respiratory rate > 30 breaths/min, heart rate > 120 beats/min, oxygen saturation on air < 90%, and peak expiratory flow ≤ 50% of their best or of predicted value. Given the heterogeneity of asthma, patients with acute severe asthma may present with a variety of signs and symptoms, including dyspnea, chest tightness, cough and wheezing, agitation, drowsiness or signs of confusion, and significant breathlessness at rest. 

Exposure to external agents, such as indoor and outdoor allergens, air pollutants, and respiratory tract infections (primarily viral), are the most common causes of asthma exacerbations, which vary in severity. Numerous other factors can trigger an asthma exacerbation, including exercise, weather changes, certain foods, additives, drugs, extreme emotional expressions, rhinitis, sinusitis, polyposis, gastroesophageal reflux, menstruation, and pregnancy. Importantly, a patient with known asthma of any level of severity can experience an asthma exacerbation, including patients with mild or well-controlled asthma.

Patients with a history of poorly controlled asthma or a recent exacerbation are at risk for an acute asthma exacerbation. Other risk factors include poor perception of airflow limitation, regular or overuse of short-acting beta agonists, incorrect inhaler technique, and suboptimal adherence to therapy. Comorbidities associated with risk for an acute asthma exacerbation include obesity, chronic rhinosinusitis, inducible laryngeal obstruction (vocal cord dysfunction), gastroesophageal reflux disease, chronic obstructive pulmonary disease, obstructive sleep apnea, bronchiectasis, cardiac disease, and kyphosis due to osteoporosis (followed by corticosteroid overuse). The lack of a written asthma action plan and socioeconomic factors are also associated with increased risk for a severe exacerbation.

In the emergency department setting, pharmacologic therapy of acute severe asthma should consist of a short-acting beta agonist, ipratropium bromide, systemic corticosteroids (oral or intravenous), and controlled oxygen therapy. Clinicians may also consider intravenous magnesium sulfate and high-dose inhaled corticosteroids. Once stable, patients should be treated with optimal asthma-controlling therapy, as outlined in GINA guidelines. Optimizing patients' inhaler technique and adherence to therapy are imperative, and comorbidities should be appropriately managed. Nonpharmacologic interventions, such as smoking cessation, pulmonary rehabilitation, exercise, weight loss, and influenza/COVID-19 vaccination, are also recommended as indicated.

Zab Mosenifar, MD, Medical Director, Women's Lung Institute; Executive Vice Chairman, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, California.

Zab Mosenifar, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's physical findings are consistent with a diagnosis of claw toe, which can be caused by diabetes-related peripheral neuropathy.

According to the International Diabetes Federation, diabetes currently affects approximately 537 million adults worldwide. The number of individuals living with diabetes is expected to exceed 640 million by 2030 and 780 million by 2045. In the United States, more than 37 million people are living with diabetes.

Foot complications related to diabetes represent a significant economic and social burden and can profoundly affect a patient's quality of life and medical outcomes. Common diabetes-related foot complications include foot deformity and peripheral neuropathy, both of which increase the risk for ulceration and amputation. The most common deformity is at the metatarsophalangeal joint (MTPJ). As many as 85% of patients with a history of ulcers and amputation have an MTPJ deformity such as claw toe or hammertoe.

Although they are often grouped together, claw toe and hammertoe have distinct features. Extended MTPJ, flexed proximal interphalangeal joint (PIPJ), and flexed distal interphalangeal joint (DIPJ) are characteristic of claw toe. While hammertoe also has extended MTPJ and flexed PIPJ, the DIPJ is extended rather than flexed. In both cases, the area of high pressure at risk for skin breakdown and ulceration is at the metatarsal head as a result of MTPJ hyperextension deformity. 

Prompt detection and care of diabetes-related foot complications can minimize progression and negative consequences on patients' health and quality of life. According to the American Diabetes Association, all patients with diabetes should undergo a comprehensive foot evaluation at least annually to identify risk factors for ulceration and amputation, which include foot deformities, poor glycemic control, peripheral neuropathy, cigarette smoking, preulcerative callus or corn, peripheral artery disease, chronic kidney disease, visual impairment, and a history of ulceration or amputation. When patients present with a history of ulceration or amputation, a foot inspection should be conducted at each visit. 

A comprehensive foot evaluation should include inspection of the skin, evaluation of any foot deformities, a neurologic assessment (10-g monofilament testing with at least one other assessment: pinprick, temperature, vibration), and a vascular assessment, including pulses in the legs and feet.

Patients should be educated on risk factors and appropriate management of foot-related complications, including the importance of effective glycemic control and daily monitoring of feet. Treatment may be medical, surgical, or both, as indicated by the individual patient's presentation. Conservative treatment approaches include footwear that is extra wide or deep, avoiding high-heeled and narrow-toed shoes, use of a metatarsal bar or pad, cushioning sleeves or stocking caps with silicon linings, and a longitudinal pad beneath the toes.

Complete recommendations on achieving glycemic control in T2D can be found in the 2022 American Diabetes Association Standards of Medical Care. Guidelines on foot care are also available.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's physical findings are consistent with a diagnosis of claw toe, which can be caused by diabetes-related peripheral neuropathy.

According to the International Diabetes Federation, diabetes currently affects approximately 537 million adults worldwide. The number of individuals living with diabetes is expected to exceed 640 million by 2030 and 780 million by 2045. In the United States, more than 37 million people are living with diabetes.

Foot complications related to diabetes represent a significant economic and social burden and can profoundly affect a patient's quality of life and medical outcomes. Common diabetes-related foot complications include foot deformity and peripheral neuropathy, both of which increase the risk for ulceration and amputation. The most common deformity is at the metatarsophalangeal joint (MTPJ). As many as 85% of patients with a history of ulcers and amputation have an MTPJ deformity such as claw toe or hammertoe.

Although they are often grouped together, claw toe and hammertoe have distinct features. Extended MTPJ, flexed proximal interphalangeal joint (PIPJ), and flexed distal interphalangeal joint (DIPJ) are characteristic of claw toe. While hammertoe also has extended MTPJ and flexed PIPJ, the DIPJ is extended rather than flexed. In both cases, the area of high pressure at risk for skin breakdown and ulceration is at the metatarsal head as a result of MTPJ hyperextension deformity. 

Prompt detection and care of diabetes-related foot complications can minimize progression and negative consequences on patients' health and quality of life. According to the American Diabetes Association, all patients with diabetes should undergo a comprehensive foot evaluation at least annually to identify risk factors for ulceration and amputation, which include foot deformities, poor glycemic control, peripheral neuropathy, cigarette smoking, preulcerative callus or corn, peripheral artery disease, chronic kidney disease, visual impairment, and a history of ulceration or amputation. When patients present with a history of ulceration or amputation, a foot inspection should be conducted at each visit. 

A comprehensive foot evaluation should include inspection of the skin, evaluation of any foot deformities, a neurologic assessment (10-g monofilament testing with at least one other assessment: pinprick, temperature, vibration), and a vascular assessment, including pulses in the legs and feet.

Patients should be educated on risk factors and appropriate management of foot-related complications, including the importance of effective glycemic control and daily monitoring of feet. Treatment may be medical, surgical, or both, as indicated by the individual patient's presentation. Conservative treatment approaches include footwear that is extra wide or deep, avoiding high-heeled and narrow-toed shoes, use of a metatarsal bar or pad, cushioning sleeves or stocking caps with silicon linings, and a longitudinal pad beneath the toes.

Complete recommendations on achieving glycemic control in T2D can be found in the 2022 American Diabetes Association Standards of Medical Care. Guidelines on foot care are also available.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's physical findings are consistent with a diagnosis of claw toe, which can be caused by diabetes-related peripheral neuropathy.

According to the International Diabetes Federation, diabetes currently affects approximately 537 million adults worldwide. The number of individuals living with diabetes is expected to exceed 640 million by 2030 and 780 million by 2045. In the United States, more than 37 million people are living with diabetes.

Foot complications related to diabetes represent a significant economic and social burden and can profoundly affect a patient's quality of life and medical outcomes. Common diabetes-related foot complications include foot deformity and peripheral neuropathy, both of which increase the risk for ulceration and amputation. The most common deformity is at the metatarsophalangeal joint (MTPJ). As many as 85% of patients with a history of ulcers and amputation have an MTPJ deformity such as claw toe or hammertoe.

Although they are often grouped together, claw toe and hammertoe have distinct features. Extended MTPJ, flexed proximal interphalangeal joint (PIPJ), and flexed distal interphalangeal joint (DIPJ) are characteristic of claw toe. While hammertoe also has extended MTPJ and flexed PIPJ, the DIPJ is extended rather than flexed. In both cases, the area of high pressure at risk for skin breakdown and ulceration is at the metatarsal head as a result of MTPJ hyperextension deformity. 

Prompt detection and care of diabetes-related foot complications can minimize progression and negative consequences on patients' health and quality of life. According to the American Diabetes Association, all patients with diabetes should undergo a comprehensive foot evaluation at least annually to identify risk factors for ulceration and amputation, which include foot deformities, poor glycemic control, peripheral neuropathy, cigarette smoking, preulcerative callus or corn, peripheral artery disease, chronic kidney disease, visual impairment, and a history of ulceration or amputation. When patients present with a history of ulceration or amputation, a foot inspection should be conducted at each visit. 

A comprehensive foot evaluation should include inspection of the skin, evaluation of any foot deformities, a neurologic assessment (10-g monofilament testing with at least one other assessment: pinprick, temperature, vibration), and a vascular assessment, including pulses in the legs and feet.

Patients should be educated on risk factors and appropriate management of foot-related complications, including the importance of effective glycemic control and daily monitoring of feet. Treatment may be medical, surgical, or both, as indicated by the individual patient's presentation. Conservative treatment approaches include footwear that is extra wide or deep, avoiding high-heeled and narrow-toed shoes, use of a metatarsal bar or pad, cushioning sleeves or stocking caps with silicon linings, and a longitudinal pad beneath the toes.

Complete recommendations on achieving glycemic control in T2D can be found in the 2022 American Diabetes Association Standards of Medical Care. Guidelines on foot care are also available.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

On the basis of the patient’s family history, personal history, and presentation, the likely diagnosis is Crohn disease. Although the disease may be diagnosed at any age, onset shows a bimodal distribution, with the first, more predominant wave occurring in adolescence and early adulthood. Peak global onset is between the ages of 15 and 30. Compared with adult-onset disease, pediatric Crohn disease is associated with a more serious disease course. Patients of Ashkenazi Jewish descent are at higher risk of developing this autoimmune disease than any other ethnic group. 

Colonoscopy is the first-line approach for diagnosing and monitoring inflammatory bowel disease. Typical findings in patients with Crohn disease include histologic changes, such as focal crypt irregularity, transmural lymphoid aggregates, fissures and fistulas, and perianal disorders. In the differential diagnosis, ulcerative colitis (UC) must be carefully ruled out. UC involves only the large bowel, rarely causes fistulas, and is frequently seen with bleeding. Crohn disease is characteristically noncontiguous, with linear ulcerations of a cobblestone appearance. In addition, noncaseating granulomas are specific for Crohn disease. Micronutrient and vitamin levels are usually low, as seen in the present case. During workup, fecal calprotectin can help differentiate inflammatory bowel disease from irritable bowel syndrome. 

The patient in this case may be a candidate for 5-aminosalicylic acid, together with a nutritional plan, used in mild or moderate cases of pediatric Crohn disease. Clinical improvement plus a decrease of fecal calprotectin would be an indication of positive treatment response. Being newly diagnosed, if the patient does not achieve remission after the induction period, he may be at risk for a more complicated disease course. Treatment for Crohn disease in the pediatric setting, as in the adult setting, should be implemented through a step-up approach. Other treatment options for pediatric disease include antibiotics; immunomodulators; and, in moderate-to severe cases, corticosteroids and biologics.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

On the basis of the patient’s family history, personal history, and presentation, the likely diagnosis is Crohn disease. Although the disease may be diagnosed at any age, onset shows a bimodal distribution, with the first, more predominant wave occurring in adolescence and early adulthood. Peak global onset is between the ages of 15 and 30. Compared with adult-onset disease, pediatric Crohn disease is associated with a more serious disease course. Patients of Ashkenazi Jewish descent are at higher risk of developing this autoimmune disease than any other ethnic group. 

Colonoscopy is the first-line approach for diagnosing and monitoring inflammatory bowel disease. Typical findings in patients with Crohn disease include histologic changes, such as focal crypt irregularity, transmural lymphoid aggregates, fissures and fistulas, and perianal disorders. In the differential diagnosis, ulcerative colitis (UC) must be carefully ruled out. UC involves only the large bowel, rarely causes fistulas, and is frequently seen with bleeding. Crohn disease is characteristically noncontiguous, with linear ulcerations of a cobblestone appearance. In addition, noncaseating granulomas are specific for Crohn disease. Micronutrient and vitamin levels are usually low, as seen in the present case. During workup, fecal calprotectin can help differentiate inflammatory bowel disease from irritable bowel syndrome. 

The patient in this case may be a candidate for 5-aminosalicylic acid, together with a nutritional plan, used in mild or moderate cases of pediatric Crohn disease. Clinical improvement plus a decrease of fecal calprotectin would be an indication of positive treatment response. Being newly diagnosed, if the patient does not achieve remission after the induction period, he may be at risk for a more complicated disease course. Treatment for Crohn disease in the pediatric setting, as in the adult setting, should be implemented through a step-up approach. Other treatment options for pediatric disease include antibiotics; immunomodulators; and, in moderate-to severe cases, corticosteroids and biologics.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

On the basis of the patient’s family history, personal history, and presentation, the likely diagnosis is Crohn disease. Although the disease may be diagnosed at any age, onset shows a bimodal distribution, with the first, more predominant wave occurring in adolescence and early adulthood. Peak global onset is between the ages of 15 and 30. Compared with adult-onset disease, pediatric Crohn disease is associated with a more serious disease course. Patients of Ashkenazi Jewish descent are at higher risk of developing this autoimmune disease than any other ethnic group. 

Colonoscopy is the first-line approach for diagnosing and monitoring inflammatory bowel disease. Typical findings in patients with Crohn disease include histologic changes, such as focal crypt irregularity, transmural lymphoid aggregates, fissures and fistulas, and perianal disorders. In the differential diagnosis, ulcerative colitis (UC) must be carefully ruled out. UC involves only the large bowel, rarely causes fistulas, and is frequently seen with bleeding. Crohn disease is characteristically noncontiguous, with linear ulcerations of a cobblestone appearance. In addition, noncaseating granulomas are specific for Crohn disease. Micronutrient and vitamin levels are usually low, as seen in the present case. During workup, fecal calprotectin can help differentiate inflammatory bowel disease from irritable bowel syndrome. 

The patient in this case may be a candidate for 5-aminosalicylic acid, together with a nutritional plan, used in mild or moderate cases of pediatric Crohn disease. Clinical improvement plus a decrease of fecal calprotectin would be an indication of positive treatment response. Being newly diagnosed, if the patient does not achieve remission after the induction period, he may be at risk for a more complicated disease course. Treatment for Crohn disease in the pediatric setting, as in the adult setting, should be implemented through a step-up approach. Other treatment options for pediatric disease include antibiotics; immunomodulators; and, in moderate-to severe cases, corticosteroids and biologics.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

On the basis of the patient's presentation and described history, the likely diagnosis is migraine. By adolescence, migraine is much more common among female patients and can be connected to the menstrual cycle. The early symptoms before onset of head pain reported by this patient characterize the prodromal phase, which can occur 1-2 days before the headache, followed by the aura phase. Approximately one third of patients with migraine experience episodes with aura, like the visual disturbance described in this case. 

Migraine can be diagnosed on a clinical basis, but certain neurologic symptoms with headache should be considered red flags and prompt further workup (ie, stiff neck or fever, or history of head injury or major trauma). Spontaneous internal carotid artery dissection, for example, should be investigated in the differential of younger patients who have severe headache before onset of neurologic symptoms. Patients who present with migraine are very frequently misdiagnosed as having sinus headaches or sinusitis. Relevant clinical findings of acute sinusitis are sinus tenderness or pressure; pain over the cheek which radiates to the frontal region or teeth; redness of nose, cheeks, or eyelids; pain to the vertex, temple, or occiput; postnasal discharge; a blocked nose; coughing or pharyngeal irritation; facial pain; and hyposmia. Tension-type headaches usually are associated with mild or moderate bilateral pain, causing a steady ache as opposed to the throbbing of migraines. Basilar migraine, common among female patients, is marked by vertebrobasilar insufficiency. 

The American Headache Society defines migraine by the occurrence of at least five episodes. These attacks must last 4-72 hours and have at least two of these four characteristics: unilateral location, pulsating quality, moderate or severe pain intensity, and aggravation by or causing avoidance of routine physical activity. During these episodes, the patient must experience either photophobia and phonophobia or nausea and/or vomiting. If these signs and symptoms cannot be explained by another diagnosis, the patient is very likely presenting with migraine.

Identifying an effective treatment for migraines is often associated with a trial-and-error period, with an average 4-year gap between diagnosis and initiation of preventive medications. Because the patient's migraines do not seem to respond to non-steroidal anti inflammatory drugs, she may be a candidate for other treatments of mild-to-moderate migraines: nonopioid analgesics, acetaminophen, or caffeinated analgesic combinations. If attacks are moderate or severe, or even mild to moderate but do not respond well to therapy, migraine-specific agents are recommended: triptans, dihydroergotamine (DHE), small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists (gepants), and selective serotonin (5-HT1F) receptor agonists (ditans).

Jasmin Harpe, MD, MPH, Headache Fellow, Department of Neurology, Harvard University, John R. Graham Headache Center, Mass General Brigham, Boston, MA

Jasmin Harpe, MD, MPH, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

On the basis of the patient's presentation and described history, the likely diagnosis is migraine. By adolescence, migraine is much more common among female patients and can be connected to the menstrual cycle. The early symptoms before onset of head pain reported by this patient characterize the prodromal phase, which can occur 1-2 days before the headache, followed by the aura phase. Approximately one third of patients with migraine experience episodes with aura, like the visual disturbance described in this case. 

Migraine can be diagnosed on a clinical basis, but certain neurologic symptoms with headache should be considered red flags and prompt further workup (ie, stiff neck or fever, or history of head injury or major trauma). Spontaneous internal carotid artery dissection, for example, should be investigated in the differential of younger patients who have severe headache before onset of neurologic symptoms. Patients who present with migraine are very frequently misdiagnosed as having sinus headaches or sinusitis. Relevant clinical findings of acute sinusitis are sinus tenderness or pressure; pain over the cheek which radiates to the frontal region or teeth; redness of nose, cheeks, or eyelids; pain to the vertex, temple, or occiput; postnasal discharge; a blocked nose; coughing or pharyngeal irritation; facial pain; and hyposmia. Tension-type headaches usually are associated with mild or moderate bilateral pain, causing a steady ache as opposed to the throbbing of migraines. Basilar migraine, common among female patients, is marked by vertebrobasilar insufficiency. 

The American Headache Society defines migraine by the occurrence of at least five episodes. These attacks must last 4-72 hours and have at least two of these four characteristics: unilateral location, pulsating quality, moderate or severe pain intensity, and aggravation by or causing avoidance of routine physical activity. During these episodes, the patient must experience either photophobia and phonophobia or nausea and/or vomiting. If these signs and symptoms cannot be explained by another diagnosis, the patient is very likely presenting with migraine.

Identifying an effective treatment for migraines is often associated with a trial-and-error period, with an average 4-year gap between diagnosis and initiation of preventive medications. Because the patient's migraines do not seem to respond to non-steroidal anti inflammatory drugs, she may be a candidate for other treatments of mild-to-moderate migraines: nonopioid analgesics, acetaminophen, or caffeinated analgesic combinations. If attacks are moderate or severe, or even mild to moderate but do not respond well to therapy, migraine-specific agents are recommended: triptans, dihydroergotamine (DHE), small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists (gepants), and selective serotonin (5-HT1F) receptor agonists (ditans).

Jasmin Harpe, MD, MPH, Headache Fellow, Department of Neurology, Harvard University, John R. Graham Headache Center, Mass General Brigham, Boston, MA

Jasmin Harpe, MD, MPH, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

On the basis of the patient's presentation and described history, the likely diagnosis is migraine. By adolescence, migraine is much more common among female patients and can be connected to the menstrual cycle. The early symptoms before onset of head pain reported by this patient characterize the prodromal phase, which can occur 1-2 days before the headache, followed by the aura phase. Approximately one third of patients with migraine experience episodes with aura, like the visual disturbance described in this case. 

Migraine can be diagnosed on a clinical basis, but certain neurologic symptoms with headache should be considered red flags and prompt further workup (ie, stiff neck or fever, or history of head injury or major trauma). Spontaneous internal carotid artery dissection, for example, should be investigated in the differential of younger patients who have severe headache before onset of neurologic symptoms. Patients who present with migraine are very frequently misdiagnosed as having sinus headaches or sinusitis. Relevant clinical findings of acute sinusitis are sinus tenderness or pressure; pain over the cheek which radiates to the frontal region or teeth; redness of nose, cheeks, or eyelids; pain to the vertex, temple, or occiput; postnasal discharge; a blocked nose; coughing or pharyngeal irritation; facial pain; and hyposmia. Tension-type headaches usually are associated with mild or moderate bilateral pain, causing a steady ache as opposed to the throbbing of migraines. Basilar migraine, common among female patients, is marked by vertebrobasilar insufficiency. 

The American Headache Society defines migraine by the occurrence of at least five episodes. These attacks must last 4-72 hours and have at least two of these four characteristics: unilateral location, pulsating quality, moderate or severe pain intensity, and aggravation by or causing avoidance of routine physical activity. During these episodes, the patient must experience either photophobia and phonophobia or nausea and/or vomiting. If these signs and symptoms cannot be explained by another diagnosis, the patient is very likely presenting with migraine.

Identifying an effective treatment for migraines is often associated with a trial-and-error period, with an average 4-year gap between diagnosis and initiation of preventive medications. Because the patient's migraines do not seem to respond to non-steroidal anti inflammatory drugs, she may be a candidate for other treatments of mild-to-moderate migraines: nonopioid analgesics, acetaminophen, or caffeinated analgesic combinations. If attacks are moderate or severe, or even mild to moderate but do not respond well to therapy, migraine-specific agents are recommended: triptans, dihydroergotamine (DHE), small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists (gepants), and selective serotonin (5-HT1F) receptor agonists (ditans).

Jasmin Harpe, MD, MPH, Headache Fellow, Department of Neurology, Harvard University, John R. Graham Headache Center, Mass General Brigham, Boston, MA

Jasmin Harpe, MD, MPH, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

On the basis of this presentation, and the findings from the chest x-ray (as shown), the likely diagnosis is non–small cell lung cancer (NSCLC), Pancoast tumor, also known as superior sulcus tumor. Pancoast tumors are rare, representing about 3%-5% of all lung cancers, and invade the structures in the apex of the chest, including the first thoracic ribs or periosteum, the lower nerve roots of the bronchial plexus, the sympathetic chain and stellate ganglion, or the subclavian vessels. The majority of Pancoast tumors are non–small cell carcinomas.

Because of their pulmonary location, Pancoast tumors are characterized by several distinct symptoms. As seen in this case, patients often present with shoulder pain that worsens over time, especially with invasion of the chest wall and brachial plexus. The pain may radiate to the neck; axilla; anterior chest wall; and medial aspect of the arm, forearm, and wrist. If Pancoast tumors infiltrate the ulnar nerve, patients may present with weakness and muscle atrophy of the intrinsic muscles of the hand. In addition, invasion of the sympathetic chain and of the inferior cervical ganglion can cause Horner syndrome (ptosis, miosis, enophthalmos, and anhidrosis). Lastly, upper-arm edema may develop, signaling invasion and potentially occlusion of the subclavian vein.

During workup, CT-guided core biopsy is the first-line diagnostic test for Pancoast tumors. CT of the chest can confirm the presence of an apical mass and its position in relation to other structures of the thoracic inlet. MRI can further assess suspected brachial plexus, subclavian vessels, spine, and neural foramina invasion, specifying the extent of the disease and of the amount of nerve-root involvement.

For resectable Pancoast tumors, the National Comprehensive Cancer Network recommends chemoradiation, followed by surgical resection and chemotherapy. Preoperative chemoradiation together with surgical resection has shown a 2-year survival between 50% and 70%. Depending on biomarker status (certain EGFR mutations or programmed death ligand 1 levels ≥ 1%), the addition of either atezolizumab or osimertinib is advised. However, the positioning of Pancoast tumors can pose a surgical challenge, and if the lesion remains unresectable after preoperative concurrent chemoradiation, then consolidation immunotherapy with durvalumab is recommended.

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

On the basis of this presentation, and the findings from the chest x-ray (as shown), the likely diagnosis is non–small cell lung cancer (NSCLC), Pancoast tumor, also known as superior sulcus tumor. Pancoast tumors are rare, representing about 3%-5% of all lung cancers, and invade the structures in the apex of the chest, including the first thoracic ribs or periosteum, the lower nerve roots of the bronchial plexus, the sympathetic chain and stellate ganglion, or the subclavian vessels. The majority of Pancoast tumors are non–small cell carcinomas.

Because of their pulmonary location, Pancoast tumors are characterized by several distinct symptoms. As seen in this case, patients often present with shoulder pain that worsens over time, especially with invasion of the chest wall and brachial plexus. The pain may radiate to the neck; axilla; anterior chest wall; and medial aspect of the arm, forearm, and wrist. If Pancoast tumors infiltrate the ulnar nerve, patients may present with weakness and muscle atrophy of the intrinsic muscles of the hand. In addition, invasion of the sympathetic chain and of the inferior cervical ganglion can cause Horner syndrome (ptosis, miosis, enophthalmos, and anhidrosis). Lastly, upper-arm edema may develop, signaling invasion and potentially occlusion of the subclavian vein.

During workup, CT-guided core biopsy is the first-line diagnostic test for Pancoast tumors. CT of the chest can confirm the presence of an apical mass and its position in relation to other structures of the thoracic inlet. MRI can further assess suspected brachial plexus, subclavian vessels, spine, and neural foramina invasion, specifying the extent of the disease and of the amount of nerve-root involvement.

For resectable Pancoast tumors, the National Comprehensive Cancer Network recommends chemoradiation, followed by surgical resection and chemotherapy. Preoperative chemoradiation together with surgical resection has shown a 2-year survival between 50% and 70%. Depending on biomarker status (certain EGFR mutations or programmed death ligand 1 levels ≥ 1%), the addition of either atezolizumab or osimertinib is advised. However, the positioning of Pancoast tumors can pose a surgical challenge, and if the lesion remains unresectable after preoperative concurrent chemoradiation, then consolidation immunotherapy with durvalumab is recommended.

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

On the basis of this presentation, and the findings from the chest x-ray (as shown), the likely diagnosis is non–small cell lung cancer (NSCLC), Pancoast tumor, also known as superior sulcus tumor. Pancoast tumors are rare, representing about 3%-5% of all lung cancers, and invade the structures in the apex of the chest, including the first thoracic ribs or periosteum, the lower nerve roots of the bronchial plexus, the sympathetic chain and stellate ganglion, or the subclavian vessels. The majority of Pancoast tumors are non–small cell carcinomas.

Because of their pulmonary location, Pancoast tumors are characterized by several distinct symptoms. As seen in this case, patients often present with shoulder pain that worsens over time, especially with invasion of the chest wall and brachial plexus. The pain may radiate to the neck; axilla; anterior chest wall; and medial aspect of the arm, forearm, and wrist. If Pancoast tumors infiltrate the ulnar nerve, patients may present with weakness and muscle atrophy of the intrinsic muscles of the hand. In addition, invasion of the sympathetic chain and of the inferior cervical ganglion can cause Horner syndrome (ptosis, miosis, enophthalmos, and anhidrosis). Lastly, upper-arm edema may develop, signaling invasion and potentially occlusion of the subclavian vein.

During workup, CT-guided core biopsy is the first-line diagnostic test for Pancoast tumors. CT of the chest can confirm the presence of an apical mass and its position in relation to other structures of the thoracic inlet. MRI can further assess suspected brachial plexus, subclavian vessels, spine, and neural foramina invasion, specifying the extent of the disease and of the amount of nerve-root involvement.

For resectable Pancoast tumors, the National Comprehensive Cancer Network recommends chemoradiation, followed by surgical resection and chemotherapy. Preoperative chemoradiation together with surgical resection has shown a 2-year survival between 50% and 70%. Depending on biomarker status (certain EGFR mutations or programmed death ligand 1 levels ≥ 1%), the addition of either atezolizumab or osimertinib is advised. However, the positioning of Pancoast tumors can pose a surgical challenge, and if the lesion remains unresectable after preoperative concurrent chemoradiation, then consolidation immunotherapy with durvalumab is recommended.

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The diagnosis for this case is psoriatic arthritis (PsA). The 2018 American College of Rheumatology/National Psoriasis Foundation guidelines offer current treatment recommendations for this condition. For patients with active PsA who are treatment-naive, treatment recommendations are:

• Tumor necrosis factor (TNF) inhibitors are preferred over oral small molecules (OSMs), interleukin (IL)–17 inhibitors, or IL-12/23 inhibitors
• OSMs are recommended over IL-17 inhibitors or IL-12/23 inhibitors
• Methotrexate is recommended over nonsteroidal anti-inflammatory drugs
• IL-17 inhibitors are recommended over IL-12/23 inhibitors

Treatment recommendations for patients with active PsA despite the use of OSMs are: 

• Switching to a TNF inhibitor over another OSM, IL-17 or IL-12/23 inhibitors, abatacept, or tofacitinib
• Switching to an IL-17 inhibitor over another OSM, IL-12/23 inhibitor, abatacept, or tofacitinib
• Switching to an IL-12/23 inhibitor over another OSM, abatacept, or tofacitinib.

International groups, such as the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the European League Against Rheumatism (EULAR), have published treatment recommendations as well. These address both PsA and, to a lesser extent, psoriasis. The GRAPPA recommendations consider six domains of involvement (peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis, and nail psoriasis) and use a grid approach to account for various levels of disease activity and severity. The EULAR recommendations use an algorithmic approach that focuses mainly on musculoskeletal manifestations, specifically peripheral arthritis; manifestations, such as dactylitis, enthesitis, and skin and nail involvement, are considered separately.

Psoriasis precedes the onset of PsA in 60%-80% of patients (sometimes by up to 20 years but usually by less than 10 years); but in as many as 15%-20% of patients, arthritis appears before psoriasis. On occasion, arthritis and psoriasis appear simultaneously.

Patients with PsA are typically seronegative for rheumatoid factor and antinuclear antibody; antinuclear antibody titers in persons with PsA do not differ from those of age- and sex-matched controls. C-reactive protein may be elevated but is often normal. Lack of C-reactive protein elevation, however, does not mean that systemic inflammation is absent but rather indicates that a different type of systemic inflammation may be at play for those patients.

Herbert S. Diamond, MD, Professor of Medicine (retired), Temple University School of Medicine, University of Pittsburgh; Chairman, Department of Medicine Emeritus, Western Pennsylvania Hospital, Pittsburgh, PA.

Herbert S. Diamond, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The diagnosis for this case is psoriatic arthritis (PsA). The 2018 American College of Rheumatology/National Psoriasis Foundation guidelines offer current treatment recommendations for this condition. For patients with active PsA who are treatment-naive, treatment recommendations are:

• Tumor necrosis factor (TNF) inhibitors are preferred over oral small molecules (OSMs), interleukin (IL)–17 inhibitors, or IL-12/23 inhibitors
• OSMs are recommended over IL-17 inhibitors or IL-12/23 inhibitors
• Methotrexate is recommended over nonsteroidal anti-inflammatory drugs
• IL-17 inhibitors are recommended over IL-12/23 inhibitors

Treatment recommendations for patients with active PsA despite the use of OSMs are: 

• Switching to a TNF inhibitor over another OSM, IL-17 or IL-12/23 inhibitors, abatacept, or tofacitinib
• Switching to an IL-17 inhibitor over another OSM, IL-12/23 inhibitor, abatacept, or tofacitinib
• Switching to an IL-12/23 inhibitor over another OSM, abatacept, or tofacitinib.

International groups, such as the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the European League Against Rheumatism (EULAR), have published treatment recommendations as well. These address both PsA and, to a lesser extent, psoriasis. The GRAPPA recommendations consider six domains of involvement (peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis, and nail psoriasis) and use a grid approach to account for various levels of disease activity and severity. The EULAR recommendations use an algorithmic approach that focuses mainly on musculoskeletal manifestations, specifically peripheral arthritis; manifestations, such as dactylitis, enthesitis, and skin and nail involvement, are considered separately.

Psoriasis precedes the onset of PsA in 60%-80% of patients (sometimes by up to 20 years but usually by less than 10 years); but in as many as 15%-20% of patients, arthritis appears before psoriasis. On occasion, arthritis and psoriasis appear simultaneously.

Patients with PsA are typically seronegative for rheumatoid factor and antinuclear antibody; antinuclear antibody titers in persons with PsA do not differ from those of age- and sex-matched controls. C-reactive protein may be elevated but is often normal. Lack of C-reactive protein elevation, however, does not mean that systemic inflammation is absent but rather indicates that a different type of systemic inflammation may be at play for those patients.

Herbert S. Diamond, MD, Professor of Medicine (retired), Temple University School of Medicine, University of Pittsburgh; Chairman, Department of Medicine Emeritus, Western Pennsylvania Hospital, Pittsburgh, PA.

Herbert S. Diamond, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The diagnosis for this case is psoriatic arthritis (PsA). The 2018 American College of Rheumatology/National Psoriasis Foundation guidelines offer current treatment recommendations for this condition. For patients with active PsA who are treatment-naive, treatment recommendations are:

• Tumor necrosis factor (TNF) inhibitors are preferred over oral small molecules (OSMs), interleukin (IL)–17 inhibitors, or IL-12/23 inhibitors
• OSMs are recommended over IL-17 inhibitors or IL-12/23 inhibitors
• Methotrexate is recommended over nonsteroidal anti-inflammatory drugs
• IL-17 inhibitors are recommended over IL-12/23 inhibitors

Treatment recommendations for patients with active PsA despite the use of OSMs are: 

• Switching to a TNF inhibitor over another OSM, IL-17 or IL-12/23 inhibitors, abatacept, or tofacitinib
• Switching to an IL-17 inhibitor over another OSM, IL-12/23 inhibitor, abatacept, or tofacitinib
• Switching to an IL-12/23 inhibitor over another OSM, abatacept, or tofacitinib.

International groups, such as the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the European League Against Rheumatism (EULAR), have published treatment recommendations as well. These address both PsA and, to a lesser extent, psoriasis. The GRAPPA recommendations consider six domains of involvement (peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis, and nail psoriasis) and use a grid approach to account for various levels of disease activity and severity. The EULAR recommendations use an algorithmic approach that focuses mainly on musculoskeletal manifestations, specifically peripheral arthritis; manifestations, such as dactylitis, enthesitis, and skin and nail involvement, are considered separately.

Psoriasis precedes the onset of PsA in 60%-80% of patients (sometimes by up to 20 years but usually by less than 10 years); but in as many as 15%-20% of patients, arthritis appears before psoriasis. On occasion, arthritis and psoriasis appear simultaneously.

Patients with PsA are typically seronegative for rheumatoid factor and antinuclear antibody; antinuclear antibody titers in persons with PsA do not differ from those of age- and sex-matched controls. C-reactive protein may be elevated but is often normal. Lack of C-reactive protein elevation, however, does not mean that systemic inflammation is absent but rather indicates that a different type of systemic inflammation may be at play for those patients.

Herbert S. Diamond, MD, Professor of Medicine (retired), Temple University School of Medicine, University of Pittsburgh; Chairman, Department of Medicine Emeritus, Western Pennsylvania Hospital, Pittsburgh, PA.

Herbert S. Diamond, MD, has disclosed no relevant financial relationships.

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