6.10 Other Primary Rheumatic Disorders & Mixed Connective Tissue Disease

ABIM Internal Medicine Exam

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1 Chapter 0: The ABIM Exam, Blueprint & Study Strategy

0.1 Exam Format, Question Types & the 2026 Blueprint 0.2 Eligibility, Registration, Fees & Exam-Day Logistics 0.3 Scoring, the Passing Standard & Score Reports 0.4 Building a Blueprint-Weighted Study Plan

2 Chapter 1: Cardiovascular Disease (14% of Exam)

1.1 Ischemic Heart Disease & Acute Coronary Syndromes 1.2 Antithrombotic Therapy, Secondary Prevention & Mechanical Complications of MI 1.3 Atrial Fibrillation, Atrial Flutter & Stroke Prevention 1.4 Supraventricular Tachycardias, Ventricular Arrhythmias & Bradycardias 1.5 Heart Failure: Classification, Staging & Guideline-Directed Medical Therapy 1.6 Device Therapy, HFpEF & the Cardiomyopathies 1.7 Valvular Heart Disease & Endocarditis Prophylaxis 1.8 Pericardial Disease & Acute Aortic Syndromes 1.9 Hypertension: Classification, Diagnosis & Secondary Causes 1.10 Hypertensive Crises & Dyslipidemia 1.11 Adult Congenital Heart Disease & Coarctation of the Aorta 1.12 Syncope: Reflex, Orthostatic & Cardiac Causes 1.13 Cardiac Physical Examination, Murmurs & Antithrombotic Selection

3 Chapter 2: Endocrinology, Diabetes & Metabolism (9% of Exam)

2.1 Diabetes Mellitus: Diagnosis, Glycemic Targets & Pharmacotherapy 2.2 Insulin Therapy, Hyperglycemic Emergencies & Chronic Complications 2.3 Thyroid Function Testing & Hypothyroidism 2.4 Thyrotoxicosis, Thyroid Storm & Thyroid Nodules 2.5 Adrenal & Pituitary Disorders 2.6 Hypercalcemia, Hypocalcemia & Disorders of Mineral Metabolism 2.7 Osteoporosis & Paget Disease of Bone 2.8 Ovarian, Testicular & Reproductive Endocrine Disorders 2.9 Hypoglycemia, Endocrine Tumors, Polyglandular Syndromes & Severe Hypertriglyceridemia

4 Chapter 3: Gastroenterology & Hepatology (9% of Exam)

3.1 Esophageal Disease 3.2 Stomach & Duodenal Disease and Gastrointestinal Hemorrhage 3.3 Inflammatory Bowel Disease 3.4 Celiac Disease & Irritable Bowel Syndrome 3.5 Diverticular Disease & Colorectal Cancer Screening 3.6 Viral Hepatitis, Steatotic & Alcohol-Associated Liver Disease 3.7 Cirrhosis & the Complications of Portal Hypertension 3.8 Acute Pancreatitis 3.9 Chronic Pancreatitis & Biliary Tract Disease 3.10 Inherited, Autoimmune & Drug-Induced Liver Disease 3.11 Small Intestinal Disease, Ischemia & Gastrointestinal Complications of HIV

5 Chapter 4: Infectious Disease (9% of Exam)

4.1 Lower Respiratory Tract Infections & Sepsis Syndromes 4.2 Viral Respiratory Pathogens & Tuberculosis 4.3 Central Nervous System Infections 4.4 Skin, Soft Tissue, Bone & Joint Infections 4.5 Infective Endocarditis & Cardiovascular Infection 4.6 Clostridioides difficile & Catheter-Related Bloodstream Infection 4.7 HIV Diagnosis, Antiretroviral Therapy & Prevention 4.8 Opportunistic Infections & Sexually Transmitted Infections 4.9 Fever of Unknown Origin, Neutropenic Fever & Toxic Shock 4.10 Travel-Related Illness, Vector-Borne Disease & Outbreaks 4.11 Infection Prevention, Nosocomial Infection & Postexposure Prophylaxis 4.12 Rheumatic Fever, Poststreptococcal Disease, Enteric & Hepatic Infections

6 Chapter 5: Pulmonary Disease (9% of Exam)

5.1 COPD: Diagnosis, GOLD Classification & Initial Pharmacotherapy 5.2 Interventions That Reduce COPD Mortality & Exacerbation Management 5.3 Asthma: Diagnosis, Stepwise Therapy & Status Asthmaticus 5.4 Interstitial Lung Disease & Idiopathic Pulmonary Fibrosis 5.5 Sarcoidosis, Hypersensitivity Pneumonitis & Occupational Lung Disease 5.6 Pulmonary Embolism: Diagnosis, Risk Stratification & Anticoagulation 5.7 Pulmonary Hypertension & Sleep-Disordered Breathing 5.8 Acute Respiratory Distress Syndrome & Mechanical Ventilation 5.9 Pleural Disease, Empyema & Pneumothorax 5.10 Bronchiectasis, Cystic Fibrosis & Restrictive Lung Disease 5.11 Evaluation of Cough, Dyspnea, Hemoptysis & the Solitary Pulmonary Nodule

7 Chapter 6: Rheumatology & Orthopedics (9% of Exam)

6.1 Rheumatoid Arthritis: Diagnosis & Systemic Manifestations 6.2 Antirheumatic Pharmacotherapy & the Spondyloarthropathies 6.3 Gout: Pathophysiology & Acute Management 6.4 Urate-Lowering Therapy & Calcium Pyrophosphate Deposition Disease 6.5 Osteoarthritis 6.6 Systemic Lupus Erythematosus 6.7 Systemic Sclerosis, Sjogren Syndrome & Inflammatory Myopathies 6.8 The Vasculitides 6.9 Regional Musculoskeletal Syndromes, Back Pain & Sports Injuries 6.10 Other Primary Rheumatic Disorders & Mixed Connective Tissue Disease 6.11 Osteonecrosis & Metabolic Bone Disease

8 Chapter 7: Hematology (6% of Exam)

7.1 Approach to Anemia & the Microcytic Anemias 7.2 Macrocytic, Normocytic & Hemolytic Anemias 7.3 Hemoglobinopathies, Thalassemias & Paroxysmal Nocturnal Hemoglobinuria 7.4 Platelet Disorders, Thrombocytopenia & the Bleeding Patient 7.5 Coagulation Factor Disorders, Thrombophilia & Anticoagulant Reversal 7.6 Acute Leukemias, Chronic Leukemias & Myeloproliferative Neoplasms 7.7 Lymphomas & Plasma Cell Disorders 7.8 Myelodysplastic Syndrome, Myeloproliferative Neoplasms & Porphyria 7.9 Transfusion Medicine & Late Complications of Transplantation

9 Chapter 8: Medical Oncology (6% of Exam)

8.1 Breast, Lung, Colorectal & Prostate Cancer 8.2 Oncologic Emergencies 8.3 Genitourinary & Gynecologic Malignancies 8.4 Head and Neck, Bone & Soft Tissue Cancer and Cancer of Unknown Primary 8.5 Complications of Cancer & Its Treatment 8.6 Cancer Prevention, Survivorship & Psychosocial Care

10 Chapter 9: Nephrology & Urology (6% of Exam)

9.1 Acute Kidney Injury: Staging, Etiology & Urine Microscopy 9.2 Glomerular Disorders & Nephrotic Syndrome 9.3 Nephritic Syndromes, RPGN & Indications for Renal Replacement Therapy 9.4 Chronic Kidney Disease: Staging & Progression Retardation 9.5 Complications of Chronic Kidney Disease: Anemia, CKD-MBD & Acidosis 9.6 Hyponatremia, Hypernatremia & Water Balance 9.7 Potassium Disorders & Systematic Acid-Base Analysis 9.8 Renal Tubular Acidosis & Nephrolithiasis 9.9 Prostate Disorders, Urinary Incontinence & Other Urologic Conditions 9.10 Cystic Kidney Disease, Obstructive Uropathy, Tubulointerstitial Disease & Hematuria

11 Chapter 10: Neurology (4% of Exam)

10.1 Acute Ischemic Stroke: Syndromes & Reperfusion 10.2 Transient Ischemic Attack, Secondary Prevention & Hemorrhagic Stroke 10.3 Headache & Facial Pain 10.4 Seizures, Epilepsy & Movement Disorders 10.5 Multiple Sclerosis & Neuromuscular Junction Disorders 10.6 Motor Neuron Disease & Acute Peripheral Neuropathy 10.7 Cranial Neuropathies & Neuro-Ophthalmology 10.8 Peripheral Neuropathies, CNS Tumors & Other Neurologic Disorders

12 Chapter 11: Psychiatry & Behavioral Health (4% of Exam)

11.1 Major Depressive Disorder & Medical Mimics 11.2 Antidepressant Pharmacotherapy & Treatment-Resistant Depression 11.3 Bipolar Disorder, Mood Stabilizers & Lithium Toxicity 11.4 Anxiety, Stress-Related & Obsessive-Compulsive Disorders 11.5 Alcohol Use Disorder & Withdrawal 11.6 Pharmacotherapy for Alcohol & Opioid Use Disorder 11.7 Toxidromes, Psychiatric Emergencies & Suicide Risk Assessment 11.8 Psychotic, Somatic Symptom, Factitious & Personality Disorders 11.9 Eating Disorders, Sleep Disorders & Sexual Health

13 Chapter 12: Dermatology (3% of Exam)

12.1 Dermatitis, Papulosquamous & Inflammatory Dermatoses 12.2 Acne, Rosacea & Cutaneous Infections 12.3 Herpes Zoster & Autoimmune Blistering Diseases 12.4 Nodules, Tumors & Cutaneous Oncology 12.5 Dermatologic Emergencies & Severe Cutaneous Adverse Reactions 12.6 Pigment Disorders, Alopecia, Nail Disease & Photosensitivity 12.7 Vascular Dermatoses, Environmental Injury & Cutaneous Signs of Systemic Disease

14 Chapter 13: Obstetrics & Gynecology / Women's Health (3% of Exam)

13.1 Contraception, Preconception Care & Teratogenicity 13.2 Hypertensive Disorders of Pregnancy & Gestational Diabetes 13.3 Thyroid Disease & Venous Thromboembolism in Pregnancy 13.4 Menopause & Menopausal Hormone Therapy 13.5 Abnormal Uterine Bleeding, Endometrial Disease & Gynecologic Cancer Screening 13.6 Breast Disorders & Diseases of the Vulva and Vagina 13.7 Menstrual Disorders, Fibroids, Endometriosis & Early Pregnancy Complications

15 Chapter 14: Geriatric Syndromes (3% of Exam)

14.1 Comprehensive Geriatric Assessment & Frailty 14.2 Falls, Gait Assessment & Polypharmacy 14.3 Urinary Incontinence & Pressure Injuries in Older Adults 14.4 Mild Cognitive Impairment, Dementia & Its Subtypes 14.5 Delirium & the Pharmacotherapy of Cognitive Disorders 14.6 Palliative Care, Hospice & Advance Care Planning 14.7 Chronic Wounds, Nutrition, Swallowing, Constipation & Hip Fracture 14.8 Sensory Impairment, Dizziness, Elder Mistreatment & Care Settings

16 Chapter 15: Allergy & Immunology (2% of Exam)

15.1 Anaphylaxis: Recognition & Emergency Management 15.2 Urticaria & Angioedema 15.3 Drug Allergy, Desensitization & Adult Immunodeficiency 15.4 Food Allergy, Insect Venom Hypersensitivity, Serum Sickness & Contrast Reactions 15.5 Rhinitis, Conjunctivitis, Eosinophilic & Mast Cell Disorders

17 Chapter 16: Preventive Medicine, Immunization & Clinical Epidemiology

16.1 The USPSTF Framework & Evidence-Based Cancer Screening 16.2 Cardiovascular & Metabolic Screening and Primary Prevention 16.3 Adult Immunization & Vaccines in Special Populations 16.4 Clinical Epidemiology, Biostatistics & Study Design

18 Chapter 17: Miscellaneous - Ethics, Patient Safety & Quality Improvement (2% of Exam)

17.1 Principles of Bioethics & Decisional Capacity 17.2 Informed Consent, Treatment Refusal & Special Scenarios 17.3 Surrogate Decision-Making, Advance Directives & Confidentiality 17.4 Patient Safety Science, Medical Error & Diagnostic Reasoning 17.5 Quality Improvement Methods, Health Disparities & Health Equity

19 Chapter 18: Perioperative Medicine & Medical Consultation

18.1 Preoperative Cardiovascular Risk Assessment 18.2 Preoperative Pulmonary Risk & Perioperative Medication Management 18.3 Perioperative Anticoagulation, Bridging & Postoperative Complications

20 Chapter 19: Ophthalmology (1% of Exam)

19.1 The Acute Red Eye & Ophthalmic Emergencies 19.2 Painless Vision Loss & Chronic Ophthalmic Disease 19.3 Uveitis, Scleritis & Orbital Disease

21 Chapter 20: Otolaryngology & Dental Medicine (1% of Exam)

20.1 Dizziness, Vertigo & Epistaxis 20.2 Ear Disorders, Hearing Loss & Upper Respiratory Infections 20.3 Oral Cavity, Salivary Gland, Laryngeal & Taste and Smell Disorders

6.10 Other Primary Rheumatic Disorders & Mixed Connective Tissue Disease

Key Takeaways Explain This Topic AI

Relapsing polychondritis, Behcet disease, fibromyalgia, adult Still disease, Marfan and Ehlers-Danlos syndromes and the arthropathy of hemochromatosis are enumerated under other primary rheumatic disorders.

Mixed connective tissue disease and Charcot-Marie-Tooth disease are separately named blueprint subsections under Rheumatology and Orthopedics.

Adult Still disease presents with quotidian spiking fever, an evanescent salmon-colored rash and a markedly elevated ferritin.

Relapsing polychondritis spares the earlobe because the process targets cartilage rather than soft tissue.

Mixed connective tissue disease is defined by a high-titer anti-U1 ribonucleoprotein antibody with overlapping lupus, scleroderma and myositis features.

Last updated: August 2026

1. Adult-Onset Still Disease

A systemic autoinflammatory disorder and a classic cause of fever of unknown origin in a young adult. The triad worth memorizing:

Quotidian fever — a daily spike, typically in the late afternoon or evening, returning to normal between spikes

Evanescent salmon-colored macular rash — appears with the fever spike and vanishes as it defervesces, so it is frequently absent when the patient is examined in the morning

Arthralgia or arthritis , plus sore throat , which is characteristic and often overlooked

Laboratory profile: marked leukocytosis with neutrophil predominance, elevated inflammatory markers, elevated aminotransferases, and a strikingly elevated ferritin — often over 1,000 and sometimes over 10,000 ng/mL. A low glycosylated ferritin fraction adds specificity. Rheumatoid factor and antinuclear antibody are characteristically negative , which is what separates it from rheumatoid arthritis and lupus.

It is a diagnosis of exclusion : infection, malignancy (especially lymphoma) and other autoimmune disease must be ruled out. Treatment ranges from NSAIDs through corticosteroids to interleukin-1 and interleukin-6 inhibition. The most feared complication is macrophage activation syndrome , signaled by a falling white count and platelet count with a rising ferritin and triglycerides in a previously inflamed patient.

2. Behcet Disease

A variable-vessel vasculitis most prevalent along the historic Silk Road — Turkey, the Middle East, Central and East Asia.

Cardinal features:

Recurrent oral aphthous ulcers — required for diagnosis, typically at least three episodes per year
Genital ulcers , which scar

Ocular disease — uveitis, classically posterior uveitis or panuveitis , and hypopyon; a leading cause of blindness

Skin lesions — erythema nodosum, pseudofolliculitis, acneiform nodules
Pathergy — a papule or pustule forming at a needle-prick site after 48 hours

Distinctive complications include venous thrombosis (treated with immunosuppression rather than anticoagulation alone), pulmonary artery aneurysm — a rare cause of hemoptysis in which anticoagulation is dangerous — and neuro-Behcet disease.

3. Relapsing Polychondritis

Immune-mediated inflammation of cartilage . The examination pearl is anatomic: auricular chondritis spares the earlobe , because the lobe contains no cartilage. A red, swollen, tender pinna with a normal lobe is nearly diagnostic.

Other features: saddle-nose deformity from nasal cartilage collapse, laryngotracheal involvement producing hoarseness, stridor and potentially life-threatening airway collapse, costochondritis, audiovestibular dysfunction, non-erosive arthritis, and aortic root dilation.

Airway involvement is what makes this dangerous and is the reason it cannot be managed as a purely cosmetic problem. It is associated with myelodysplastic syndrome in older patients, and treatment is corticosteroids with steroid-sparing immunosuppression.

4. Fibromyalgia

A disorder of central pain processing — not an inflammatory or autoimmune disease. Widespread pain of at least three months, with fatigue, unrefreshing sleep and cognitive difficulty ( fibro fog ). Inflammatory markers, complete blood count and imaging are normal ; abnormal results point to another diagnosis.

Management is heavily tested and counterintuitive : the intervention with the best evidence is graded aerobic exercise , alongside cognitive behavioral therapy and sleep hygiene. Pharmacotherapy is adjunctive — duloxetine, milnacipran, pregabalin or low-dose amitriptyline. Opioids and corticosteroids are ineffective and harmful. Coexisting fibromyalgia in a patient with rheumatoid arthritis or lupus explains persistent pain despite controlled inflammation, and the correct response is not to escalate immunosuppression.

5. Sjogren Syndrome

Lymphocytic infiltration of exocrine glands producing keratoconjunctivitis sicca and xerostomia . Diagnosis uses anti-Ro (SSA) and anti-La (SSB) antibodies, objective testing of tear production (Schirmer test) and salivary flow, and minor salivary gland biopsy when serology is negative.

Extraglandular disease includes interstitial lung disease, renal tubular acidosis (distal, type 1) , small-fiber neuropathy and cutaneous vasculitis.

Two facts that dominate exam items:

Markedly increased risk of non-Hodgkin lymphoma , particularly MALT lymphoma. Persistent unilateral parotid enlargement, new lymphadenopathy, a falling complement C4 or a new monoclonal gammopathy warrants evaluation for lymphoma.

Anti-Ro crosses the placenta and causes congenital heart block and neonatal lupus; pregnant patients require fetal monitoring.

6. Mixed Connective Tissue Disease

A separately enumerated blueprint subsection. Defined by a high-titer anti-U1 ribonucleoprotein (anti-RNP) antibody together with overlapping features of lupus, systemic sclerosis and inflammatory myositis.

Characteristic combination:

Raynaud phenomenon — nearly universal and usually the first symptom
Swollen sausage-like fingers (puffy hands) — a highly characteristic early sign
Arthritis, often more erosive than in lupus
Myositis with proximal weakness and elevated creatine kinase
Esophageal dysmotility

Pulmonary arterial hypertension — the leading cause of death, in contrast to lupus where renal and infectious causes dominate

Severe lupus nephritis and severe central nervous system disease are comparatively uncommon. Because pulmonary hypertension drives mortality, periodic echocardiographic screening is part of routine care. Over time, some patients evolve into a defined connective tissue disease.

Undifferentiated connective tissue disease describes patients with autoimmune features and autoantibodies who do not meet criteria for any specific disease; a substantial proportion never progress.

7. Marfan and Ehlers-Danlos Syndromes

Marfan syndrome — autosomal dominant FBN1 mutation affecting fibrillin-1.

System Features

Skeletal Tall stature, arachnodactyly, arm span exceeding height, pectus deformity, scoliosis, joint hypermobility, high-arched palate

Cardiovascular Aortic root dilation, dissection, aortic regurgitation, mitral valve prolapse
Ocular Ectopia lentis with superotemporal lens displacement
Pulmonary Spontaneous pneumothorax

Management centers on serial echocardiographic surveillance of the aortic root , beta-blockade or angiotensin receptor blockade to slow dilation, prophylactic aortic root replacement at a size threshold, and avoidance of isometric and contact sport. Pregnancy carries substantial dissection risk and requires pre-conception aortic assessment.

Ehlers-Danlos syndromes are a heterogeneous group with joint hypermobility, skin hyperextensibility and tissue fragility. The subtype that matters most is vascular Ehlers-Danlos syndrome (type IV) , caused by COL3A1 mutation, which produces spontaneous arterial, bowel and uterine rupture with thin translucent skin and easy bruising. It carries markedly reduced life expectancy, and arteriography and elective vascular procedures are hazardous because the vessels tear.

Contrast for the exam: lens dislocation is superotemporal in Marfan syndrome and inferonasal in homocystinuria; homocystinuria is autosomal recessive, causes intellectual disability and thrombosis, and is screened for biochemically.

8. Charcot-Marie-Tooth Disease

A separately named blueprint subsection despite being a hereditary neuropathy. The most common inherited peripheral neuropathy, usually autosomal dominant, commonly from PMP22 duplication.

Clinical signature:

Distal, length-dependent weakness and atrophy beginning in the feet — the classic inverted champagne bottle appearance of the legs

Pes cavus and hammer toes , often the presenting complaint and a strong clue to a long-standing hereditary process

Foot drop with a steppage gait
Absent ankle reflexes; comparatively mild sensory complaints
Slowly progressive over decades , with a positive family history

Demyelinating forms show uniformly slowed conduction velocities on nerve conduction studies; axonal forms show reduced amplitudes. Diagnosis is confirmed genetically. There is no disease-modifying therapy; management is bracing, physical therapy and orthopedic care. Neurotoxic drugs — vincristine in particular — must be avoided , since they can precipitate severe, irreversible deterioration.

9. Arthropathy of Hemochromatosis and Scoliosis

Hemochromatosis arthropathy classically affects the second and third metacarpophalangeal joints — an unusual distribution that should prompt iron studies. It resembles osteoarthritis radiographically with hook-like osteophytes, is frequently associated with chondrocalcinosis and calcium pyrophosphate deposition , and characteristically does not improve with phlebotomy even when systemic iron overload is corrected.

Scoliosis in adults matters when the Cobb angle is large enough to produce restrictive lung disease and, in extreme cases, chronic hypercapnia and cor pulmonale.