A 23-year-old man comes to the physician for frequent and painful urination. He has also had progressive painful swelling of his right knee over the past week. He is sexually active with two female partners and uses condoms inconsistently. His mother has an autoimmune disease that involves a malar rash. Examination shows conjunctivitis bilaterally. The right knee is warm, erythematous, and tender to touch; range of motion is limited. Laboratory studies show an erythrocyte sedimentation rate of 62 mm/h. Urinalysis shows WBCs. Further evaluation of this patient is most likely to reveal which of the following?

Recent norovirus gastroenteritis

Chondrocalcinosis of the left knee

A 27-year-old male presents to his primary care physician complaining of pain with urination and eye redness. He reports that he developed these symptoms approximately one week ago. He also has noticed left knee and right heel pain that started a few days ago. He denies any recent trauma. He had an episode of abdominal pain and diarrhea ten days ago that resolved. He has otherwise felt well. On exam, he walks with a limp and his conjunctivae are erythematous. Laboratory findings are notable for an elevated erythrocyte sedimentation rate (ESR) and elevated C-reactive protein (CRP). Which of the following is most likely associated with this patient’s condition?

Anti-cyclic citrullinated peptide (anti-CCP) antibody

A 22-year-old man comes to the physician for a follow-up evaluation for chronic lower back pain. He has back stiffness that lasts all morning and slowly improves throughout the day. He has tried multiple over-the-counter medications, including ibuprofen, without any improvement in his symptoms. Physical examination shows tenderness over the iliac crest bilaterally and limited range of motion of the lumbar spine with forward flexion. The results of HLA-B27 testing are positive. An x-ray of the lumbar spine shows fusion of the lumbar vertebrae and sacroiliac joints. The physician plans to prescribe a new medication but first orders a tuberculin skin test to assess for the risk of latent tuberculosis reactivation. Inhibition of which of the following is the most likely primary mechanism of action of this drug?

Inosine monophosphate dehydrogenase

A 42-year-old man presents to clinic complaining of increasing difficulty climbing stairs and standing up from sitting in his chair. On exam you perceive his strength to be 5/5 distally, but only 3/5 in proximal muscle groups bilaterally. There is a distinctive rash on his upper eyelids and around his eyes. Examination of the fingers is most likely to reveal which of the following?

Violaceous papules over the MCP and PIP joints

A 22-year-old woman presents to the emergency department with a 3-day history of fever and abdominal pain. She says that the pain is located in the left lower quadrant of the abdomen and feels crampy in nature. The pain has been associated with bloody diarrhea and joint tenderness. She has no past medical history but says that she returned 2 weeks ago from vacation in Asia where she tried many new foods. Her family history is significant for multiple cancers in close relatives. Physical exam reveals swollen ulcers on her legs, and colonoscopy reveals contiguous ulcerations from the rectum through the descending colon. Which of the following is associated with the most likely cause of this patient's symptoms?

Perinuclear anti-neutrophil cytoplasmic antibodies

A 32-year-old woman comes to her physician because of increasing back pain for the past 10 months. The pain is worse in the morning when she wakes up and improves with activity. She used to practice yoga, but stopped 5 months ago as bending forward became increasingly difficult. She has also had bilateral hip pain for the past 4 months. She has not had any change in urination. She has celiac disease and eats a gluten-free diet. Her temperature is 37.1°C (98.8°F), pulse is 65/min, respirations are 13/min, and blood pressure is 116/72 mmHg. Examination shows the range of spinal flexion is limited. Flexion, abduction, and external rotation of bilateral hips produces pain. An x-ray of her pelvis is shown. Further evaluation of this patient is likely to show which of the following?

High levels of creatine phosphokinase

High levels of rheumatoid factor

Presence of anti-dsDNA antibodies

Presence of anti-Ro and anti-La antibodies

Seronegative spondyloarthropathies for USMLE Step 1: High-Yield Internal Medicine Lessons

Overview - Backbone Blues, No RF Clues

Inflammatory arthritis of the axial skeleton (sacroiliac joints, spine).
Key features: inflammatory back pain (improves with exercise, worse with rest), enthesitis (inflammation at tendon insertions), and dactylitis (“sausage digits”).
Strongly associated with the HLA-B27 gene.
📌 Mnemonic PAIR: Psoriatic arthritis, Ankylosing spondylitis, IBD-associated arthritis, Reactive arthritis.

⭐ Seronegative means Rheumatoid Factor (RF) and anti-CCP antibodies are absent.

MRI of sacroiliitis in seronegative spondyloarthropathy

Ankylosing Spondylitis - Bamboo Spine, Aching Design

Chronic, inflammatory arthritis of the axial skeleton and sacroiliac joints; strong HLA-B27 association (>90%).
Presents in young men (<40y) with low back pain and morning stiffness that improves with activity.
Key findings: sacroiliitis, syndesmophytes, and eventual spinal fusion (“bamboo spine”).
Extra-articular features: anterior uveitis, aortitis, restrictive lung disease.
Tx: NSAIDs, physical therapy, TNF-α inhibitors (e.g., infliximab).

⭐ Restrictive lung disease in AS is due to chest wall fusion and ↓ mobility, not interstitial lung disease.

Psoriatic Arthritis - Silvery Scales, Sausage Nails

Asymmetric oligoarthritis, often with dactylitis (“sausage digits”) and enthesitis.
Skin precedes arthritis in 80% of cases; look for psoriatic plaques (silvery scales on an erythematous base).
Nail signs: Pitting, onycholysis, oil spots.
X-ray hallmark: “Pencil-in-cup” deformity of DIP joints.
Assoc: HLA-B27 (especially with axial disease).

Pencil-in-cup deformity in psoriatic arthritis

⭐ High-Yield: DIP joint involvement is classic for psoriatic arthritis, distinguishing it from Rheumatoid Arthritis.

Reactive Arthritis - Can't See, Can't Pee

Seronegative spondyloarthropathy triggered 1-4 weeks after a GU (Chlamydia) or GI (Salmonella, Shigella, Campylobacter) infection.
📌 Classic Triad: "Can't see, can't pee, can't climb a tree."
- Uveitis/Conjunctivitis: Can't see.
- Urethritis/Cervicitis: Can't pee.
- Asymmetric Oligoarthritis: Can't climb a tree (joint pain).
Also presents with enthesitis, dactylitis ("sausage digits"), and mucocutaneous lesions (keratoderma blenorrhagicum).

⭐ Strongly associated with HLA-B27.

Keratoderma blennorrhagicum on foot and swollen knee

Enteropathic Arthritis - Gut Feeling, Joint Squealing

Arthritis associated with IBD (Crohn's, Ulcerative Colitis).
Two patterns:
- Peripheral: Asymmetric, oligoarticular (≤4 joints), large joints. Arthritis activity often parallels gut flares.
- Axial: Sacroiliitis & spondylitis. Activity is independent of IBD activity; strong HLA-B27 association.
Extra-articular signs: Erythema nodosum, pyoderma gangrenosum, uveitis.

Erythema Nodosum on Shins

⭐ High-Yield: Treating the underlying IBD often improves peripheral arthritis, but axial (spinal) disease activity is independent of gut inflammation and may require separate targeted therapy.

Diagnosis & Management - Clues & Cures

Diagnosis:
- Clinical: Inflammatory back pain (improves with activity), enthesitis, dactylitis, uveitis.
- Labs: HLA-B27 (+), ↑ ESR/CRP. Seronegative (RF & ANA negative).
- Imaging: Sacroiliitis on X-ray or MRI. Advanced ankylosing spondylitis may show "bamboo spine."
Management:

⭐ While methotrexate helps peripheral arthritis in psoriatic arthritis, it is not effective for axial (spinal) disease in seronegative spondyloarthropathies. Use TNF-α inhibitors for that.

Hallmarks include HLA-B27 association, negative RF/ANA, and inflammatory axial arthritis.

Ankylosing Spondylitis leads to sacroiliitis and spinal fusion (bamboo spine).

Psoriatic Arthritis is linked to psoriasis, nail pitting, and pencil-in-cup deformities.

Reactive Arthritis triad: "can't see, can't pee, can't climb a tree" after a GI/GU infection.

Common features include enthesitis, dactylitis, and uveitis.

Treatment often involves NSAIDs and TNF-α inhibitors.

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