What is the differential diagnosis for a patient presenting with a rash on the back, bilateral hip pain, and fatigue for one week?

Differential Diagnosis: Rash, Bilateral Hip Pain, and Fatigue for One Week

Immediate Life-Threatening Considerations

The combination of rash, bilateral hip pain, and fatigue for one week requires urgent evaluation for tickborne rickettsial diseases (particularly Rocky Mountain Spotted Fever), immune checkpoint inhibitor-related complications if on cancer therapy, and systemic inflammatory conditions like Still's disease. 1, 2

Critical Red Flags to Assess Immediately

• Temperature pattern: Document if fever is present, spiking (≥39°C suggests Still's disease), or continuous 2
• Rash morphology and evolution:
  • Petechial/purpuric rash with systemic toxicity suggests life-threatening infection (meningococcemia, Rocky Mountain Spotted Fever, bacterial endocarditis) 3, 1, 4
  • Maculopapular rash evolving to petechiae by day 5-6 is classic for Rocky Mountain Spotted Fever 1, 5
  • Salmon-pink transient rash coinciding with fever spikes suggests Still's disease 2
• Tick exposure history: Essential given the bilateral hip/back pain pattern which can indicate sacroiliitis in reactive arthritis from tickborne illness 1
• Cancer treatment history: Immune checkpoint inhibitors (anti-PD-1/PD-L1, CTLA-4 antagonists) can cause polymyalgia-like syndrome with severe proximal extremity pain, fatigue, and rash 1

Primary Diagnostic Categories

1. Tickborne Rickettsial Diseases

Rocky Mountain Spotted Fever must be excluded urgently as it presents with fever, fatigue, and characteristic rash beginning as blanching pink macules on ankles/wrists evolving to maculopapular with central petechiae by day 5-6, with back pain potentially indicating systemic involvement 1, 5

• Obtain blood cultures, serologic testing for RMSF, and PCR if available 1
• Start empiric doxycycline immediately if clinical suspicion is high - do not wait for confirmatory testing as delay increases mortality 1
• Thrombocytopenia and leukopenia support the diagnosis 1

Rat-bite fever can present with fever, maculopapular rash involving palms/soles appearing 2-10 days after exposure, and migratory polyarthralgia affecting large joints including hips 1, 6

• Inquire about rodent exposure (pet rats, wild rodents) 6
• Blood cultures for Streptobacillus moniliformis 6
• Untreated infection can result in death from sepsis or endocarditis 6

2. Immune Checkpoint Inhibitor-Related Toxicity (If Applicable)

If the patient is receiving cancer immunotherapy, immune-related adverse events are highly likely and present with polymyalgia-like syndrome, arthritis, or myositis 1

• Polymyalgia-like syndrome: Severe proximal upper/lower extremity myalgia with severe fatigue, bilateral hip pain without true weakness, highly elevated inflammatory markers (ESR, CRP), normal CK levels 1
• Immune-related arthritis: Can affect large joints including hips, may present with oligoarthritis and back pain suggestive of sacroiliitis, inflammatory markers very elevated 1
• Myositis: Presents with weakness (not just pain), markedly elevated CK, can be fatal if involves myocardium 1

Diagnostic workup:

• ESR, CRP (usually very elevated in ICPi-induced conditions) 1
• CK levels (normal in polymyalgia-like syndrome, markedly elevated in myositis) 1
• RF, anti-CCP, ANA (often negative but can be present) 1
• EMG and MRI if myositis suspected 1

3. Adult-Onset Still's Disease

Fever ≥39°C for ≥7 days with salmon-pink transient rash and arthralgia makes Still's disease a primary consideration 2

• Rash is erythematous, transient, coincides with fever spikes, preferentially involves trunk 2
• Can present with vasculitic purpuric rash in some cases 5, 2
• Bilateral hip involvement and back pain can occur 1

Essential laboratory workup:

• CBC with differential (neutrophilic leukocytosis expected) 2
• Inflammatory markers: CRP, ESR, ferritin (markedly elevated) 2
• IL-18 and calprotectin if available 2
• Monitor for macrophage activation syndrome (MAS): persistent fever, splenomegaly, rising ferritin, falling cell counts, abnormal liver function - this is life-threatening 2

4. Spondyloarthropathy with Reactive Features

Oligoarthritis of large joints with back pain suggestive of sacroiliitis can represent reactive arthritis following infection or as part of ankylosing spondylitis spectrum 1

• Patients can have conjunctivitis, urethritis, and back/hip pain 1
• Assess for inflammatory back pain features: morning stiffness, improvement with activity, worse at night 1
• BASDAI score and assessment of spinal mobility (modified Schober, occiput-to-wall distance) 1
• Inflammatory markers (ESR, CRP) and imaging (radiographs, MRI for sacroiliitis) 1

5. Intra-Articular Hip Pathology (Less Likely Given Bilateral Presentation)

Bilateral hip pain with systemic symptoms makes isolated intra-articular pathology less likely, but consider:

• Transient synovitis: More common in children 3-10 years, presents with hip pain 1-3 days, limping, low-grade fever (<37.5°C), ESR <20 mm/hr 7
• Septic arthritis: Must be excluded - severe pain on hip movement, fever >37.5°C, ESR ≥20 mm/hr, requires urgent hip aspiration 7
• Osteoarthritis, labral tears, femoroacetabular impingement typically present with anterior hip/groin pain without systemic symptoms 8, 9

Diagnostic Algorithm

Step 1: Immediate Assessment (Emergency Department if Systemically Ill)

• Vital signs including temperature pattern 2
• Complete blood count with platelet count 3
• Blood cultures if febrile 1, 3
• Inflammatory markers: ESR, CRP, ferritin 1, 2
• Coagulation profile if petechiae present 3

Step 2: Characterize the Rash

• Petechial/purpuric with systemic toxicity: Treat empirically for life-threatening infection (meningococcemia, RMSF, endocarditis) while awaiting cultures 3, 4
• Maculopapular evolving to petechiae: RMSF - start doxycycline immediately 1, 5
• Salmon-pink transient with fever spikes: Still's disease - obtain ferritin, consider rheumatology consultation 2

Step 3: Targeted History

• Tick exposure, outdoor activities, geographic location 1
• Rodent exposure 1, 6
• Cancer treatment history (immune checkpoint inhibitors) 1
• Duration and pattern of symptoms 2
• Associated symptoms: conjunctivitis, urethritis, morning stiffness 1

Step 4: Imaging

• Anteroposterior pelvis and lateral hip radiographs as initial imaging for hip pain 1
• MRI if inflammatory arthritis or sacroiliitis suspected 1
• Brain MRI if altered mental status develops 1

Common Pitfalls to Avoid

• Do not delay doxycycline if RMSF is suspected - waiting for confirmatory serology increases mortality as antibodies may not be detectable in acute phase 1
• Do not dismiss rash as benign dermatologic condition when accompanied by systemic symptoms - always consider life-threatening causes first 4
• Do not attribute symptoms solely to osteoarthritis in bilateral hip pain with systemic features - inflammatory conditions require different management 8, 9
• Do not miss immune checkpoint inhibitor toxicity - specifically ask about cancer treatment history as these complications can occur months after initiation 1
• Do not overlook macrophage activation syndrome in suspected Still's disease - monitor ferritin trends and cell counts closely 2