What are possible diagnoses for my symptoms, including fever, chills, night sweats, upper right quadrant pain, fatigue, brain fog, asymmetrical joint pain, muscle weakness, nausea, vomiting, hair loss, rashes, chest pain, flank pain, frequent infections, swollen hands, decreased appetite, tachycardia, decreased heart rate variability (HRV), constipation, and weight loss, with a positive antinuclear antibody (ANA) screen, speckled pattern, and titer value of 1:160, and negative tests for COVID-19, flu, RSV, mononucleosis, and normal liver function tests, complete blood count (CBC), and other laboratory results?

Differential Diagnosis for Prolonged Fever with Positive ANA and Multi-System Symptoms

Based on your constellation of symptoms—prolonged fever, positive ANA with speckled pattern at 1:160, upper right quadrant pain, asymmetric joint pain, constitutional symptoms, and weight loss—the most likely diagnoses to pursue are: (1) early undifferentiated connective tissue disease or evolving systemic lupus erythematosus (SLE), (2) adult-onset Still's disease, and (3) occult infection or malignancy that must be excluded first.

Priority: Rule Out Life-Threatening Conditions First

Your presentation demands immediate exclusion of serious conditions before attributing symptoms to autoimmune disease, as long COVID and autoimmune evaluations are diagnoses of exclusion 1.

Urgent Investigations Needed:

• Imaging for upper right quadrant pain (9 months duration): Abdominal ultrasound or CT to exclude hepatobiliary pathology, abscess, or malignancy 1
• Chest imaging: CT chest to evaluate for occult infection, malignancy, or interstitial lung disease given your chest pain and constitutional symptoms 1
• Blood cultures during fever spikes: To exclude endocarditis or occult bacteremia given your frequent infections 1
• Age-appropriate malignancy screening: Given 10% weight loss, night sweats, and fever—this triad suggests lymphoma or solid organ malignancy until proven otherwise 2

Understanding Your ANA Result

Your ANA titer of 1:160 with speckled pattern has limited diagnostic value in isolation 3. Research shows that in patients referred for positive ANA, only 9.1% have an actual ANA-associated rheumatic disease, and only 2.1% have lupus 3. No ANA-associated disease was identified in patients with titers <1:160 in referral populations 3.

However, your conversion from negative ANA 8 months ago to positive now, combined with your symptom complex, is more concerning than an isolated positive test 4, 5.

Key Point About ANA and Infections:

Positive ANA can occur with various infections, particularly intracellular organisms 5. The most common infectious causes include:

• Mycobacterium tuberculosis
• Treponema pallidum (syphilis)
• Orientia tsutsugamushi (scrub typhus)
• Bartonella henselae (cat scratch disease)
• HIV 5

Your positive EBV antibodies (though not acute) are relevant—one patient in a case series developed SLE after EBV infectious mononucleosis 5.

Most Likely Autoimmune Diagnoses to Pursue

1. Undifferentiated Connective Tissue Disease or Early SLE

Your symptom pattern suggests possible evolving lupus:

• Fever, fatigue, weight loss
• Asymmetric joint pain (arthralgia without clinical swelling can occur in early disease) 1
• Rashes (you mention rashes on tattoos—lupus can be photosensitive)
• Hair loss
• Positive ANA with speckled pattern 6

Next steps for SLE evaluation 6:

• Anti-dsDNA antibodies (by Farr radioimmunoassay, immunofluorescence on Crithidia luciliae, or ELISA for IgG)
• Anti-Smith antibodies (highly specific for SLE, though only 10% sensitive)
• Antinucleosome antibodies (ELISA)
• Complement levels (C3, C4—low in active SLE)
• Anti-SSA (Ro) and anti-SSB (La) (suggest lupus or Sjögren's syndrome)
• Urinalysis with microscopy (to detect nephritis)
• Complete metabolic panel to assess kidney and liver function 1

2. Adult-Onset Still's Disease (AOSD)

This diagnosis fits remarkably well with your presentation:

• Quotidian fever pattern (your fever escalated from 100-101°F to 101-102.5°F) 1
• Upper right quadrant pain (hepatomegaly/hepatitis occurs in AOSD)
• Rash (salmon-colored, evanescent rash is classic)
• Joint pain
• Weight loss
• Elevated ferritin (you mention ferritin is "in range"—but AOSD typically shows markedly elevated ferritin, often >1000 ng/mL) 1

Critical: One patient in a case series developed AOSD after scrub typhus infection 5, showing infection can trigger autoimmune disease.

Additional testing for AOSD:

• Ferritin level with glycosylated ferritin percentage (AOSD shows very high ferritin with low glycosylated fraction <20%)
• IL-6, IL-18 levels if available 1
• Repeat inflammatory markers during fever spike (your CRP is negative, which is unusual—consider checking during active fever)

3. Primary Sjögren's Syndrome

Less likely but possible given:

• Fatigue, brain fog
• Positive ANA
• Frequent infections (Sjögren's increases infection risk)

Testing: Anti-SSA (Ro), Anti-SSB (La), Schirmer test, salivary gland biopsy if indicated 6

Addressing Your Specific Symptom Clusters

Cardiovascular Symptoms (Tachycardia, Decreased HRV, Chest Pain)

Perform a 10-minute active stand test to assess for postural orthostatic tachycardia syndrome (POTS), which can occur with autoimmune conditions 1:

• Measure blood pressure and heart rate after 5 minutes supine
• Immediately upon standing
• At 2,5, and 10 minutes standing 1

Additional cardiac workup needed 1:

• ECG
• Echocardiogram (to exclude myocarditis or pericarditis)
• Troponin if chest pain is acute
• Consider ambulatory rhythm monitor

Gastrointestinal Symptoms (Nausea, Vomiting, Early Satiety, RUQ Pain)

Your 9-month history of RUQ pain requires imaging immediately 1. Possibilities include:

• Primary sclerosing cholangitis (PSC)—though more common with inflammatory bowel disease, can present with RUQ pain, fever, chills, night sweats 1
• Hepatic involvement from autoimmune disease
• Occult abscess or malignancy

Additional testing:

• Hepatitis panel (A, B, C)
• Autoimmune hepatitis markers (anti-smooth muscle antibody, anti-LKM)
• MRCP if PSC suspected 1

Neurological Symptoms (Brain Fog, Headache)

Consider CNS lupus or other autoimmune involvement 1:

• If severe headache or meningismus develops, lumbar puncture may be needed
• MRI brain if focal neurological symptoms develop

Common Pitfalls to Avoid

1. Do not assume positive ANA equals lupus—the positive predictive value is only 2.1% in unselected populations 3

2. Do not ignore the possibility of infection mimicking autoimmune disease—particularly with your history of frequent infections 5

3. Do not overlook malignancy—your B symptoms (fever, night sweats, weight loss) mandate cancer screening 2

4. Do not attribute everything to your existing diagnoses (PCOS, Hashimoto's, EDS)—these don't explain your acute deterioration 4

5. Your negative CRP is unusual for active inflammatory disease—consider checking during fever spike, or consider conditions where CRP may be normal despite inflammation 1

Recommended Immediate Action Plan

Week 1-2:

• Rheumatology referral (urgent) 2
• Abdominal imaging (ultrasound or CT) for RUQ pain 1
• Chest CT to exclude malignancy/infection 1
• Extended autoantibody panel: anti-dsDNA, anti-Smith, complement levels, anti-SSA/SSB 6
• Ferritin level with glycosylated fraction 1
• Blood cultures during next fever spike 1

Week 2-4:

• Hematology consultation if any cytopenias develop or if malignancy suspected 2
• Infectious disease consultation if imaging reveals abscess or if atypical infection suspected 5
• Cardiac evaluation with ECG, echo, active stand test 1

Your symptom duration (>12 weeks with progressive worsening) and multi-system involvement require aggressive diagnostic evaluation 1. The combination of constitutional symptoms, positive ANA, and organ-specific complaints suggests either evolving autoimmune disease or serious underlying pathology that must be identified promptly to prevent morbidity 2, 4.