What are possible diagnoses for my symptoms, including fever, chills, night sweats, upper right quadrant pain, fatigue, joint pain, muscle weakness, nausea, vomiting, hair loss, and weight loss, with lab results showing a positive Antinuclear Antibody (ANA) screen, speckled pattern, and titer value of 1:160, and a history of Hashimoto's (hypothyroidism) and Hypermobile Ehlers Danlos Syndrome?

Differential Diagnosis for Your Symptom Complex

Based on your positive ANA (1:160, speckled pattern), prolonged fever, constitutional symptoms, and existing autoimmune conditions, you should be evaluated urgently for systemic lupus erythematosus (SLE), adult-onset Still's disease, and undifferentiated connective tissue disease, while also investigating for occult malignancy and chronic infection given the 9-month duration of upper right quadrant pain and progressive weight loss.

Primary Diagnostic Considerations

Systemic Lupus Erythematosus (SLE)

• Your ANA titer of 1:160 with speckled pattern is significant and warrants further autoimmune workup, as high titers (>1:160) suggest the presence of connective tissue disease 1
• The combination of fever, joint pain, fatigue, hair loss, weight loss, and positive ANA strongly suggests SLE as a leading diagnosis 1
• Critical next steps: You need testing for anti-dsDNA, anti-Sm, complement levels (C3, C4), and complete ENA panel to confirm or exclude SLE 1
• Your existing Hashimoto's thyroiditis increases the likelihood of additional autoimmune disease, as 30% of ANA-positive patients have thyroid antibodies and multiple autoimmune conditions frequently coexist 2

Undifferentiated Connective Tissue Disease (UCTD)

• Your symptom constellation (Raynaud's-like symptoms with hand swelling, joint pain, fatigue, sicca symptoms implied by your presentation) with positive ANA but without meeting full SLE criteria may represent UCTD 3
• Notably, patients with hypermobile Ehlers-Danlos Syndrome have high rates of ANA positivity (62% in one study) with speckled pattern being most common (73%), often without identifiable specific nuclear antigens 3
• However, your progressive systemic symptoms (fever, weight loss, organ involvement) suggest this is more than just ANA positivity associated with hEDS 3

Adult-Onset Still's Disease

• Your quotidian fever pattern (daily spiking fevers), joint pain, and constitutional symptoms are classic for Still's disease 1
• The absence of elevated CRP and normal ESR makes this less likely but does not exclude it, as some patients have normal inflammatory markers early in disease 1
• Ferritin level should be checked urgently—markedly elevated ferritin (>1000 ng/mL) with low glycosylated ferritin fraction is highly suggestive 1

Secondary Considerations Requiring Urgent Evaluation

Occult Malignancy

• Your 9-month history of upper right quadrant pain, progressive weight loss (10% in 6 months), night sweats, and fever mandates imaging to exclude hepatobiliary or pancreatic malignancy 1
• Patients with metabolic syndrome features (PCOS) have higher risk of cholangiocarcinoma and hepatocellular carcinoma 1
• Immediate imaging needed: Abdominal CT or MRI with contrast to evaluate liver, gallbladder, pancreas, and lymph nodes 1
• Consider age-appropriate cancer screening including colonoscopy given constitutional symptoms 1

Chronic Infection

• Despite negative acute infection testing, chronic infections can present with your symptom pattern 1
• Fever without identified source for >1 month requires: Blood cultures (if not already done), HIV testing, tuberculosis screening (QuantiFERON or PPD), and consideration of endemic fungi depending on geographic exposure 1
• Your history of "frequent infections for 12 months" raises concern for underlying immunodeficiency—check immunoglobulin levels (IgG, IgA, IgM) and lymphocyte subsets 1

Autoimmune Hepatitis (AIH)

• Your upper right quadrant pain for 9 months with positive ANA (speckled pattern) raises concern for autoimmune hepatitis, even though your liver function tests are currently normal 1
• ANA positivity occurs in 80% of Type 1 AIH patients, and speckled pattern is common 1
• However, normal ALT/AST makes active AIH less likely—AIH typically presents with elevated transaminases 1
• Consider checking anti-smooth muscle antibodies (SMA), anti-SLA/LP, and total IgG levels 1
• Important caveat: In NASH patients, ANA ≥1:160 occurs in 21% without AIH, but you don't have documented NASH 1

Thyroid-Related Considerations

Hashitoxicosis or Thyroid Dysfunction

• Your Hashimoto's thyroiditis can have variable presentations including transient hyperthyroid phases (hashitoxicosis) that cause fatigue, weight loss, and elevated heart rate 4
• Check current TSH, free T4, and free T3 to ensure your thyroid is truly "well controlled" 5, 6
• Paradoxically, both hypothyroidism and hyperthyroidism can cause fatigue 6
• Your positive ANA is expected with Hashimoto's—47% of Hashimoto's patients are ANA positive, most commonly with titers of 1:40 7

Critical Diagnostic Algorithm

Immediate Laboratory Testing (Within 1 Week)

1. Complete autoimmune panel: Anti-dsDNA, anti-Sm, complement C3/C4, complete ENA panel (SSA, SSB, RNP, Scl-70) 1
2. Inflammatory markers: Repeat CRP (high-sensitivity), ESR, ferritin with glycosylated ferritin fraction 1
3. Liver evaluation: Comprehensive metabolic panel, anti-smooth muscle antibodies, total IgG 1
4. Infection screening: Blood cultures, HIV, QuantiFERON-Gold, hepatitis panel if not recent 1
5. Immunology: Immunoglobulin levels (IgG, IgA, IgM), lymphocyte subsets 1
6. Current thyroid status: TSH, free T4, free T3 5, 6

Immediate Imaging (Within 1-2 Weeks)

1. Abdominal CT with IV contrast or MRI: To evaluate upper right quadrant pain, assess for hepatobiliary pathology, lymphadenopathy, or occult malignancy 1
2. Chest X-ray: To evaluate for pulmonary involvement, lymphadenopathy, or infection 1

Specialist Referrals

1. Rheumatology (urgent): For evaluation of possible SLE or other connective tissue disease given positive ANA with systemic symptoms 1
2. Gastroenterology/Hepatology: For persistent upper right quadrant pain evaluation 1
3. Infectious Disease: If initial infection workup is unrevealing but fever persists 1

Important Clinical Pitfalls

• Do not dismiss your ANA as simply related to Hashimoto's or hEDS when you have progressive systemic symptoms including fever, weight loss, and organ-specific pain 1, 3
• Fever is rare in idiopathic pulmonary fibrosis and most autoimmune conditions without active inflammation—its presence suggests active systemic disease or infection 1
• Normal inflammatory markers (CRP, ESR) do not exclude serious autoimmune disease or malignancy—some patients have seronegative or marker-negative disease 1
• Your 10% weight loss in 6 months is a red flag that requires aggressive investigation regardless of other findings 1
• The 9-month duration of upper right quadrant pain requires imaging—gallstone disease, biliary pathology, and hepatic/pancreatic tumors must be excluded 1

Prognosis Context

Without treatment, severe autoimmune hepatitis has 40% mortality within 6 months, and untreated SLE can cause irreversible organ damage 1. Your constellation of symptoms warrants urgent, comprehensive evaluation rather than watchful waiting.