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Causes of high C reactive protein (CRP)

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Related Subjects: |Ferritin |CEA |ESR |CRP |ALP |LDH |HbA1c |Alpha Fetoprotein |Anti-Hu ab |Biochemical Lab values

For poorly understood reasons the CRP is of no use as a useful guide of disease activity in Systemic lupus Erythematosus, Scleroderma, Ulcerative colitis and leukaemia

Overview of C-Reactive Protein (CRP)

C-reactive protein (CRP) is a substance produced by the liver in response to inflammation. It is part of the acute phase response, which is the body's early defense system against infections and injuries.
CRP levels in the blood increase rapidly in response to inflammation and decrease when the inflammation subsides, making it a useful biomarker for assessing inflammatory conditions and monitoring treatment responses.

Structure of C-Reactive Protein

Composition:
- CRP is a pentameric protein composed of five identical subunits, each containing 206 amino acids.
- These subunits form a cyclic, disc-shaped structure.
Binding Properties:
- CRP binds to phosphocholine expressed on the surface of dead or dying cells and some types of bacteria.
- This binding activates the complement system, promoting phagocytosis by macrophages and neutrophils.

Causes of Very high CRP

Cause	Clinical Features	Investigations	Management
Bacterial Infections (e.g., Sepsis, Pneumonia)	Fever, chills, tachycardia, hypotension, altered mental status, cough, difficulty breathing.	Blood cultures, complete blood count (CBC), chest X-ray, urine analysis, lactate levels, CRP, and procalcitonin levels.	Broad-spectrum antibiotics, intravenous fluids, supportive care, source control (e.g., drainage of abscess), monitoring in ICU if severe.
Severe Systemic Inflammatory Response (e.g., Acute Pancreatitis)	Severe abdominal pain, nausea, vomiting, fever, tachycardia, hypotension, jaundice.	Serum amylase and lipase levels, abdominal CT scan, CRP, liver function tests (LFTs), complete blood count (CBC).	Supportive care, intravenous fluids, pain management, enteral nutrition, monitoring for complications, surgical intervention if necessary.
Autoimmune Diseases (e.g., Rheumatoid Arthritis, Systemic Lupus Erythematosus)	Joint pain, stiffness, swelling, fatigue, malaise, skin rashes (e.g., malar rash in SLE), photosensitivity.	Autoantibody tests (e.g., RF, anti-CCP, ANA), CRP, ESR, joint imaging (e.g., X-ray, MRI), renal function tests if SLE is suspected.	Immunosuppressive therapy (e.g., methotrexate, corticosteroids), disease-modifying antirheumatic drugs (DMARDs), biological agents, monitoring for disease progression and complications.
Severe Viral Infections (e.g., COVID-19, Influenza)	Fever, cough, shortness of breath, myalgia, fatigue, anosmia (COVID-19), headache.	RT-PCR for viral RNA, chest imaging (X-ray, CT scan), CRP, CBC, liver function tests, oxygen saturation levels.	Supportive care, antiviral treatment if indicated (e.g., remdesivir for COVID-19), corticosteroids for severe cases, oxygen therapy, ICU care if severe.
Malignancies (e.g., Lymphoma, Solid Tumours)	Weight loss, fatigue, night sweats, lymphadenopathy, unexplained pain, or mass, fever.	CRP, CBC, imaging (CT, MRI, PET scans), biopsy of the suspicious lesion, tumour markers, bone marrow biopsy if hematological malignancy is suspected.	Chemotherapy, radiotherapy, surgical resection, targeted therapy, monitoring for response to treatment and complications.
Trauma or Major Surgery	Postoperative pain, swelling, erythema, fever, signs of infection or inflammation at the surgical site, delayed wound healing.	CRP, CBC, imaging (e.g., ultrasound, CT) if abscess or hematoma is suspected, wound cultures if infection is suspected.	Postoperative care, pain management, antibiotics if infection is suspected, wound care, surgical intervention if necessary for complications (e.g., abscess drainage).
Severe Burns	Pain, extensive skin damage, fluid loss, hypovolemic shock, infection, hypermetabolic state.	CRP, CBC, electrolytes, renal function tests, wound cultures if infection is suspected, blood gas analysis.	Fluid resuscitation, pain management, wound care, antibiotics if infection is present, nutritional support, monitoring in a burn unit.
Vasculitis (e.g., Giant Cell Arteritis, ANCA-associated Vasculitis)	Fever, weight loss, fatigue, headache (GCA), vision changes, muscle pain, joint pain, skin ulcers.	CRP, ESR, ANCA test (if suspected ANCA-associated vasculitis), temporal artery biopsy (for GCA), imaging (e.g., angiography), renal function tests.	Corticosteroids, immunosuppressive agents, monitoring for complications (e.g., aneurysms, renal failure), surgical intervention if necessary.
Adult Still's Disease	High spiking fevers, salmon-colored maculopapular rash, arthralgia, sore throat, lymphadenopathy, hepatosplenomegaly.	CRP, ESR, ferritin (often markedly elevated), CBC, liver function tests, autoantibody screen to exclude other conditions.	NSAIDs for symptom control, corticosteroids for severe cases, DMARDs (e.g., methotrexate), biological agents (e.g., IL-1 or IL-6 inhibitors), monitoring for complications like macrophage activation syndrome (MAS).

Functions of C-Reactive Protein

Acute Phase Response:
- CRP is one of the first acute-phase proteins to increase in response to inflammatory stimuli.
- Its levels can rise dramatically within 6-8 hours of the onset of inflammation, reaching a peak at around 48 hours.
Opsonization:
- CRP binds to the surface of pathogens and damaged cells, tagging them for destruction by the immune system.
- It enhances phagocytosis by acting as an opsonin.
Activation of Complement System:
- CRP activates the classical complement pathway, which contributes to the clearance of pathogens and dead cells.
Immune Modulation:
- CRP modulates the immune response by interacting with various immune cells, including macrophages and dendritic cells, influencing their activity and cytokine production.

Regulation of CRP Levels

Inflammatory Stimuli:
- CRP production is primarily regulated by pro-inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1 (IL-1), and tumour necrosis factor-alpha (TNF-α).
Acute Infections and Injuries:
- CRP levels increase significantly in response to acute bacterial infections, trauma, and tissue necrosis.
Chronic Inflammatory Conditions:
- Elevated CRP levels can be observed in chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus.

Clinical Significance

Diagnosis and Monitoring:
- CRP levels are measured to diagnose and monitor acute and chronic inflammatory conditions.
- High-sensitivity CRP (hs-CRP) assays can detect low levels of CRP, which are useful for assessing cardiovascular risk.
Cardiovascular Disease:
- Elevated CRP levels are associated with an increased risk of cardiovascular events, such as myocardial infarction and stroke.
- hs-CRP is used as a marker to evaluate cardiovascular risk in asymptomatic individuals.
Infections:
- CRP levels can help differentiate between bacterial and viral infections, as bacterial infections typically cause a more significant increase in CRP levels.
Inflammatory and Autoimmune Diseases:
- CRP is used to monitor disease activity and response to treatment in conditions like rheumatoid arthritis and lupus.
Surgical and Postoperative Monitoring:
- CRP levels can indicate postoperative complications, such as infections or anastomotic leaks.

Summary

C-reactive protein (CRP) is a key marker of inflammation produced by the liver in response to various inflammatory stimuli. It plays a crucial role in the acute phase response, opsonization, complement activation, and immune modulation. CRP levels are widely used in clinical practice to diagnose and monitor inflammatory conditions, assess cardiovascular risk, and evaluate infections and autoimmune diseases. Understanding the function and regulation of CRP is essential for its effective use in medical diagnostics and treatment monitoring.

PLEASE NOTE LEGAL ADVICE: The contents are under continuing development and improvements and may contain errors of omission or fact. Feedback vital and always welcome at drokane at gmail.com. This is not to be used for the assessment, diagnosis or management of patients. It should not be regarded as medical advice. It is only for educational purposes. Please adhere to your local protocols. If you are unwell please seek healthcare advice from your doctor. This does not replace senior or specialist advice. If you do not accept this then please do not use the website. If you need medical advice, please consult a doctor or other appropriate medical professional. If you are a medical professional and you need advice then speak to your senior or colleagues.

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