HYPERSENSITIVITY REACTIONS
Immune system vs. the body
Hypersensitivity reactions (HSRs) refers to autoimmunity, the process where the body’s immune system mistakenly attacks itself. There are four different types of HSRs, each with a different fundamental mechanism. These are very high yield!
AUTOANTIBODIES
Autoantibodies are antibodies that attack its own host.
They are present in all rheumatological diseases.
Each disease's most specific test is bolded.
Mixed Connective Tissue Disorder has features of multiple different rheumatologic disorders, including Lupus, Scleroderma and polymyositis. It’s associated with the anti-U1 RNP autoantibody.
SYSTEMIC LUPUS ERYTHEMATOSUS
“It’s never lupus” -House
Systemic Lupus Erythematosus (SLE), or simply Lupus, is an autoimmune condition defined by an abundance of autoantibodies that shower the body and cause widespread problems. The essence of Lupus is that the immune system begins to attack nucleic acids. DNA and RNA are normally sequestered away from the immune system inside of cells, but every time a cell dies (either necrosis or apoptosis), some of its DNA and RNA spills into the blood, kickstarting inflammation. The apoptosis phenomenon explains why the Lupus rash gets worse when exposed to sunlight, because UV radiation damages skin cells and leads to apoptosis. Lupus tends to affect young adult women of child bearing age (9 to 1 ratio of women to men).
What are the symptoms of Lupus?
Lupus falls on a wide spectrum of symptoms. Some patients have all the symptoms, others only have a few. The most common symptoms are rashes, arthritis, hematologic abnormalities, low grade fever and fatigue. Lupus can cause a lot of different rashes, but the classic rash is a malar rash in a butterfly distribution on the face that worsens with sunlight -- this rash spares the nasolabial folds, unlike seborrheic dermatitis. Over half of patients develop from kidney problems. Lupus can cause both nephritic and nephrotic syndromes (see Lupus Nephritis page in the Renal section). Other symptoms include pleuritis, pericarditis, Raynaud’s and oral ulcers. In severe cases of Lupus, the brain gets inflamed (encephalitis), which carries a poor prognosis.
How do you diagnose Lupus?
It’s tricky and subjective. There are a list of 11 major findings, and a person is said to have Lupus if they have 4 or more of these. To help with the diagnosis, the presence of autoantibodies can be helpful. Antinuclear antibodies (ANAs) are a collection of different antibodies that attack different parts of the nucleus, and they are usually (95%) elevated in Lupus; however, many other autoimmune conditions have high ANAs as well. If you attach a fluorescent marker to them, ANA patterns can be inspected under the microscope (fluoroscopy) to improve the specificity of the ANA. The most specific tests are the anti-double-stranded DNA and the anti-sRNP (or Smith) -- these pretty much clinch the diagnosis . The dsDNA antibody tends to correlate with kidney damage.
How do you treat Lupus?
Long term treatment mostly consists of anti-inflammatory and immunosuppressive drugs like Hydroxychloroquine or one of the new monoclonal antibodies. The treatment of acute flare ups consists of steroids.
What is Neonatal Lupus?
Since Lupus usually occurs in young adult women, it’s common for Lupus to overlap with pregnancy. In some cases of Lupus, the mom’s autoantibodies will cross the placenta into the baby and wreak havoc. The classic buzzword symptoms are a type 3 AV block plus circular rashes. The Sjögren autoantibodies, which are directed against the Ro (SSA) and La (SSB) nucleoproteins, tend to be elevated in neonatal Lupus.
What is Lupus Antiphospholipid Syndrome?
Lupus Antiphospholipid Syndrome is a clotting disorder seen in about 10% of Lupus patients. The patient’s immune system pumps out autoantibodies against phospholipids, which somehow leads to both arterial and venous blood clots, but the mechanism is not well understood. Clumps of phospholipids also can clump together as vegetations on cardiac valves -- interestingly these growths can be seen on both sides of a valve (atrial side and ventricular side, for the mitral valve). Medical laboratories use phospholipids for some of their tests, and in Lupus Antiphospholipid Syndrome some of these tests have false positive results. Several syphilis tests like RPR and VDRL will come back positive. The PTT will be prolonged, which is a bit paradoxical if you think about it.
What is drug-induced Lupus?
Several drugs will temporarily induce Lupus-like symptoms. This includes hydralazine, procainamide, isoniazid, penicillamine and anti-TNF antibodies. Patients generally experience mild arthralgias, fatigue, pleuritis and pericarditis -- but generally don’t get the classic rash. The anti-histone autoantibody is typically elevated. Symptoms go away when you stop the drug.
Malar rash in a butterfly shape
SJÖGREN SYNDROME
Dryness disease
Sjögren Syndrome is an autoimmune attack on salivary glands and tear ducts, causing dry eyes (keratoconjunctivitis) and dry mouth (xerostomia). This combination of symptoms was historically called “sicca.” The cause isn’t known, but likely involves a combination of T and B cells attacking the exocrine glands of salivary and lacrimal glands. We know that lymphocytes are heavily involved, because we can visualize huge swarms of them under the microscope. If these crazed proliferating lymphocytes are not stopped, there is a strong likelihood of a progression to lymphoma (40x increased risk), especially marginal zone lymphoma.
This rheumatological disease is most commonly seen in women in their 50s and 60s. Dry eyes are horribly uncomfortable, and will require treatment with artificial tears. The xerostomia can lead to a few different complications, which highlight the important role that saliva plays in healthy people. Saliva naturally contains antibiotic and pro-dental properties, which is why dental caries are a common phenomenon. The parotid glands are commonly involved, which can give patients swollen chipmunk-like cheeks. One-third of patients suffer from extraglandular disease, which can cause serositis, arthropathy and neuropathy.
The symptoms of Sjögren are pretty distinct, you shouldn’t have too much trouble recognizing it. You can look for elevated levels of autoantibodies targeted against the Ro (SS-A) and La (SS-B) ribonucleoproteins, which are elevated in about 90% of cases. In pregnant patients, these antibodies can cross the placenta and cause neonatal Lupus. A lip biopsy is needed to definitively diagnose.
SCLERODERMA
Autoimmune fibroblast disease
Scleroderma is an autoimmune disease that is characterized by overactivation of fibroblasts, which leads to the creation of way too much connective tissue all over the body. Too much collagen can interrupt normal bodily functions (block neurons, occlude vessels, interrupt muscles, etc.). The cause and mechanism are not well known. Scleroderma nearly always begins with skin symptoms. It turns your skin thick, or sclerotic. It usually hits the hands first, causing Raynaud's phenomenon, or cold temperature-induced finger hypoperfusion and pallor. Sclerosis of the skin will spread and worsen over time. It can lead to claw-shaped hands and a shrunken, pursed facial appearance.
In Limited Scleroderma, the symptoms progress more slowly and mostly remain limited to the skin. It has a much better prognosis. Some will develop a handful of predictable symptoms, called CREST syndrome. CREST stands for Calcinosis, Raynaud’s, Esophageal dysmotility, Sclerodactyly and Telangiectasia. Pulmonary hypertension may also occur. CREST syndrome is associated with high levels of anti-Centromere autoantibodies.
Calcinosis - hard calcium nodules that form under the skin
Raynaud’s - episodic finger hypoperfusion
Esophageal dysmotility - connective tissue deposition in the esophagus impairs neuron signaling, leading to dysphagia
Sclerodactyly - a claw-like pattern of skin sclerosis of the hands. May result in finger ulcers.
Telangiectasia - spider web-like vascular formations on the skin
In Systemic Scleroderma, the disease swiftly spreads to multiple organs. It carries a much worse prognosis. Nearly every organ in the body can be affected, and the presentation can vary significantly between different patients. The kidney is frequently hit, leading to nonspecific patterns of CKD, proteinuria and hypertension. In some cases it can follow an acute, rapid and malignant course (scleroderma renal crisis) treated with ACE inhibitors. Lung involvement may cause interstitial fibrosis and pulmonary hypertension. Gut involvement can lead to esophageal dysmotility. Heart involvement can lead to pericarditis, myocardial fibrosis and coronary artery disease. Systemic Scleroderma is associated with high levels of anti-DNA topoisomerase I (anti-Scl 70) autoantibody.
Sclerodactyly (claw hand)
Skin sclerosis affecting the finger
