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- Kidney damage and kidney failure

- Headache, dizziness, vision problems and even strokes & seizures

- Anemia & increase risk of bleeding or blood clotting

- Increase chances of developing inflammation of chest cavity lining & pneumonia (An infection that inflames the air sacs in one or both lungs)

- Inflammation of the heart muscle

- Miscarriage in pregnant women

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- More common in women,
- Most often diagnosed in people between the age of 15 and 45 (Affects all age groups)
- More common in African Americans, Hispanics, and Asian Americans

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Erythema is an abnormal redness of skin or mucous membranes. The most common type of erythema is erythema multiforme (EM) which is caused by the deposition of IgM immune complexes in the skin, due to viral infections

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*Patient has a high blood pressure, leads to stage 2 hypertension

*Patient’s heart rate is normal

*Patient’s respiratory rate is high

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i) Complete blood count: To measure the number of red blood cells, white blood cells and platelets as well as the amount of haemoglobin.

ii) Erythrocyte sedimentation rate: This blood test determines the rate at which red blood cells settle to the bottom of a tube in an hour. A faster than normal rate may indicate a systemic disease, such as lupus.

iii) Urinalysis: Examines a sample of your urine which may show an increased protein level or red blood cells in the urine, which may occur if lupus has affected your kidneys

iv) Antinuclear antibody (ANA) test: A blood test that looks for antinuclear antibodies in your blood. A positive ANA test indicates the patient may have lupus. Some who test positive may not have lupus. Therefore, if there is a positive test for ANA, doctor may advise more-specific antibody testing

v) Kidney biopsy: The most definitive test for diagnosing lupus nephritis. A test where the doctor removes a small section of kidney tissue for lab analysis.

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1. Rhinitis, or the common cold
-sneezing
-scratchy throat
-runny nose
-children may experience low fever
-patients with asthma and other respiratory conditions such as COPD often suffer severe symptoms

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3. Otitis media
-pain in ear and loss of hearing
-children may experience: irritability, fussiness, difficulty in sleeping, eating or hearing

severe or untreated infection: leads to rupture of eardrum because of the pressure of pus buildup, or to internal breakthrough of these infected fluids, which can lead to more serious conditions such as mastoiditis, meningitis or intracranial abscess.

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Diseases related to Staphylococcus aureus

1. Rhinitis, or the common cold
- caused by 200+ kinds of viruses
- Viral infection can predispose patients to secondary infections by other microorganisms, such as bacteria. Secondary infections may explain why some people report that their colds improved when they were given antibiotics. (The cold was caused by viruses; bacteria infection may have followed.)

2. Sinusitis
- caused by various bacteria and fungi (exp: streptococcus pneumononiae, streptococcus pyogenes, staphylococcus aureus, and Haemophilus influenza)

3. Acute Otitis Media (Ear Infection)
- caused by Streptococcal pneumoniae, Haemophilus influenza and other bacteria
- Viral infections of the upper respiratory tract lead to inflammation of the eustachian tubes and the buildup of fluid in the middle ear, which can lead to bacterial multiplication in those fluids. The presence of bacteria increases the inflammatory response, leading to pus production.

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Dyspigmentation is an abnormality in the formation of pigmentation in the skin, clinically due to, hyperpigmentation (too much pigmentation) or hypopigmentation (too little pigmentation).

The possible cause of dyspigmentation is due to the medications taken by the patient. Medications that can trigger dyspigmentation are chemotherapy drugs, antibiotics, antimalarials & anti-seizure drugs.

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Nonsteroidal anti-inflammatory drugs (NSAIDs)

E.g. Naproxen sodium (Aleve) and Ibuprofen (Advil, Motrin IB, others)
MOA: inhibit both COX enzymes, thus decreasing prostaglandin production throughout the body as a result of which inflammation, pain, and fever are reduced
Therapeutic uses: treat pain, swelling and fever associated with lupus (Reduce pain and inflammation)
Side effects: stomach bleeding, kidney problems and an increased risk of heart problems.
Contraindications:
1. Asthmatic patients
2. During the third trimester of pregnancy
3. Patients with impaired renal function
4. Patients who have experienced an allergic reaction (urticaria, asthma, etc.) after taking NSAIDs
5. Patients with peptic ulcer disease
6. Patients with coagulation problems

Antimalarial drugs

E.g. Hydroxychloroquine (Plaquenil)
Therapeutic Uses: treat malaria, affect the immune system, help decrease the risk of lupus flares.
Side effects: stomach upset and, very rarely, damage to the retina of the eye.
Regular eye exams are recommended when taking these medications.
Contraindications:

hypoglycaemia

glucose-6-phosphate dehydrogenase (G6PD) deficiency

low amount of magnesium in the blood

low amount of potassium in the blood

anemia

decreased blood platelets

low levels of a type of white blood cell called neutrophils

mental problems

chronic heart failure

liver problems

decreased kidney function

Corticosteroids.

E.g. Prednisone, methylprednisolone (Medrol)
Therapeutic Uses: counter the inflammation of lupus, control serious disease that involves the kidneys and brain
Side effects: weight gain, easy bruising, thinning bones, high blood pressure, diabetes and increased risk of infection.
The risk of side effects increases with higher doses and longer term therapy.
Contraindications:

herpes simplex infection of the eye

an infection due to a fungus

an infection

a condition with low thyroid hormone levels

diabetes

high cholesterol

low amount of potassium in the blood (hypokalaemia)

psychotic disorder

brain injury

myopathy

cataracts (clouding of the lens of the eye)

hypertension

chronic heart failure

Immunosuppressants

E.g. Azathioprine (Imuran, Azasan), mycophenolate (Cellcept), Methotrexate (Trexall, Xatmep, others), Cyclosporine (Sandimmune, Neoral, Gengraf) and Leflunomide (Arava)
MOA (Cyclosporine): inhibit the production of cytokines involved in the regulation of T-cell activation, inhibit the production of NFAT1 transcription factor by calcineurin
Therapeutic Uses: suppress the immune system (may be helpful in serious cases of lupus)
Side effects: Increase the risk of infection, liver damage, decreased fertility and an increased risk of cancer.

Biologics.

E.g. Belimumab (Benlysta) i.v. route
MOA: Belimumab is a recombinant, fully human, monoclonal antibody directed against the B-cell activating factor (BAFF). It plays a central role in B-cell survival and function. Elevated circulating BAFF levels are common in SLE patients. Therefore, inhibiting the biological activity of BAFF is potentially helpful in the treatment of the disease.
Therapeutic Uses: reduces lupus symptoms in some people.
Side effects: nausea, diarrhea and infections. Rarely, worsening of depression can occur.
Contraindications:

anaphylaxis to belimumab

suicidal thoughts

depression

brain infection

E.g. Rituximab (Rituxan, Truxima) i.v.r oute
may be beneficial for some people in whom other medications haven't helped.
MOA: Anti CD20 chimeric antibody with human IgG1 immunoglobulin. CD20 plays a role in the maturation and activation of B cells. The mechanism of action of rituximab in autoimmune disease is disrupting B cells' function in the immune system and decrease in plasma cell production of CD20.
Therapeutic Uses: decrease joint pain and swelling
Side effects: allergic reaction to the intravenous infusion and infections.
Contraindications:

Severe infection

Hypersensitivity to any of the components of the formulation

Severe heart failure

Uncontrolled cardiac disease

Pregnancy

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When the stain combines with bacteria in a sample, the bacteria will either stay purple or turn pink or red.

If the bacteria stays purple, they are Gram-positive. If the bacteria turns pink or red, they are Gram-negative

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DMARDS, Immunomodulators

Disease-modifying antirheumatic drugs (DMARDS) are immunomodulatory agents that act as immunosuppressives and cytotoxic and anti-inflammatory medications.

Azathioprine, mycophenolate, and cyclosporine have all been studied for lupus manifestations such as nephritis.

Mycophenolate is useful for maintenance in lupus nephritis and other serious lupus cases. This agent inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Mycophenolate also inhibits antibody production.
Mechanism of Action

-Inhibits T- and B-cell proliferation, as well as antibody production

-Acts as noncompetitive, selective, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH)

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Antimalarials

Antimalarial agents may work through numerous proposed mechanisms in SLE, mediating subtle immunomodulation without causing overt immunosuppression.

These drugs are useful in preventing and treating lupus skin rashes, constitutional symptoms, arthralgias, and arthritis; antimalarials also help to prevent lupus flares and have been associated with reduced morbidity and mortality in SLE patients

Hydroxychloroquine sulfate (Plaquenil)

-inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions.

-This agent is also commonly used for suppression and treatment of malaria. Mechanisms underlying the anti-inflammatory and immunomodulatory effects of hydroxychloroquine are unknown

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Corticosteroids

Corticosteroid agents are used predominantly for anti-inflammatory activity and as immunosuppressants.

Prednisone is an immunosuppressant for the treatment of autoimmune disorders.
It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear neutrophil activity.

Prednisone stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.

Low-dose oral prednisone can be used for milder SLE, but more severe involvement necessitates high doses of oral or intravenous therapy.

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The two types of bacteria that cause most cases of cellulitis are Staphylococcus (staph) and Streptococcus (strep). Both can live harmlessly on intact skin, but when the skin is broken, the result can be a bacterial infection of the top or deeper layers of the skin.

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Signs and symptoms of cellulitis include swelling, redness, pain, and tenderness in the affected area. Some people also develop blisters, chills, fevers, and nausea.

Cellulitis is treatable with antibiotics. But if it goes untreated, the infection can get into the bloodstream and become life-threatening.

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• Genetic Factors –

1. Family members of patients have an increased risk of developing SLE (20% of clinically unaffected first-degree relatives of SLE patients reveal autoantibodies and other immunoregulatory abnormalities)

2. Hi3. HLA associations – HLA-DQ locus have been linked to the production of anti-double-stranded DNA, anti-Sm, and antiphospholipid antibodies

4. Inherited deficiencies of early complement components, such as C1q , C2 or C4

5. Polymorphism in the inhibitory Fc receptor leads to inadequate control of B cell activation

• Environmental Factors – UV irradiation, Cigarette smoking, Sex hormones, Drugs (procainamide and hydralazine)

• Immunologic abnormalities –

1. Type 1 Interferons – for unknown reasons abnormally large amounts IFN alpha are produced

2. TLR signals – that recognize RNA and DNA, activate B cells specific for nuclear antigens

3. Failure of B cell tolerance – high frequency of auto-reactive B cell production compared to normal individuals

4. CD4 helper T cells, which escape tolerance

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Gram stain testing is a method for classifying bacteria based on their cell wall. It allows scientists to determine whether an organism is gram-positive or gram-negative.

Gram-positive bacteria are bacteria with thick cell walls. In a Gram stain test, these organisms yield a positive result. During the procedure, crystal violet dye is applied to a sample of bacteria. Under a microscope, gram-positive bacteria appear purple-blue because their thick peptidoglycan membrane can hold the dye. This chemical dye can stain thick peptidoglycan layers.

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Cellulitis is an acute inflammatory condition of the dermis and subcutaneous tissue.

Most often caused by Group A B-hemolytic streptococci (Streptococcus pyogens) or Staphylococcus aureus

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Abnormality in formation / distribution of pigmentation in skin either hyperpigmentation / hypopigmentation

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A kidney biopsy is a procedure to remove a small piece of kidney tissue that can be examined under a microscope for signs of damage or disease.

It allowed for better recognition and classification of lupus nephritis (LN).

Lupus nephritis is a type of kidney disease caused by systemic lupus erythematosus (SLE or lupus).

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Refer to 1C

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Desquamated: Shedding of outermost membrane
Erythematosus rash: Redness lesion

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Purulent: containing pus (= thick, yellowish liquid that comes from an infection in the body)
Laceration: A laceration is a wound that occurs when skin, tissue, and/or muscle is torn or cut open. Lacerations may be deep or shallow, long or short, and wide or narrow. Most lacerations are the result of the skin hitting an object, or an object hitting the skin with force.

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Systemic: Whole body system
Lupus: Wolf

Erythema: Redness

Formation of autoantibodies against DNA and other nuclear antigens, resulting in accumulation of antigen-antibody complexes in blood vessels and other organs, where they trigger widespread connective tissue inflammation.

Named for skin lesions once likened to a wolf bite.

Causes fever, fatigue, joint pain, weight loss, intolerance of bright light and a butterfly rash across the nose and cheeks. Death may result from renal failure.

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Gender: Females of all ages are affected far more than men (estimated range from 4-12female: 1 male). Besides, women of childbearing ages (15-44 years) are at the greatest risk of developing SLE.

Ethics:  African Americans, Latinos, Asians & American Indians are affected more than Caucasians

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It is a red or purplish facial rash with a “butterfly” pattern on the face. It may be flat, raised or scaly. It may occur due to rosacea, cellulitis, and dermatomyositis but it is commonly seen in patients with SLE. It may not cause itchy and pain if it occurs because of SLE. UV light can trigger the malar rash. Around 40-70% of people with SLE find that UV light will exacerbate their symptoms.

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SLE:

-Supplements(Vit. A,D, E and fish oil)

-exercise

-consuming a diet high in anti-inflammatory foods (tomatoes, turmeric, tomatoes, berries, fatty fish, and leafy vegetables).

All of the approaches can help to manage symptoms and improve immune function, without raising the risk of complications

Cellulitis:

-cover the affected skin properly will help it heal and prevent irritation

-always keep the wound clean

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-Exposure to environmental factors
-Cell damage
-Innate and adaptive immune systems
(Toll-like receptor--> TLR dependent/ independent)
-NETosis
-T&B lymphocytes

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Sinusitis

Yellow thick / greenish drainage discharge from the nose

Obstruction of the nasal results in difficulty in breathing

Eye, cheeks, nose and forehead pain, swelling and tenderness.

The sense of smell and taste is reduced

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Sinusitis - inflammation of the tissue lining the sinuses. It usually caused by an infection.

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Kidney failure

Strokes

Seizures

Memory changes

Inflammation of the chest cavity lining

Increase the risk of bleeding or blood clotting

Inflammation of the blood vessels

Pericarditis (inflammation of the pericardium)

Heart attack

Behavior changes

Vision problems

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Hormonal factors – Hormone such as estrogen could trigger lupus or make it worse. Some women with lupus also get symptom flare-ups around their period or during pregnancy when the estrogen levels are higher.

Infection - Viruses and bacteria may also cause lupus flares.

Environmental factors - Exposure to ultraviolet light from light bulbs or the sun, exposure to silica dust, which is found in soil, cigarette smoke, pottery, and cleaning powders, exposure to smoking.

Lifestyle – Stress, Exhaustion, Smoking.

Race - highest rates of lupus (SLE) : people of Asian, and African ; the lowest rates : people of European

Age - Most people are diagnosed with lupus between the ages of 15 and 45

Sex - 9 out of 10 people diagnosed with lupus are female.

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No specific drug interactions between prednisolone, mycophenolate mophetil & hydroxychloroquine.

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HYDROXYCHLOROQUINE

Side effects:
-headache
-dizziness
-loss of appetite
-nausea
-diarrhoea
-stomach pain
-vomiting
-rash
-difficulty reading or seeing (words, letters, or parts of objects missing)
-sensitivity to light
-blurred vision
-changes in vision
-seeing light flashes or streaks
-difficulty hearing
-ringing in ears
-muscle weakness
-unusual bleeding or bruising
-bleaching or loss of hair
-mood or mental changes
-irregular heartbeat
-drowsiness
-convulsions
-decreased consciousness or loss of consciousness
-thinking about harming or killing yourself

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MYCOPHENOLATE MOPHETIL

Side effects:
-constipation
-stomach pain or swelling
-nausea
-vomiting
-difficulty falling asleep or staying asleep
-pain, especially in the back, muscles, or joints
-headache
-gas
-prickling, tingling, or burning feeling on the skin
-muscle stiffness or weakness
-diarrhoea, sudden severe stomach pain
-swelling of the hands, arms, feet, ankles, or lower legs
-difficulty breathing
-chest pain
-rash
-itching
-fast heartbeat
-dizziness
-fainting
-lack of energy
-pale skin
-unusual bleeding or bruising
-black and tarry stools
-red blood in stools
-bloody vomit
-vomit that looks like coffee grounds
-blood in urine
-yellowing of the skin or eyes

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PREDNISOLONE

Common side effects of prednisolone, especially with high doses for long periods, include:

fluid retention, which can lead to heart problems

trouble sleeping

bloating of the face and swelling of the abdomen

weight gain

irregular periods

muscle cramps

thin skin with easy bruising and acne

slowed growth in children

osteoporosis (thinning of the bone)

Less common side effects of prednisolone include:

headaches

diarrhoea or constipation

nausea, vomiting or anorexia

cataracts

increased frequency or severity of infections

reduced thyroid function

See your doctor immediately or go to the emergency department of your nearest hospital if you experience any of these serious side effects:

severe stomach or gut pain

epileptic fits

sudden changes in your vision

symptoms such as severe dizziness, fainting, weakness, chest pain or irregular heartbeat

mental disturbances

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Co-amoxiclav

Allopurinol – increase the risk of skin rash

BCG - reduce the anti-tumor activity of BCG in the bladder

methotrexate - increased side effects such as nausea, vomiting, mouth ulcers, and low blood cell counts, which can make you more likely to develop anemia, bleeding problems, and infections.

mycophenolate mofetil - reduce the therapeutic effect of mycophenolate mofetil

sodium picosulfate, a stimulant laxative – reduce the therapeutic effect of sodium picosulfate

tetracyclines – reduce the therapeutic effects of amoxicillin

warfarin – increase the risk of bleeding

Methylprednisolone may reduce the effects of lisinopril in lowering blood pressure.

Lisinopril

Aliskiren, angiotensin-receptor blockers (ARBs) such as valsartan – increase the risk of serious side effect such as kidney problems, hypotension and hyperkalemia

Insulin -  increase the risk of hypoglycemia

Diuretics, such as hydrochlorothiazide - hypotension

Lithium - increase the levels of lithium in your body, which can lead to a lithium overdose.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen - raise your risk for kidney damage.

Celecoxib - decrease the therapeutic effects of Lisinopril, affect the kidney function

Prednisolone – decrease the therapeutic effect of Lisinopril.

Methylprednisolone - decrease the therapeutic effect of Lisinopril.

Celecoxib

Warfarin – increase the risk of bleeding

Anti-platelet drugs such as clopidogrel – increase the risk of gastrointestinal bleeding complication

NSAIDs such as ibuprofen - increased risk of serious gastrointestinal toxicity including inflammation, bleeding, ulceration, and perforation

Lithium – cause lithium toxicity

ACE inhibitors such as Lisinopril – decrease the therapeutic effects of Lisinopril, affect the kidney function

ARB such as valsartan - decrease the therapeutic effects of Lisinopril, affect the kidney function

Prednisolone - increase the risk of side effects in the gastrointestinal tract such as inflammation, bleeding, ulceration, and rarely, perforation

Methylprednisolone - increase the risk of side effects in the gastrointestinal tract such as inflammation, bleeding, ulceration, and rarely, perforation

Atorvastatin

Antibiotics such as erythromycin - increases your risk for muscle problems

Antifungal medication such as Ketoconazole – increase the risk of liver damage and cause breakdown of skeletal muscle tissue

Niacin – increase the risk of liver damage and cause breakdown of skeletal muscle tissue

Rifampin – decrease the therapeutic effect of atorvastatin

Digoxin -  increase the plasma digoxin concentration

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Clinical Practice Guidelines on Management of Hypertension (5th Edition)

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Blood pressure
Blood pressure is the force of blood pushing against the walls of arteries as the heart pumps blood. Normal blood pressure for adults is defined as a systolic pressure of less than 120 and a diastolic pressure of less than 80.
Based on the case, the patient develops Stage 2 Hypertension.

Heart rate or pulse is the number of time the heart beats per minute. Pulse rates vary from person to person. A normal heart rate for a healthy adult at rest from 60 to 80 beats per minute. A faster than average pulse can indicate such health problems as infection, dehydration, stress, anxiety, a thyroid disorder, shock, anemia or certain heart conditions.
Based on the case, the heart rate is high.

Respiratory rate is the number of breaths an individual takes in one minute. The normal respiratory rate for healthy adults at rest is between 12 and 20 breaths per minute. A respiration rate under 12 and above 20 is considered abnormal.
Based on the case, the patient develops a high respiration rate.

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There are 2 types of kidney biopsy: percutaneous kidney biopsy and Laparoscopic kidney biopsy

The most common type of biopsy is a percutaneous kidney biopsy. A doctor inserts a thin needle through the skin into the kidney to obtain samples of the kidney tissue for analysis. The doctor use imaging techniques, such as ultrasound to guide the biopsy needle into the kidney.
Laparoscopic biopsy also called open biopsy. During a laparoscopic biopsy, a doctor collect the tissue sample from the kidney during surgery.

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Malar rash may occur in several diseases and conditions such as SLE, cellulitis, pellagra (systemic disease caused by vitamin B3 niacin deficiency), rosacea (chronic inflammatory skin condition that mainly affects the face) and etc. Sunlight also triggers malar rash.

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SLE is more common in women than men. Women are at ten times more risk of developing SLE compare to men. It appears most often in young women between the ages of 15 and 44.

SLE flare is defined as the symptoms of SLE become worsen.

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kidney test
1.      Serum creatinine

-Creatinine. Creatinine is a waste product from the normal breakdown of muscles in your body

Your kidneys remove creatinine from your blood. Health care professionals use the amount of creatinine in your blood to estimate your glomerular filtration rate (GFR). As kidney disease gets worse, the level of creatinine goes up.

2.      BUN

-The BUN test measures the amount of urea nitrogen in your blood.

-Urea nitrogen is a waste product that your kidneys remove from your blood.

- Higher than normal BUN levels may be a sign that your kidneys aren't working well.

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A kidney biopsy can

confirm a diagnosis of lupus nephritis

find out how far the disease has progressed

guide treatment

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CRP test:
-synthesized by liver

-level rises in response to inflammation

- has both proinflammatory and anti-inflammatory properties. It plays a role in the recognition and clearance of foreign pathogens and damaged cells

-when it’s activated by autoantibodies, worsen tissue damage in certain cases by activation of the complement system and thus inflammatory cytokines

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Complete blood count
-provides information about the red blood cell (RBC), white blood cell (WBC), platelet counts, and health of RBCs, all of which may be abnormal in lupus and may need treatment. Common issues are:
1. Anemia
-Autoimmune Hemolytic Anemia (AIHA)
-breakdown of RBCs due to auto-antibodies
- may manifest in SLE patients
2.Leukopenia
-. Almost all untreated patients with lupus have leukopenia
− it can be a clue to the diagnosis.
-White blood cell counts can be low (leukopenia) due to lupus, immunosuppressive therapy, or the presence of a virus.
-However, High WBC counts may signal infection but also occur when individuals are on corticosteroids such as prednisone.
-It can be concluded that even small doses of prednisone, administered over a prolonged period of time, can induce extreme and persistent leukocytosis
3.Thrombocytopenia
-common in lupus and can be caused by the disease, medication toxicity, and other illnesses.
-attributed to an autoimmune mechanism similar to that of idiopathic immune thrombocytopenia.

-all of these occur because lupus is an autoimmune disease. In autoimmune diseases, the immune system mistakenly attacks healthy cells.

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ANA test
- antinuclear antibody is the autoantibodies produced by the immune system that attack the body’s own cells, and are a hallmark of lupus.
-usually measured as 0 to 4+ or as a titer (the number of times a blood sample can be diluted and still be positive). ANA of 0, 1+ or 2+, or at titers less than 1:80 (diluted 80 times) usually do not indicate a significant problem. ANA titers at higher levels more likely indicate the presence of autoimmune disease.
-ANA is a screening test, since almost all patients with lupus have a strongly positive test. However, a positive ANA test result does not by itself confirm a diagnosis for lupus. About 10% of people who do not have an autoimmune disease, as well as many who have other autoimmune diseases (such as thyroid disease) also have positive ANA tests, but usually less strongly positive. Once a person has a positive result, their ANA generally remains positive, so future ANA tests need not be repeated.

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MONITOR: Corticosteroids may antagonize the effects of antihypertensive medications by inducing sodium and fluid retention.

MANAGEMENT: Patients on prolonged (i.e., longer than about a week) or high-dose corticosteroid therapy should have blood pressure, electrolyte levels, and body weight monitored regularly, and be observed for the development of edema and congestive heart failure. The dosages of antihypertensive medications may require adjustment.

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Same as the drug interactions of prednisolone and lisinopril

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MONITOR: Nonsteroidal anti-inflammatory drugs (NSAIDs) may attenuate the antihypertensive effects of ACE inhibitors. NSAID will induced inhibition of renal prostaglandin synthesis, which results in unopposed pressor activity producing hypertension. In addition, NSAIDs can cause fluid retention, which also affects blood pressure.

MONITOR: Concomitant use of NSAIDs and ACE inhibitors may cause deterioration in renal function, especially in patients who are elderly or volume-depleted. Acute renal failure may occur, although effects are usually reversible. Chronic use of NSAIDs alone may be associated with renal toxicities, including elevations in serum creatinine and BUN, tubular necrosis, glomerulitis, renal papillary necrosis, acute interstitial nephritis, nephrotic syndrome, and renal failure. ACE inhibitors can further worsen renal function by decreasing glomerular filtration.

MANAGEMENT: Patients receiving ACE inhibitors who require prolonged (greater than 1 week) concomitant therapy with an NSAID should have blood pressure monitored more closely following initiation, discontinuation, or change of dosage of the NSAID. Renal function should also be evaluated periodically during prolonged coadministration.

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MONITOR: The combined use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the potential for serious gastrointestinal (GI) toxicity, including inflammation, bleeding, ulceration, and perforation. In a large, case-control study of elderly patients, those who used corticosteroids and NSAIDs concurrently had an estimated relative risk (RR) for peptic ulcer disease and GI hemorrhage of 14.6 compared to those who used neither. Corticosteroid use was associated with a doubling of the risk (estimated RR = 2.0), but the risk was confined to those who also used NSAIDs. It is possible that both categories of agents are ulcerogenic and have additive effects on the GI mucosa during coadministration.

MANAGEMENT: Caution is advised if corticosteroids and NSAIDs are used together, especially in patients with a prior history of peptic ulcer disease or GI bleeding and in elderly and debilitated patients. During concomitant therapy, patients should be advised to take the medications with food and to immediately report signs and symptoms of GI ulceration and bleeding such as severe abdominal pain, dizziness, lightheadedness, and the appearance of black, tarry stools. The selective use of prophylactic anti-ulcer therapy (e.g., antacids, H2-antagonists) may be considered.

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Same as the drug interactions of prednisolone and celecoxib

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MONITOR: Theoretically, drugs that alter the gastrointestinal flora (e.g., antibiotics) may reduce the oral bioavailability of mycophenolic acid products. Some investigators believe that antimicrobials may interfere with the enterohepatic recirculation of mycophenolic acid by decreasing bacterial hydrolytic enzymes in the gastrointestinal tract that are responsible for regenerating mycophenolic acid from its glucuronide metabolite following first-pass metabolism.

MANAGEMENT: Close clinical and laboratory monitoring for evidence of diminished immunosuppressive effect of mycophenolic acid is recommended during concomitant therapy with anti-infective agents.

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Organ damage
Oral ulcers
Arthritis
Osteoporosis
Raynaud's phenomenon
seizures, psychosis
lung, heart, kidney problems
blood cell and immunological abnormalities.

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Lupus is an autoimmune disease that can weaken the immune system (more prone to get infection)
- Makes the patient vulnerable to cellulitis and other infections, such as colds, and the flu.

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A kidney biopsy can help healthcare professionals

- check for signs of kidney inflammation, scarring, infection, or unusual deposits of a protein called immunoglobulin

- identify which parts of your kidney are damaged and how likely it is the damage will get worse

- determine the best way to treat your kidney problem

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Break in skin barrier- entry of pathogen- organism virulence overwhelms host defense mechanism (neutrophils, eosinophils, basophils, and mast cells)-  localize inflammation and cellular debris accumulates - cellulitis - the organism invades tissue around the initial wound.

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- educate the patients to maintain healthy lifestyles and correct ways to avoid SLE and cellulitis worsen
- ensure the patients take the medications follow the prescriptions

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Nonpharmacological treatment for SLE
- eat healthy
- avoid weight gain
- exercise
- control BP and cholesterol

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1.      avoiding over-exposure to sunlight with the use of adequate sunscreen protection

2.      avoiding "live" vaccination if on immunosuppressive agents

3.      adherence to a diet low in saturated fat and high in fish oil

4.      stress avoidance

5.      smoking cessation.

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Non-pharmacological treatment for Cellulitis

- diabetes or poor circulation patients should observe their legs every day
- Avoid injury by wearing proper shoes
- Avoid wound

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Normal value
BP: 120/80 mmHg
HR: 60-100 beats per min
RR: 16-20 breaths per min

Case
Blood pressure higher
Normal heart rate (almost higher than normal rate)
Respiratory rate higher

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UV light - cell apoptosis- nuclear antigen- immune cell attack- B cells produce antibodies (antinuclear antibodies) - antigen-antibody complex formed - deposit and stick on vessel wall - local inflammatory - cell membrane with openings - fluid and molecules flows inside - cells burst and die

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Stages of Cellulitis:
Stage I -  No systemic toxicity and no comorbidities
Stage II - Systemic toxicity and comorbidities
Stage III - Significant systemic toxicity and comorbidities
Stage IV - Sepsis and life-threantening

Medication used
- intravenous injection antibodies for Stages 3 and 4.
- Flucloxacillin (1st choice)
- Clarithromycin (alternative for flucloxacillin allergy)
- Clindamycin
- Co-amoxiclav (no for penicillin allergy)

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1.  Family history
2.  Sex, age, race
3.  Being around smoke, too much sunlight, or chemicals
4.  Medication that increases the risk of SLE (autoimmune disorder)
- Procainamide, Hydralazine, Isoniazid

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Hydroxychloroquine
- antimalarial medication used to treat uncomplicated cases of malaria
- treatment of rheumatoid arthritis and lupus erythematosus.

MOA:
- Alter the pH of the lysozomes, reduces low-affinity self-antigen presentation in immune diseases, and interfere with the ability of plasmodia to proteolyze hemoglobin for their energy requirements.
- Hydroxychloroquine inhibits antigen processing and MHC dimerization, inhibits antigen presentation of the cell, and reduces the inflammatory response.
- Elevated pH in the vesicles may alter the recycling of MHC complexes so that only the high-affinity complexes are presented on the cell surface.
- Self-peptides bind to MHC complexes with low affinity, so they will be less likely to be presented to autoimmune T cells.
- Hydroxychloroquine also reduces the release of cytokines like interleukin-1 and tumor necrosis factor, possibly through inhibition of Toll-like receptors.

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Mycophenolate Mophetil
- Reversible IMP dehydrogenase inhibitor
- prevent organ rejection during transplantation (combine with cyclosporine and corticosteroid)
- treat nephritis and autoimmune diseases (does not cause nephrotoxicity or fibrosis)
- second-line treatment for autoimmune hepatitis, lupus-associated nephritis, and dermatitis

MOA:
- Mycophenolic acid (MPA) prevents Lymphocyte and monocyte adhesion to endothelial cells of blood vessels via the glycosylation of cell adhesion molecules.
- Mycophenolate mofetil (MMF) interferes with the synthesis of DNA, RNA, and protein required for immune cell production
- MMF depletes tetrahydrobiopterin, the function of nitric oxide synthase enzyme decreases, and the production of peroxynitrite (promotes inflammation) decreases.

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Prednisolone
- Man-made corticosteroid hormone
- Anti-inflammatory, immunosuppressive agent,  anti-neoplastic, vasoconstriction
- Treat endocrine, rheumatic, and hematologic disorders
- Treat dermatologic disorders, ophthalmic, respiratory, and GI diseases.
- Treat allergic and edematous states
- Risk of the severity of adverse effects can be increased when used with Mycophenolate mofetil and hydroxychloroquine.

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Cellulitis: a common, potentially serious bacterial skin infection. The affected skin is swollen and inflamed and is typically painful and warm to the touch. It usually affects the lower legs, but it can occur on the face, arms and other areas. The infection happens when a break in the skin allows bacteria to enter. When it is left untreated, the infection can spread to the lymph nodes and bloodstream and rapidly become life-threatening.

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General symptoms: Fever, weight lose
Specific symptoms: depend on the organ and tissues affected

Medication used
1. Antimalarial drugs (1st choice): hydroxychloroquine
2. Immunosuppresants (severe case): Azathioprine
-Calcineurin inhibitor: voclosporin, tacrolimus
3. Corticosteroids (used with cautions): prednisone
4. NSAIDs (used with cautions): ibuprofen
5. Biologics (rare used): Belimumab, Rituximab

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Purulent: consisting of pus (a thick yellowish or greenish opaque liquid produced in infected tissue, consisting of dead white blood cells and bacteria with tissue debris and serum.)

Laceration: a wound that is produced by the tearing of soft body tissue. A laceration wound is often contaminated with bacteria and debris from whatever object caused the cut.

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A complex interaction of impaired apoptotic clearance, upregulation of innate and adaptive immune system, complement activation, immune complexes, and tissue inflammation culminates in a self-sustained autoimmune process

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- Difficult to diagnose
- Diagnosed only when the patients meet 4 out of 11 criteria.
- 11 criteria from skin, mucosa, serosa, joints, kidneys, brain, blood, and antibodies.

Laboratory test
- Full blood count, electrolyte urea creatine, urinalysis, urine microscopy, urine albumin creatinine ratio
- ANA test (for suspected case)
- ENA test

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- Any abnormality in the formation or distribution of pigment in the skin.
- hyperpigmentation OR hypopigmentation

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- To diagnose kidney problem
- Remove a small piece of kidney tissue and examined it under a microscope.

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- Serious bacterial skin and soft tissue infection.
- usually no spread from person to person.

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- Malar rash

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- Shedding of the outer skin layer.

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- Red facial rash with a “butterfly” pattern.
- Covers the cheeks and the bridge of the nose.

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- A thick and milky fluid comes out from a wound.
- A sign of infection.

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- An autoimmune disease
- The immune system attacks its cells or tissues, leading to inflammation and tissue damage in the affected organs. (joints, skin, brain, lungs, kidneys, blood vessels)

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- Pharmacists should monitor medication tolerance and other health conditions, such as high blood pressure and diabetes

- Pharmacist should educate the patient regarding lupus

- Pharmacist should provide counselling on the best ways to take medications and what to expect when starting or stopping them

- Pharmacists can also seek advice or help from a rheumatologist (for SLE) and a dermatologist (for skin lupus) to prescribe the most effective treatment and for consultation when medications are not working

- Dermatologist: A doctor who specializes in conditions involving the skin, hair, and nails

- Rheumatologist: A pediatrician who is trained in the diagnosis, and treatment of diseases that affect the muscles, bones, joints, ligaments and tendons