lupus profundus

systemic lupus erythematosus, abbreviatedas sle. this is a systemic disease, which means thatit can affect the whole body systemically. the brain, skin, heart, lungs, kidneys, joints,the immune system, the vascular system, and the list goes on. lupus means wolf. erythematosus means reddening of the skin. why did i show a red butterfly? because a very typical sign of sle is a butterflyshaped reddening of the skin. the way i remember this disease, is to imaginea wolf that attacks a woman, and why a woman?

because 9 out 10 patients are women. so the wolf bites the face of the woman causinga butterfly shaped erythema on her face. then the wolf continues to bite all her organsone by one, because this disease is a systemic disease, which means that it can affect allthe organs systemically. of course this disease has nothing to do witha wolf. but sle is an autoimmune disease, which meansthat this woman called emma have an immune system that attacks her own body, insteadof only attacking bacterias, viruses and parasites. so emma have an immune system that acts asa wolf inside her.

i will show you how we can find out if emmareally has sle by diagnosing her. and then we will look at what type of medicationswe can give her. i want you to remember at least one thingfrom this presentation. that is systemic lupus international collaboratingclinics, abbreviated as slicc. slicc is a criterion that can help in thediagnosis of sle. slicc contains clinical criteria, immunologiccriteria and biopsy criteria. we need more than 4 criteria with at least1 clinical and 1 immunologic. or we need 1 biopsy criteria and 1 immunologiccriteria.

so what does these 3 words mean? clinical, immunologic and biopsy? the synonym for clinic, is hospital. so clinical criteria stand for the symptoms,signs and lab values of a patient in the hospital. immunology deals with the immune system thatprotects you from bacterias, viruses, and immunologic criteria are usually lab teststhat detect any problem with the immune system. biopsy means that a doctor cuts out a pieceof an organ. for example, a small piece of kidney can becut out, and then the doctor puts this piece of kidney in a microscope and looks for diseases.

clinical criteria can be divided into alopecia,which means hairloss. skin problemsulcers heart diseaseslung diseases kidney problemsjoint pain problems with the nervous systemand blood diseases. skin problems can be grouped under the namecutaneous lupus erythematosus. we can divide these skin diseases into acutesubacute and chronic, based on the timing of the diseases. acute diseases are usually those that happensuddenly with a short duration.

chronic diseases are ongoing for a long time. whereas subacute means those diseases thatare not yet chronic but has passed the acute phase. a way to remember these timing are to memorize2 numbers. 1 and 3. why? because the duration of acute diseases areusually less than 1 month, subacute are 1 to 3 months, and chronic are more than 3 monthsin duration. so which are the acute type of skin problems?

butterfly erythema, which is a reddening ofthe face in a butterfly shape. it usually affects the cheeks or also calledmalar region, and therefore it is sometimes called malar erythema. it does not affect the nasolabial region. there can also be bullous lesions which areblisters that can be a mix of small grouped vesicles to large tense bullae. bullae are elevating the skin and are filledwith fluid. toxic epidermal necrolysis-like sle, is adetachment of the epidermis, the upperlayer of the skin, resulting in exfoliation, meaningthat the upperlayer just falls off.

this is very dangerous, because the skin isthe organ that protects against infections. so if you loose a large part of your skin,then sepsis can happen, which means that bacterias easily invade your vascular system, sincethere is no skin to protect you. this can lead to something called septic shock,which can lead to death. maculopapular rash is another acute sign. macules are flat spots up to 1 cm, and papulesare bumps up to 1 cm. maculopapular is a combination between maculesand papules. photosensitivity can also be seen which meansthat the skin is much more sensitive to sunlight than normally.

this can cause cause solar urticaria, whichis a vascular reaction of the skin that cause pathches. patches are flat lesions like macules, butthey are bigger than 1 cm. so one difference between macules and patchesis the size. macules are less than 1 cm, whereas patchesare more than 1 cm. so the acute cutaneous lupus erythematosuscan be divided into 5 lesions: butterfly shaped erythema, bullous lesions, toxic epidermalnecrolysis, maculopapular rashes, and photosensitive solar urticarias. subacute cutaneous lupus erythematosus canbe divided into 2 types.

one is annular polycyclic lesions. the word polycyclic refers to more than 1ring structures that can be seen in chemistry for example. the word annular also refers to a ring-shapedstructure. so annular polycyclic lesions are ring-shapedskin lesions that usually occur on sun-exposed areas of the skin. nonindurated psoriaform is the other typeof subacute skin lesions. psoriaform means that it looks like psoriasis. nonindurated means that it is not hardas psoriasis.

subacute can be divided into annular polycyclicand nonindurated psoriaform lesions chronic skin lesions are chilblain lupus,that affects toes, fingers, nose, and ears during cold weather. these are painful, bright red nodules. nodules means a swelling of the skin thatis up to 1 cm diameter. discoid rash can also be seen. discoid refers to the disc shape of theselesions. we can divide discoid into classical type. discoid lesions can be divided into localized,which means that discoid lesions appear above

the neck,and generalized, which means that discoid lesions can appear both above and below theneck. lichen planus is an inflammatory disease thatcan affect the skin and oral mucosa. here we see a picture of whitish lichen planuson the oral mucosa. the word lichen means tree-moss as you cansee here on the picture. so this disease is looking like a tree mossbut with a whitish color. in sle patients this happen, that a discoidlesion is seen together with lichen planus. verrucous lesions or also called hypertrophiclesions are skin that hypertrophies, which means that the skin cells increase in numberand cause these hard wartlike lesions, especially

on extensor arms. mucosal lesions can affect the mucosal membranearound the teeth, the tongue, and hardpalate panniculitis or also called profundus, isan inflammation and destruction of the subcutaneous fat. tumidus lesions are pinkish urticarial non-scarringplaques usually in sun-exposed areas. plaques are elevation of the skin similarto papule, but they differ in size. so plaques are more than 1 cm in diameter,whereas papules are less than 1 cm. the chronic skin lesion are chilblain, discoid,discoid with lichen planus, hypertrophic, mucosal, panniculitis, and tumidus.

ulcers can appear on the mucosal membrane,on for example the hardpalate, buccal region, on the tongue, and on the nasal septum. inflammation can affect the heart causingpericarditis. here we see a normal normal heart on the upperpicture, and a reddish heart on the lower picture. inflammation is causing redness, pain, heat,swelling and loss of function. the heart wall rub against each other causinga typical pericardial rub sound that one can hear with a stethoscope. here we see a man having a painful pericarditispericardial effusion can also happen, which

means that fluid accumulates around the heartcausing a typical waterbottle-shaped heart on x-ray. as i mentioned, pericardial rub sounds canbe heard with a stethoscope. inflammation can also affect the lungs. so similar to the heart, there will be inflammation,pain, pleural friction rub sounds, and pleural effusionhere we can see the pleural effusion that have accumulated between the 2 layers of thelungs. this is how pleural friction rub sounds like. imagine walking on snow when you hear thissound.

we need to collect urine to find kidney problems. more than 500 mg of protein in the urine duringa 24 hour period can be seen in sle patients. this is called proteinuria, meaning proteinin the urine, which is not normal. we can also find red blood cell casts in theurine by analyzing the urine in a microscope. these casts are formed by red blood cellsthat stick together. blood in the urine is not normal. it suggest that something is wrong with thekidney. synovitis is inflammation of the synovialmembrane of the joints. polyarthritis can be seen in sle.

poly stands for that more than 1 joint isaffected. arthritis is inflammation of joint. so more than 1 joint will be inflamed causingpain. the nervous system can also be affected bysle. seizures can happen, which are hyperexcitationof neurons in the brain, sometimes leading to muscle contractions. psychosis and acute confusional state, alsocalled delirium can happen. psychosis and delirium patients usually sufferfrom hallucinations. neuropathies can be seen in sle.

neuropathy means neurons that are diseased. the neurons can be in the cranial part, peripheralpart, in the spinal cord which is then called myelitis, or single nerves can be damagedwhich is then called mononeuropathy, mono standing for single. or multiple single nerves in different areasof the body can be damaged, which is then called multiple mononeuropathy. what can we see in the blood? with a microscope we can distinguish differentblood cells. here is a picture showing the blood cells.

the blood cells originate from one cell calledmultipotential hematopoetic stem cell. this cell can produce myeloid cells, and lymphoidcells. the myeloid cells can produce erythrocytes,also called red blood cells. but in sle hemolytic anemia can be seen, whichmeans that the erythrocytes can damaged and therefore anemia will happen, which meansthat not enough oxygen is transported to the tissues. the myeloid cells can also produce megakaryocytes,that can further produce thrombocytes, also called platelets. but in sle the number of thrombocytes canbe reduced, and we call this thrombocytopenia.

penia stands for less of something, inthis case we have a penia of thrombocytes, so thrombocytopenia. the symptom of thrombocytopenia is usuallypetechiae which are small purplish spots on the skin. leukopenia can happen in sle which is a reducednumber of leukocytes, which are white blood cells, with neutrophils being the most commonwhite blood cell. lymphopenia can also be seen, which are reducednumber of lymphocytes. so the clinical criteria were alopecia, skinlesions, ulcers, diseases of the heart, lungs, kidneys, joints, nervous system and the blood.

the immunologic criteria are related to autoantibodies,meaning that the antibodies of the immune system attacks itself, instead of only attackingbacterias etc. here we have a cell, with its nucleus, containingchromosomes that contain dna. in sle, the antibodies attack your own nuclearproteins, for example your own dna, or rna binding proteins called smith proteins. so in sle we check for antinuclear antibodylevels, abbreviated as ana. we also check anti-smith and anti-double strandeddna. another immunologic criteria is direct coombstest. here we mix the patients blood together witha coombs reagent, and if red blood cells agglutinate,

meaning they stick together, then we havea positive test result. the complement system helps or complementsthe antibodies to fight infections. in sle we can see a low number of these complementproteins. the complement proteins are numbered c1 toc9, and it is the c3 and c4 complement proteins that are low in sle. ch50 stands for the total complement activity,which is also low in sle. an increased number of antiphospholipid antibodiescan be measured in sle. these antibodies bind to proteins like beta2 glycoprotein 1 on the phospholipid cell membrane.

the function of the beta 2 glycoprotein 1is to prevent phospholipid membrane to activate the thrombosis cascade. we know that thrombosis can cause death. so therefore it is very important to checkthe antiphospolipid antibody level. it is especially important in pregnant women,because these antibodies can cause spontaneous abortion and late fetal death. except antiphospholipid antibodies, sle flarescan also cause fetal death. sle fluctuate between flares and remissions. a flare is a very active disease with manysymptoms, whereas a remission is an inactive

state with few symptoms. during pregnancy, the mother should be monitoredfor any sle flares since these can lead to fetal death. so if a woman wants a child, then pregnancyshould be timed for when sle is in remission for at least 6 months. furthermore, anti-ro antibodies should bemeasured, because if anti-ro is detected, then doctors should warn mothers that thereare risks of the fetus getting a neonatal lupus or even a severe congenital heart blockwhich means the death of the fetus. so it is very important to monitor the fetalheart in this case, with for example an echocardiograph

and a 24-hour holter monitor. lets turn now to the biopsy criteria. here we need a biopsy of the kidney, whichwill show that there is inflammation, called nephritis. but it is not enough with a biopsy, we needan immunologic criteria as well, for example antinuclear antibodies, or anti-double-strandeddna. now lets see how we can treat sle patients. the first thing that we have to do is to removeany type of medication that can cause sle-like symptoms.

these are for example hydralazine, procainamide,and isoniazid. non-steroidal anti-inflammatory drugs arevery useful in sle patients, especially in controling arthralgias, which means painfuljoints. here we can use naproxen, ibuprofen, and diclofenac. antimalarial medications also help jointsproblems, but also skin problems, and they reduces the sle flares. the typical sle medication is hydroxychloroquine,but there are alternative like chloroquine and quinacrine. hydroxychloroquine can in rare cases causeretinal problems, skeletal muscle problems

and cardiac problems. so it is important that the eyes are examinedyearly. corticosteroids are usually the first linetreatment in acute severe sle. we typically begin by giving intravenous methylprednisolonefor 3 days and then we maintain the therapy with prednisone. disease-modifying antirheumatic drugs arealso very important. we can use azathioprine, methotrexate, mycophenolatemofetil, cyclophosphamide together with mesna, and in very severe cases intravenous immunoglobulin. it is well known that corticosteroid use fora long time can cause osteoporosis, which

means bone weakening. therefore it is important to consider givingcalcium, vitamin d, and bisphosphonate. so to conclude, we can say that emma has sle,which is a systemic autoimmune disease, that affects her whole body systemically. the brain, skin, heart, lungs, kidneys, joints,the immune system, and the vascular system. the typical butterfly-shaped erythema canbe seen in sle patients. thank you very much for listening!

lupus panniculitis

systemic lupus erythematosus, abbreviatedas sle. this is a systemic disease, which means thatit can affect the whole body systemically. the brain, skin, heart, lungs, kidneys, joints,the immune system, the vascular system, and the list goes on. lupus means wolf. erythematosus means reddening of the skin. why did i show a red butterfly? because a very typical sign of sle is a butterflyshaped reddening of the skin. the way i remember this disease, is to imaginea wolf that attacks a woman, and why a woman?

because 9 out 10 patients are women. so the wolf bites the face of the woman causinga butterfly shaped erythema on her face. then the wolf continues to bite all her organsone by one, because this disease is a systemic disease, which means that it can affect allthe organs systemically. of course this disease has nothing to do witha wolf. but sle is an autoimmune disease, which meansthat this woman called emma have an immune system that attacks her own body, insteadof only attacking bacterias, viruses and parasites. so emma have an immune system that acts asa wolf inside her.

i will show you how we can find out if emmareally has sle by diagnosing her. and then we will look at what type of medicationswe can give her. i want you to remember at least one thingfrom this presentation. that is systemic lupus international collaboratingclinics, abbreviated as slicc. slicc is a criterion that can help in thediagnosis of sle. slicc contains clinical criteria, immunologiccriteria and biopsy criteria. we need more than 4 criteria with at least1 clinical and 1 immunologic. or we need 1 biopsy criteria and 1 immunologiccriteria.

so what does these 3 words mean? clinical, immunologic and biopsy? the synonym for clinic, is hospital. so clinical criteria stand for the symptoms,signs and lab values of a patient in the hospital. immunology deals with the immune system thatprotects you from bacterias, viruses, and immunologic criteria are usually lab teststhat detect any problem with the immune system. biopsy means that a doctor cuts out a pieceof an organ. for example, a small piece of kidney can becut out, and then the doctor puts this piece of kidney in a microscope and looks for diseases.

clinical criteria can be divided into alopecia,which means hairloss. skin problemsulcers heart diseaseslung diseases kidney problemsjoint pain problems with the nervous systemand blood diseases. skin problems can be grouped under the namecutaneous lupus erythematosus. we can divide these skin diseases into acutesubacute and chronic, based on the timing of the diseases. acute diseases are usually those that happensuddenly with a short duration.

chronic diseases are ongoing for a long time. whereas subacute means those diseases thatare not yet chronic but has passed the acute phase. a way to remember these timing are to memorize2 numbers. 1 and 3. why? because the duration of acute diseases areusually less than 1 month, subacute are 1 to 3 months, and chronic are more than 3 monthsin duration. so which are the acute type of skin problems?

butterfly erythema, which is a reddening ofthe face in a butterfly shape. it usually affects the cheeks or also calledmalar region, and therefore it is sometimes called malar erythema. it does not affect the nasolabial region. there can also be bullous lesions which areblisters that can be a mix of small grouped vesicles to large tense bullae. bullae are elevating the skin and are filledwith fluid. toxic epidermal necrolysis-like sle, is adetachment of the epidermis, the upperlayer of the skin, resulting in exfoliation, meaningthat the upperlayer just falls off.

this is very dangerous, because the skin isthe organ that protects against infections. so if you loose a large part of your skin,then sepsis can happen, which means that bacterias easily invade your vascular system, sincethere is no skin to protect you. this can lead to something called septic shock,which can lead to death. maculopapular rash is another acute sign. macules are flat spots up to 1 cm, and papulesare bumps up to 1 cm. maculopapular is a combination between maculesand papules. photosensitivity can also be seen which meansthat the skin is much more sensitive to sunlight than normally.

this can cause cause solar urticaria, whichis a vascular reaction of the skin that cause pathches. patches are flat lesions like macules, butthey are bigger than 1 cm. so one difference between macules and patchesis the size. macules are less than 1 cm, whereas patchesare more than 1 cm. so the acute cutaneous lupus erythematosuscan be divided into 5 lesions: butterfly shaped erythema, bullous lesions, toxic epidermalnecrolysis, maculopapular rashes, and photosensitive solar urticarias. subacute cutaneous lupus erythematosus canbe divided into 2 types.

one is annular polycyclic lesions. the word polycyclic refers to more than 1ring structures that can be seen in chemistry for example. the word annular also refers to a ring-shapedstructure. so annular polycyclic lesions are ring-shapedskin lesions that usually occur on sun-exposed areas of the skin. nonindurated psoriaform is the other typeof subacute skin lesions. psoriaform means that it looks like psoriasis. nonindurated means that it is not hardas psoriasis.

subacute can be divided into annular polycyclicand nonindurated psoriaform lesions chronic skin lesions are chilblain lupus,that affects toes, fingers, nose, and ears during cold weather. these are painful, bright red nodules. nodules means a swelling of the skin thatis up to 1 cm diameter. discoid rash can also be seen. discoid refers to the disc shape of theselesions. we can divide discoid into classical type. discoid lesions can be divided into localized,which means that discoid lesions appear above

the neck,and generalized, which means that discoid lesions can appear both above and below theneck. lichen planus is an inflammatory disease thatcan affect the skin and oral mucosa. here we see a picture of whitish lichen planuson the oral mucosa. the word lichen means tree-moss as you cansee here on the picture. so this disease is looking like a tree mossbut with a whitish color. in sle patients this happen, that a discoidlesion is seen together with lichen planus. verrucous lesions or also called hypertrophiclesions are skin that hypertrophies, which means that the skin cells increase in numberand cause these hard wartlike lesions, especially

on extensor arms. mucosal lesions can affect the mucosal membranearound the teeth, the tongue, and hardpalate panniculitis or also called profundus, isan inflammation and destruction of the subcutaneous fat. tumidus lesions are pinkish urticarial non-scarringplaques usually in sun-exposed areas. plaques are elevation of the skin similarto papule, but they differ in size. so plaques are more than 1 cm in diameter,whereas papules are less than 1 cm. the chronic skin lesion are chilblain, discoid,discoid with lichen planus, hypertrophic, mucosal, panniculitis, and tumidus.

ulcers can appear on the mucosal membrane,on for example the hardpalate, buccal region, on the tongue, and on the nasal septum. inflammation can affect the heart causingpericarditis. here we see a normal normal heart on the upperpicture, and a reddish heart on the lower picture. inflammation is causing redness, pain, heat,swelling and loss of function. the heart wall rub against each other causinga typical pericardial rub sound that one can hear with a stethoscope. here we see a man having a painful pericarditispericardial effusion can also happen, which

means that fluid accumulates around the heartcausing a typical waterbottle-shaped heart on x-ray. as i mentioned, pericardial rub sounds canbe heard with a stethoscope. inflammation can also affect the lungs. so similar to the heart, there will be inflammation,pain, pleural friction rub sounds, and pleural effusionhere we can see the pleural effusion that have accumulated between the 2 layers of thelungs. this is how pleural friction rub sounds like. imagine walking on snow when you hear thissound.

we need to collect urine to find kidney problems. more than 500 mg of protein in the urine duringa 24 hour period can be seen in sle patients. this is called proteinuria, meaning proteinin the urine, which is not normal. we can also find red blood cell casts in theurine by analyzing the urine in a microscope. these casts are formed by red blood cellsthat stick together. blood in the urine is not normal. it suggest that something is wrong with thekidney. synovitis is inflammation of the synovialmembrane of the joints. polyarthritis can be seen in sle.

poly stands for that more than 1 joint isaffected. arthritis is inflammation of joint. so more than 1 joint will be inflamed causingpain. the nervous system can also be affected bysle. seizures can happen, which are hyperexcitationof neurons in the brain, sometimes leading to muscle contractions. psychosis and acute confusional state, alsocalled delirium can happen. psychosis and delirium patients usually sufferfrom hallucinations. neuropathies can be seen in sle.

neuropathy means neurons that are diseased. the neurons can be in the cranial part, peripheralpart, in the spinal cord which is then called myelitis, or single nerves can be damagedwhich is then called mononeuropathy, mono standing for single. or multiple single nerves in different areasof the body can be damaged, which is then called multiple mononeuropathy. what can we see in the blood? with a microscope we can distinguish differentblood cells. here is a picture showing the blood cells.

the blood cells originate from one cell calledmultipotential hematopoetic stem cell. this cell can produce myeloid cells, and lymphoidcells. the myeloid cells can produce erythrocytes,also called red blood cells. but in sle hemolytic anemia can be seen, whichmeans that the erythrocytes can damaged and therefore anemia will happen, which meansthat not enough oxygen is transported to the tissues. the myeloid cells can also produce megakaryocytes,that can further produce thrombocytes, also called platelets. but in sle the number of thrombocytes canbe reduced, and we call this thrombocytopenia.

penia stands for less of something, inthis case we have a penia of thrombocytes, so thrombocytopenia. the symptom of thrombocytopenia is usuallypetechiae which are small purplish spots on the skin. leukopenia can happen in sle which is a reducednumber of leukocytes, which are white blood cells, with neutrophils being the most commonwhite blood cell. lymphopenia can also be seen, which are reducednumber of lymphocytes. so the clinical criteria were alopecia, skinlesions, ulcers, diseases of the heart, lungs, kidneys, joints, nervous system and the blood.

the immunologic criteria are related to autoantibodies,meaning that the antibodies of the immune system attacks itself, instead of only attackingbacterias etc. here we have a cell, with its nucleus, containingchromosomes that contain dna. in sle, the antibodies attack your own nuclearproteins, for example your own dna, or rna binding proteins called smith proteins. so in sle we check for antinuclear antibodylevels, abbreviated as ana. we also check anti-smith and anti-double strandeddna. another immunologic criteria is direct coombstest. here we mix the patients blood together witha coombs reagent, and if red blood cells agglutinate,

meaning they stick together, then we havea positive test result. the complement system helps or complementsthe antibodies to fight infections. in sle we can see a low number of these complementproteins. the complement proteins are numbered c1 toc9, and it is the c3 and c4 complement proteins that are low in sle. ch50 stands for the total complement activity,which is also low in sle. an increased number of antiphospholipid antibodiescan be measured in sle. these antibodies bind to proteins like beta2 glycoprotein 1 on the phospholipid cell membrane.

the function of the beta 2 glycoprotein 1is to prevent phospholipid membrane to activate the thrombosis cascade. we know that thrombosis can cause death. so therefore it is very important to checkthe antiphospolipid antibody level. it is especially important in pregnant women,because these antibodies can cause spontaneous abortion and late fetal death. except antiphospholipid antibodies, sle flarescan also cause fetal death. sle fluctuate between flares and remissions. a flare is a very active disease with manysymptoms, whereas a remission is an inactive

state with few symptoms. during pregnancy, the mother should be monitoredfor any sle flares since these can lead to fetal death. so if a woman wants a child, then pregnancyshould be timed for when sle is in remission for at least 6 months. furthermore, anti-ro antibodies should bemeasured, because if anti-ro is detected, then doctors should warn mothers that thereare risks of the fetus getting a neonatal lupus or even a severe congenital heart blockwhich means the death of the fetus. so it is very important to monitor the fetalheart in this case, with for example an echocardiograph

and a 24-hour holter monitor. lets turn now to the biopsy criteria. here we need a biopsy of the kidney, whichwill show that there is inflammation, called nephritis. but it is not enough with a biopsy, we needan immunologic criteria as well, for example antinuclear antibodies, or anti-double-strandeddna. now lets see how we can treat sle patients. the first thing that we have to do is to removeany type of medication that can cause sle-like symptoms.

these are for example hydralazine, procainamide,and isoniazid. non-steroidal anti-inflammatory drugs arevery useful in sle patients, especially in controling arthralgias, which means painfuljoints. here we can use naproxen, ibuprofen, and diclofenac. antimalarial medications also help jointsproblems, but also skin problems, and they reduces the sle flares. the typical sle medication is hydroxychloroquine,but there are alternative like chloroquine and quinacrine. hydroxychloroquine can in rare cases causeretinal problems, skeletal muscle problems

and cardiac problems. so it is important that the eyes are examinedyearly. corticosteroids are usually the first linetreatment in acute severe sle. we typically begin by giving intravenous methylprednisolonefor 3 days and then we maintain the therapy with prednisone. disease-modifying antirheumatic drugs arealso very important. we can use azathioprine, methotrexate, mycophenolatemofetil, cyclophosphamide together with mesna, and in very severe cases intravenous immunoglobulin. it is well known that corticosteroid use fora long time can cause osteoporosis, which

means bone weakening. therefore it is important to consider givingcalcium, vitamin d, and bisphosphonate. so to conclude, we can say that emma has sle,which is a systemic autoimmune disease, that affects her whole body systemically. the brain, skin, heart, lungs, kidneys, joints,the immune system, and the vascular system. the typical butterfly-shaped erythema canbe seen in sle patients. thank you very much for listening!

what is panniculitis

systemic lupus erythematosus, abbreviatedas sle. this is a systemic disease, which means thatit can affect the whole body systemically. the brain, skin, heart, lungs, kidneys, joints,the immune system, the vascular system, and the list goes on. lupus means wolf. erythematosus means reddening of the skin. why did i show a red butterfly? because a very typical sign of sle is a butterflyshaped reddening of the skin. the way i remember this disease, is to imaginea wolf that attacks a woman, and why a woman?

because 9 out 10 patients are women. so the wolf bites the face of the woman causinga butterfly shaped erythema on her face. then the wolf continues to bite all her organsone by one, because this disease is a systemic disease, which means that it can affect allthe organs systemically. of course this disease has nothing to do witha wolf. but sle is an autoimmune disease, which meansthat this woman called emma have an immune system that attacks her own body, insteadof only attacking bacterias, viruses and parasites. so emma have an immune system that acts asa wolf inside her.

i will show you how we can find out if emmareally has sle by diagnosing her. and then we will look at what type of medicationswe can give her. i want you to remember at least one thingfrom this presentation. that is systemic lupus international collaboratingclinics, abbreviated as slicc. slicc is a criterion that can help in thediagnosis of sle. slicc contains clinical criteria, immunologiccriteria and biopsy criteria. we need more than 4 criteria with at least1 clinical and 1 immunologic. or we need 1 biopsy criteria and 1 immunologiccriteria.

so what does these 3 words mean? clinical, immunologic and biopsy? the synonym for clinic, is hospital. so clinical criteria stand for the symptoms,signs and lab values of a patient in the hospital. immunology deals with the immune system thatprotects you from bacterias, viruses, and immunologic criteria are usually lab teststhat detect any problem with the immune system. biopsy means that a doctor cuts out a pieceof an organ. for example, a small piece of kidney can becut out, and then the doctor puts this piece of kidney in a microscope and looks for diseases.

clinical criteria can be divided into alopecia,which means hairloss. skin problemsulcers heart diseaseslung diseases kidney problemsjoint pain problems with the nervous systemand blood diseases. skin problems can be grouped under the namecutaneous lupus erythematosus. we can divide these skin diseases into acutesubacute and chronic, based on the timing of the diseases. acute diseases are usually those that happensuddenly with a short duration.

chronic diseases are ongoing for a long time. whereas subacute means those diseases thatare not yet chronic but has passed the acute phase. a way to remember these timing are to memorize2 numbers. 1 and 3. why? because the duration of acute diseases areusually less than 1 month, subacute are 1 to 3 months, and chronic are more than 3 monthsin duration. so which are the acute type of skin problems?

butterfly erythema, which is a reddening ofthe face in a butterfly shape. it usually affects the cheeks or also calledmalar region, and therefore it is sometimes called malar erythema. it does not affect the nasolabial region. there can also be bullous lesions which areblisters that can be a mix of small grouped vesicles to large tense bullae. bullae are elevating the skin and are filledwith fluid. toxic epidermal necrolysis-like sle, is adetachment of the epidermis, the upperlayer of the skin, resulting in exfoliation, meaningthat the upperlayer just falls off.

this is very dangerous, because the skin isthe organ that protects against infections. so if you loose a large part of your skin,then sepsis can happen, which means that bacterias easily invade your vascular system, sincethere is no skin to protect you. this can lead to something called septic shock,which can lead to death. maculopapular rash is another acute sign. macules are flat spots up to 1 cm, and papulesare bumps up to 1 cm. maculopapular is a combination between maculesand papules. photosensitivity can also be seen which meansthat the skin is much more sensitive to sunlight than normally.

this can cause cause solar urticaria, whichis a vascular reaction of the skin that cause pathches. patches are flat lesions like macules, butthey are bigger than 1 cm. so one difference between macules and patchesis the size. macules are less than 1 cm, whereas patchesare more than 1 cm. so the acute cutaneous lupus erythematosuscan be divided into 5 lesions: butterfly shaped erythema, bullous lesions, toxic epidermalnecrolysis, maculopapular rashes, and photosensitive solar urticarias. subacute cutaneous lupus erythematosus canbe divided into 2 types.

one is annular polycyclic lesions. the word polycyclic refers to more than 1ring structures that can be seen in chemistry for example. the word annular also refers to a ring-shapedstructure. so annular polycyclic lesions are ring-shapedskin lesions that usually occur on sun-exposed areas of the skin. nonindurated psoriaform is the other typeof subacute skin lesions. psoriaform means that it looks like psoriasis. nonindurated means that it is not hardas psoriasis.

subacute can be divided into annular polycyclicand nonindurated psoriaform lesions chronic skin lesions are chilblain lupus,that affects toes, fingers, nose, and ears during cold weather. these are painful, bright red nodules. nodules means a swelling of the skin thatis up to 1 cm diameter. discoid rash can also be seen. discoid refers to the disc shape of theselesions. we can divide discoid into classical type. discoid lesions can be divided into localized,which means that discoid lesions appear above

the neck,and generalized, which means that discoid lesions can appear both above and below theneck. lichen planus is an inflammatory disease thatcan affect the skin and oral mucosa. here we see a picture of whitish lichen planuson the oral mucosa. the word lichen means tree-moss as you cansee here on the picture. so this disease is looking like a tree mossbut with a whitish color. in sle patients this happen, that a discoidlesion is seen together with lichen planus. verrucous lesions or also called hypertrophiclesions are skin that hypertrophies, which means that the skin cells increase in numberand cause these hard wartlike lesions, especially

on extensor arms. mucosal lesions can affect the mucosal membranearound the teeth, the tongue, and hardpalate panniculitis or also called profundus, isan inflammation and destruction of the subcutaneous fat. tumidus lesions are pinkish urticarial non-scarringplaques usually in sun-exposed areas. plaques are elevation of the skin similarto papule, but they differ in size. so plaques are more than 1 cm in diameter,whereas papules are less than 1 cm. the chronic skin lesion are chilblain, discoid,discoid with lichen planus, hypertrophic, mucosal, panniculitis, and tumidus.

ulcers can appear on the mucosal membrane,on for example the hardpalate, buccal region, on the tongue, and on the nasal septum. inflammation can affect the heart causingpericarditis. here we see a normal normal heart on the upperpicture, and a reddish heart on the lower picture. inflammation is causing redness, pain, heat,swelling and loss of function. the heart wall rub against each other causinga typical pericardial rub sound that one can hear with a stethoscope. here we see a man having a painful pericarditispericardial effusion can also happen, which

means that fluid accumulates around the heartcausing a typical waterbottle-shaped heart on x-ray. as i mentioned, pericardial rub sounds canbe heard with a stethoscope. inflammation can also affect the lungs. so similar to the heart, there will be inflammation,pain, pleural friction rub sounds, and pleural effusionhere we can see the pleural effusion that have accumulated between the 2 layers of thelungs. this is how pleural friction rub sounds like. imagine walking on snow when you hear thissound.

we need to collect urine to find kidney problems. more than 500 mg of protein in the urine duringa 24 hour period can be seen in sle patients. this is called proteinuria, meaning proteinin the urine, which is not normal. we can also find red blood cell casts in theurine by analyzing the urine in a microscope. these casts are formed by red blood cellsthat stick together. blood in the urine is not normal. it suggest that something is wrong with thekidney. synovitis is inflammation of the synovialmembrane of the joints. polyarthritis can be seen in sle.

poly stands for that more than 1 joint isaffected. arthritis is inflammation of joint. so more than 1 joint will be inflamed causingpain. the nervous system can also be affected bysle. seizures can happen, which are hyperexcitationof neurons in the brain, sometimes leading to muscle contractions. psychosis and acute confusional state, alsocalled delirium can happen. psychosis and delirium patients usually sufferfrom hallucinations. neuropathies can be seen in sle.

neuropathy means neurons that are diseased. the neurons can be in the cranial part, peripheralpart, in the spinal cord which is then called myelitis, or single nerves can be damagedwhich is then called mononeuropathy, mono standing for single. or multiple single nerves in different areasof the body can be damaged, which is then called multiple mononeuropathy. what can we see in the blood? with a microscope we can distinguish differentblood cells. here is a picture showing the blood cells.

the blood cells originate from one cell calledmultipotential hematopoetic stem cell. this cell can produce myeloid cells, and lymphoidcells. the myeloid cells can produce erythrocytes,also called red blood cells. but in sle hemolytic anemia can be seen, whichmeans that the erythrocytes can damaged and therefore anemia will happen, which meansthat not enough oxygen is transported to the tissues. the myeloid cells can also produce megakaryocytes,that can further produce thrombocytes, also called platelets. but in sle the number of thrombocytes canbe reduced, and we call this thrombocytopenia.

penia stands for less of something, inthis case we have a penia of thrombocytes, so thrombocytopenia. the symptom of thrombocytopenia is usuallypetechiae which are small purplish spots on the skin. leukopenia can happen in sle which is a reducednumber of leukocytes, which are white blood cells, with neutrophils being the most commonwhite blood cell. lymphopenia can also be seen, which are reducednumber of lymphocytes. so the clinical criteria were alopecia, skinlesions, ulcers, diseases of the heart, lungs, kidneys, joints, nervous system and the blood.

the immunologic criteria are related to autoantibodies,meaning that the antibodies of the immune system attacks itself, instead of only attackingbacterias etc. here we have a cell, with its nucleus, containingchromosomes that contain dna. in sle, the antibodies attack your own nuclearproteins, for example your own dna, or rna binding proteins called smith proteins. so in sle we check for antinuclear antibodylevels, abbreviated as ana. we also check anti-smith and anti-double strandeddna. another immunologic criteria is direct coombstest. here we mix the patients blood together witha coombs reagent, and if red blood cells agglutinate,

meaning they stick together, then we havea positive test result. the complement system helps or complementsthe antibodies to fight infections. in sle we can see a low number of these complementproteins. the complement proteins are numbered c1 toc9, and it is the c3 and c4 complement proteins that are low in sle. ch50 stands for the total complement activity,which is also low in sle. an increased number of antiphospholipid antibodiescan be measured in sle. these antibodies bind to proteins like beta2 glycoprotein 1 on the phospholipid cell membrane.

the function of the beta 2 glycoprotein 1is to prevent phospholipid membrane to activate the thrombosis cascade. we know that thrombosis can cause death. so therefore it is very important to checkthe antiphospolipid antibody level. it is especially important in pregnant women,because these antibodies can cause spontaneous abortion and late fetal death. except antiphospholipid antibodies, sle flarescan also cause fetal death. sle fluctuate between flares and remissions. a flare is a very active disease with manysymptoms, whereas a remission is an inactive

state with few symptoms. during pregnancy, the mother should be monitoredfor any sle flares since these can lead to fetal death. so if a woman wants a child, then pregnancyshould be timed for when sle is in remission for at least 6 months. furthermore, anti-ro antibodies should bemeasured, because if anti-ro is detected, then doctors should warn mothers that thereare risks of the fetus getting a neonatal lupus or even a severe congenital heart blockwhich means the death of the fetus. so it is very important to monitor the fetalheart in this case, with for example an echocardiograph

and a 24-hour holter monitor. lets turn now to the biopsy criteria. here we need a biopsy of the kidney, whichwill show that there is inflammation, called nephritis. but it is not enough with a biopsy, we needan immunologic criteria as well, for example antinuclear antibodies, or anti-double-strandeddna. now lets see how we can treat sle patients. the first thing that we have to do is to removeany type of medication that can cause sle-like symptoms.

these are for example hydralazine, procainamide,and isoniazid. non-steroidal anti-inflammatory drugs arevery useful in sle patients, especially in controling arthralgias, which means painfuljoints. here we can use naproxen, ibuprofen, and diclofenac. antimalarial medications also help jointsproblems, but also skin problems, and they reduces the sle flares. the typical sle medication is hydroxychloroquine,but there are alternative like chloroquine and quinacrine. hydroxychloroquine can in rare cases causeretinal problems, skeletal muscle problems

and cardiac problems. so it is important that the eyes are examinedyearly. corticosteroids are usually the first linetreatment in acute severe sle. we typically begin by giving intravenous methylprednisolonefor 3 days and then we maintain the therapy with prednisone. disease-modifying antirheumatic drugs arealso very important. we can use azathioprine, methotrexate, mycophenolatemofetil, cyclophosphamide together with mesna, and in very severe cases intravenous immunoglobulin. it is well known that corticosteroid use fora long time can cause osteoporosis, which

means bone weakening. therefore it is important to consider givingcalcium, vitamin d, and bisphosphonate. so to conclude, we can say that emma has sle,which is a systemic autoimmune disease, that affects her whole body systemically. the brain, skin, heart, lungs, kidneys, joints,the immune system, and the vascular system. the typical butterfly-shaped erythema canbe seen in sle patients. thank you very much for listening!

erythema nodosum and lupus

with vasculitis, you have “inflammation”,of the “blood vessels”, and even though this can happen in arteries or veins, we’regoing to focus on vasculitis in arteries because it’s way more common. vasculitides are categorizedby the size of the blood vessels they affect, so we have small-vessel, medium-vessel, andlarge-vessel vasculitis. typically vasculitis is due to an autoimmune disease, where theimmune system confuses a part of normal body as a foreign invader, and there are a coupleof ways this might happen. sometimes the body confuses the innermostlayer of the blood vessel, which is the endothelial layer, with a foreign pathogen and directlyattacks it. to be a little more specific, the white blood cells of the immune systemmix up the normal antigens on the endothelial

cells with the antigens of foreign invaderslike bacteria simply because they look similar - this is called molecular mimicry. this autoimmuneconfusion is thought to be the cause several types of medium-vessel and large-vessel vasculitides. other times the immune system attacks healthycells that are near the vascular endothelium, and the endothelial cells are only gettingindirectly damaged. this is the situation in many small-vessel vasculitides, where theimmune system attacks white blood cell enzymes or other non-endothelial cell targets. once the endothelium is damaged either directlyor indirectly, almost all vasculitis diseases progress in a similar way. the damaged endotheliumexposes the underlying collagen and tissue

factor, and these exposed materials increasethe chance of blood coagulation. the blood vessel walls themselves get weaker as theyare damaged, making aneurysms more likely. and finally as the vessel wall heals, it becomesharder and stiffer because fibrin is deposited into the blood vessel walls as part of thehealing process. and actually, that’s vasculitis in a nutshell.the different types of vasculitis for the most part only vary depending on how theyare triggered and where in the body they cause problems. people with vasculitis have generalized symptomscaused by the inflammatory response of the immune system. symptoms like fever, weightloss, fatigue, etc. more specific symptoms

occur usually based off where in body thevasculitis is occurring, and which organ is supplied by that blood vessel. reduced bloodflow caused by vasculitis can cause organ ischemia which can happen in two ways. first,blood cells clump onto the exposed tissue factor and collagen on the inside of bloodvessels forming blood clots that and can restrict blood flow. the second way is caused by thehealing process of the blood vessel. as fibrin is deposited in the vessel wall, the wallsbecome thicker and bulge into the vessel, reducing the diameter of the vessel lumen. alright, now that we have the general ideaof vasculitis covered, let’s take a look at some specific conditions, starting withthe large-vessel vasculitides.

giant cell arteritis is a vasculitis thataffects branches of the carotid arteries. vasculitis in the temporal branch of the carotidartery is the most common location and causes headaches. vasculitis in the ophthalmic arterycan cause visual disturbances, and vasculitis in any of the arteries that supply the jawmuscles can cause pain when someone chews food - called claudication. giant cell arteritisaffects older individuals (typically more than 50 years old) and women more than men,so a grandmother would be in a high-risk group. classically, this type of vasculitis causeslots of inflammation and it results in a really high erythrocyte sedimentation rate (or esrfor short) - sometimes over 100! in giant cell arteritis, a biopsy of the affected arterywill show giant cells embedded in the internal

elastic lamina, which is a thin layer of elastictissue that separates the tunica intima and the tunica media. to be clear, these giantcells are actually not individual cells at all, but rather granulomas - a group of monocytesthat are packed tightly together, and look like one giant cell. now giant cell arteritisis segmental, which means that if you look at the entirety of an affected artery, you’llsee only sections of the artery are actually affected. this means that when biopsies aredone, you have to take a long section of the artery and examine it under a microscope.it also means that, if you don’t see any affected tissue, you can’t for sure ruleout the disease because it’s possible you took an unaffected section of the blood vessel.you can treat people with giant cell artertitis

by giving them corticosteroids, which weakensthe immune response. people whose ophthalmic artery is affected and don’t receive treatmentare at a high risk of blindness, again because poor blood flow to the eyes causes ischemiaand irreversible blindness. alright, so another large-cell vasculitisis called takayasu arteritis, and it’s very similar to giant cell arteritis except fortwo key differences. one is that it usually affects asian women that are under 40 yearsold where giant cell arteritis usually affects people over the age of 60. and two, it affectsthe arteries that branch off from the aortic arch, particularly around the branch points.if the inflammation occurs around aortic branches that serve the upper extremities, it causesa weak or nonexistent pulse. if the inflammation

occurs around the aortic branch that servesthe head, then it causes visual and neurological symptoms. histopathologically it’s quitesimilar to giant cell arteritis because in takayasu arteritis you still see giant cellsand granulomatous inflammation in the internal elastic lamina of the blood vessel. in addition,the erythrocyte sedimentation rate will be elevated, and takayasu arteritis is treatedwith corticosteroids. let’s move onto medium-vessel vasculitisdiseases. these vasculitis diseases typically affect a wide range of muscular arteries thatsupply organs, which gives the conditions a wide range of possible symptoms. the mostcommon type of all vasculitides is kawasaki disease, and we’ve got a separate videoon kawasaki disease, but for now it’s important

to note that it affects the coronary arteries,the muscular arteries serving the heart. next there’s polyarteritis nodosa, whichis thought to occur when the immune cells directly attack the endothelium, confusingit with hepatitis b virus. now, polyarteritis nodosa causes transmural inflammation, whichmeans the entire wall, the tunica intima, media, and adventitia are all affected. thisinflammation causes the vascular wall to die through all three layers of the artery andfibrosis occurs as the vascular wall heals, this process is called fibrinoid necrosis.the fibrosed vessel wall is left weak and prone to aneurysms, so some areas start tobulge out through the weakened walls. so if you step back and look at the artery you seethese fibrotic aneurysms which are hard bulges

down the length of the artery, and they looklike a “string of beads” on angiogram. this pattern is quite unique among the variousvasculitides. organ ischemia in the distribution of affected arteries is the main complication.if the renal arteries are affected, then a person will have hypertension (remember kidneysregulate blood volume). if the mesenteric artery is affected, a person can have mesentericischemia and severe abdominal pain and gastrointestinal bleeding. if the arteries affecting the brainare affected it can cause neurological symptoms, and if arteries supply the skin are affectedthen it can lead to skin lesions. treatment is aimed at reducing the vessel inflammationand generally includes corticosteroids. another medium-vessel vasculitis is buerger’sdisease, named for a nyc pathologist not a

hamburger. it’s other name is thromboangiitisobliterans, which literally translates to clot vessel inflammation blockage, and asthe name suggests this vasculitis is notoriously for causing blood clots in tiny arteries inthe fingers and toes, which leads to ulcers and eventually dead tissue in these digitsand eventual autoamputation. not fun. buerger’s disease typically affects men between theages of 20-40 years and the biggest risk factor for this vasculitis is the use of tobaccoproducts. in fact, the thought is that tobacco might be the trigger for the autoimmune responseagainst blood vessel. stopping the use of tobacco actually slows down (but doesn’tnecessarily stop) the disease and need for amputations in most patients.

alright onto small-vessel vasculitis. small-vesselvasculitis affects small vessels like arterioles, capillaries, and venules. in the diseases,b-cells mistakenly target their antibodies to granules made by a person’s own neutrophils.in a sense, one immune cell attacking another. the antibodies are called “anti-neutrophiliccytoplasmic antibodies” or ancas for short and they are mainly of the igg type. the disease granulomatosis with polyangiitis(gpa) which used to be called wegener’s granulomatosis, is one of these small vesselvasculitides. the b-cells release an autoantibody called cytoplasmic antineutrophil cytoplasmicantibody or c-anca. yep, the name is hilariously redundant - with cytoplasmic included twiceto drive home the point. c-anca targets and

bind to a specific neutrophil granule calledproteinase 3 which is embedded in the membrane of some neutrophils. once c-anca binds tothe neutrophil, it causes the neutrophil to release oxygen free radicals, which enterthe nearby endothelial cells damaging them indirectly and causing vasculitis. on a biopsy,you can see evidence of inflammation and granulomas in the blood vessel wall. gpa affects thenasopharynx, lungs, and kidneys and usually occurs in middle-aged males. people with thedisease can have chronic pain caused by sinusitis or bloody mucus from ulcers within the nose.over time, the nose itself may even cave in or curl, a condition called a saddle nosedeformity. blood vessel inflammation in the lungs and air passages can also make breathingmore difficult causing air passages to constrict,

and ulcers can form causing bloody coughing.in the kidneys, the inflammation restricts blood flow to the glomeruli, causing themto die and leading to decreased urine production and an increase in blood pressure since thekidneys are no longer as efficient at regulating blood volume. gpa is typically treated withcorticosteroids and cyclophosphamide, but relapses in the disease are common, and thatmakes sense. the presence of c-anca is the main cause of the disease, and if it keepsattacking the granules from within neutrophils, there is a good chance the disease will return. another small-vessel vasculitis that is verysimilar to granulomatosis with polyangiitis is microscopic polyangiitis. it’s so similarin fact, that you need to rely on some clues

to help distinguish them. microscopic polyangiitisdoes not affect the blood vessels of the nose/sinuses, only the kidneys and lungs. you also won’tsee the granulomas in the blood vessel walls like you would in granulomatosis with polyangiitis.the third difference is you won’t find c-anca antibodies. instead you’ll find p-anca antibodies(the p stand for perinuclear), which is just a different type of anti-neutrophilic cytoplasmicantibody reacting with the neutrophil granule myeloperoxidase instead of proteinase 3. youtreat microscopic polyangiitis the same way you treat granulomatosis with polyangiitis,corticosteroids and cyclophosphamide, and it’s also common for it to relapse. churg-strauss syndrome is very similar toboth granulomatosis with polyangiitis and

microscopic polyangiitis. it too is causedby p-anca antibodies and it causes similar symptoms such as sinusitis, lung damage, andkidney damage, but it also causes gastrointestinal, skin, nerve, and heart damage like some medium-vesselvasculitis diseases. a lot of the time churg-strauss syndrome ismistaken as allergies and asthma because they all have similar symptoms. that, and likeallergies and asthma, churg-strauss causes a lot of eosinophils to float around in theblood. actually people who have asthma and peripheral eosinophilia are more likely todevelop churg-strauss syndrome because they both have elevated eosinophils. also justlike granulomatosis with polyangiiti, granulomas can form.

next up, henoch-schonlein purpura. now unlikethe other small vessel vasculitis diseases we’ve talked about henoch-schonlein purpura(abbreviated at hsp) doesn’t involve anca antibodies. instead, we find elevated levelsof the iga antibodies floating around in the blood. now iga is an awesome antibody thatis found in our mucosal cells, which are cells that are in some way exposed to the outsideworld, for example cells in our lungs and our gastrointestinal tract. in hsp, the person starts making iga thatis directly targeted at their own endothelial cells because of molecular mimicry. this goesagainst the general trend of small-vessel vasculitides being the result of indirectdamage. symptoms depend on where the iga-mediated

attack on small blood vessels happens. sometypical places is the skin blood vessels around the buttocks and legs, which leads to significantskin discolouration that looks like blood is pooling under the skin surface - calledpurpura. one indication that the disease is henoch-schonlein is that the skin discolorationis palpable, as in you can feel it raise above the normal skin. remember the fibrosis ofthe blood vessel walls hardens and makes it palpable, just like in polyarteritis nodosa.if the iga attacks the blood vessels in the gastrointestinal tract it can cause abdominalpain, and if it attacks the blood vessels in the kidneys, it can lead to hematuria (bloodin the urine) and eventually affect the kidney’s function which is called iga nephropathy.

just like the other small-vessel vasculitisdiseases, henoch-schonlein purpurpa resolves on its own but it can reoccur. generally itis only treated with steroids if the symptoms are severe. and there you go! that’s vasculitis!