Antisynthetase Syndrome

Antisynthetase syndrome — Up to 30 percent of patients with DM or PM have a constellation of clinical findings termed the "antisynthetase syndrome" . These findings include relatively acute disease onset, constitutional symptoms (eg, fever and weight loss), myositis, the Raynaud phenomenon, mechanic's hands, arthritis that is generally nonerosive, and ILD . Affected patients have antibodies to aminoacyl-transfer ribonucleic acid (tRNA) synthetase enzymes; the presence of one of these antibodies is highly specific for DM, PM, or ILD .

This syndrome can be further characterized as follows:

●Not all patients with antisynthetase antibodies or even those classified as having the antisynthetase syndrome have all manifestations of this syndrome. The syndrome is generally considered present in patients with an antisynthetase antibody plus two of the following features, which are elements of the syndrome: ILD, inflammatory myopathy, and inflammatory polyarthritis.

●This group of clinical findings or this general clinical picture is not specific for antisynthetase antibodies. Patients with other types of autoantibodies (eg, anti-PM-Scl or anti-U1 ribonucleoprotein [RNP] antibodies) can also present with these types of features. However, patients with antisynthetase antibodies generally have more prominent or severe myositis and ILD, and they usually lack some of the other clinical features seen in patients with these other autoantibodies.

●Some patients with antisynthetase antibodies have relatively little or no myositis, while ILD or other features are more prominent. The absence of myositis is seen more often with some antisynthetase antibodies than with others.

Bhopalwala. H

DM - PM (Abs associated with Malignancy)

Serum autoantibodies — Some serum antibodies in DM and PM confer a positive risk of malignancy, whereas others are associated with a negative risk.

●Positive risk – "Cancer-associated myositis" (CAM) in adults has been associated in several studies with antibodies to transcription intermediary factor (TIF)-1gamma (anti-p155, anti-p155/140) and with antibodies to nuclear matrix protein (NXP)-2 (anti-MJ or anti-p140) .

●Negative risk – Conversely, the presence of myositis-specific (anti-synthetase antibodies, anti-Mi-2, anti-SRP) and myositis-associated antibodies (anti-RNP, anti-PM-Scl, anti-Ku) appears to be associated with a decreased risk of malignancy but an increased risk of interstitial lung disease in DM . More study is required to determine the utility of these autoantibodies for cancer screening in patients with myositis.

Around 30% of patients with Dermatomyositis develop Malignancy.

Around 5% of patients with Polymyositis develop malignancy.

Bhopalwala. H

Irregularly irregular rhythms

Quiz: Name the three types of irregularly irregular rhythms.

Answer:

Atrial fibrillation

Multifocal atrial tachycardia

Atrial flutter with variable conduction

That's all!

-IkaN

Baricitinib (Olumiant)

Mechanism of Action

Baricitinib inhibits Janus kinase (Jak) enzymes, which are intracellular enzymes involved in stimulating hematopoiesis and immune cell function through a signaling pathway. In response to extracellular cytokine or growth factor signaling, Jaks activate signal transducers and activators of transcription (STATs), which regulate gene expression and intracellular activity. Inhibition of Jaks prevents the activation of STATs and reduces serum IgG, IgM, IgA, and C-reactive protein

Use

Rheumatoid arthritis: Treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor antagonist therapies.

Limitation of use: Use of baricitinib in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

Bhopalwala. H

Certolizumab (Cimzia)

Mechanism of Action

Certolizumab is a pegylated humanized antibody Fab’ fragment of tumor necrosis factor alpha (TNF-alpha) monoclonal antibody. Certolizumab binds to and selectively neutralizes human TNF-alpha activity. (Elevated levels of TNF-alpha have a role in the inflammatory process associated with Crohn disease and in joint destruction associated with rheumatoid arthritis.) Since it is not a complete antibody (lacks Fc region), it does not induce complement activation, antibody-dependent cell-mediated cytotoxicity, or apoptosis. Pegylation of certolizumab allows for delayed elimination and therefore an extended half-life

Use :

Ankylosing spondylitis: Treatment of adults with active ankylosing spondylitis (AS)

Crohn disease: Treatment of moderately to severely active Crohn disease in patients who have inadequate response to conventional therapy

Plaque psoriasis: Treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy

Psoriatic arthritis: Treatment of adult patients with active psoriatic arthritis

Rheumatoid arthritis: Treatment of adults with moderately to severely active rheumatoid arthritis (RA) (as monotherapy or in combination with nonbiological disease-modifying antirheumatic drugs [DMARDS])

Bhopalwala. H

Classification Criteria for Rheumatoid Arthritis

2010 ACR/EULAR criteria —

Using the 2010 ACR/EULAR classification criteria for RA, classification as definite RA is based upon the presence of synovitis in at least one joint, the absence of an alternative diagnosis that better explains the synovitis, and the achievement of a total score of at least 6 (of a possible 10) from the individual scores in four domains . The highest score achieved in a given domain is used for this calculation. These domains and their values are:

●Number and site of involved joints

•2 to 10 large joints (from among shoulders, elbows, hips, knees, and ankles) = 1 point

•1 to 3 small joints (from among the metacarpophalangeal joints, proximal interphalangeal joints, second through fifth metatarsophalangeal joints, thumb interphalangeal joints, and wrists) = 2 points

•4 to 10 small joints = 3 points

•Greater than 10 joints (including at least 1 small joint) = 5 points

●Serological abnormality (rheumatoid factor or anti-citrullinated peptide/protein antibody)

•Low positive (above the upper limit of normal [ULN]) = 2 points

•High positive (greater than three times the ULN) = 3 points

●Elevated acute phase response (erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP]) above the ULN = 1 point

●Symptom duration at least six weeks = 1 point

In addition to those with the criteria above, which are best suited to patients with newly presenting disease, the following patients are classified as having RA:

●Patients with erosive disease typical of RA with a history compatible with prior fulfillment of the criteria above

●Patients with longstanding disease, including those whose disease is inactive (with or without treatment) who have previously fulfilled the criteria above based upon retrospectively available data

Fun fact : Hand ultrasound is done to evaluate for inflammation in RA, if it's not clinically evident.

Bhopalwala. H

SLE vs RA

The arthritis in SLE may look very similar to RA.

The main difference is that it is non erosive, unlike RA.

Pearls of wisdom :

When treating chronic conditions like Rheumatoid Arthritis, Osteoarthritis, SLE, Fibromyalgia, Psoriasis, and Psoriatic Arthritis, you've got to involve the patient in the care. You've got to explain to them that these are  chronic conditions with no cure. Goals should be damage control and remission.

A good strong patient doctor relationship when dealing with these conditions, works better than any pill on planet Earth.

Credits : Dr.G

Bhopalwala. H

Discoid Lupus Erythematosus

Discoid lupus erythematosus — It is estimated that 15 to 30 percent of patients with SLE develop DLE . Patients with localized or generalized DLE are estimated to have cross-sectional prevalences of concurrent SLE between 5 and 28 percent.

The presence of DLE lesions among patients with SLE may modify the risk of specific SLE features. Compared with SLE patients without DLE, those with DLE have increased risk for photosensitivity and leukopenia but decreased risk for serositis and arthritis. There is no obvious change in risk of nephritis despite variable reports of a "renal-protective effect" of the presence of discoid lesions among SLE patients.

Data on the risk for progression of DLE to SLE are limited to retrospective cohort studies, studies lacking power to detect statistical significance of potential markers of progression, and studies that do not address DLE specifically as a CLE subset. In these studies, progression to SLE has occurred in 0 to 28 percent of patients initially presenting with DLE . Progression to SLE often is delayed; in a Swedish-based population cohort study, 10 percent of patients with DLE who subsequently developed SLE did so within the first year and 17 percent developed SLE within the first three years . Two retrospective studies have suggested SLE develops within five years in 50 percent of the DLE patients who indeed go on to develop SLE . Risk factors for progression include an increasing number of clinical and serologic features of SLE: more widespread DLE lesions, arthralgias and arthritis, high antinuclear antibody (ANA) titers, leukopenia, and high erythrocyte sedimentation rates .

It is worth noting that patients with DLE and other mucocutaneous manifestations of LE may meet ACR classification criteria for SLE without having other end-organ disease . Revised classification criteria (the SLICC criteria) have been proposed to address some limitations of the ACR criteria.

●Clinical manifestations – The classic findings of DLE are discrete, erythematous, somewhat indurated plaques covered by a well-formed adherent scale that extends into dilated hair follicles (follicular plugging). The plaques tend to expand slowly with active inflammation at the periphery and then heal, leaving depressed central scars, atrophy, telangiectasias, and hyperpigmentation and/or hypopigmentation . DLE most often involves the face, neck, and scalp but may also occur on the ears (particularly conchal bowls) and, less frequently, on the upper torso . Localized DLE is limited to sites above the neck. Generalized DLE refers to DLE occurring both above and below the neck.

Hypertrophic DLE is an uncommon clinical variant of DLE characterized by the development of hyperkeratotic, verrucous plaques

Fun Fact : SEAL, the famous singer suffers from DLE.

https://en.m.wikipedia.org/wiki/Kiss_from_a_Rose

Bhopalwala. H

Clinical Indications for Thalidomide

Use :

Erythema nodosum leprosum: Acute treatment of cutaneous manifestations of moderate to severe erythema nodosum leprosum; maintenance treatment for prevention and suppression of cutaneous manifestations of erythema nodosum leprosum recurrence

Limitation of use: Thalidomide is not indicated as monotherapy for erythema nodosum leprosum treatment in the presence of moderate to severe neuritis.

Multiple myeloma: Treatment of newly diagnosed multiple myeloma (in combination with dexamethasone)

Mechanism of Action :

Thalidomide exhibits immunomodulatory and antiangiogenic characteristics; immunologic effects may vary based on conditions. Thalidomide may suppress excessive tumor necrosis factor-alpha production in patients with erythema nodosum leprosum, yet may increase plasma tumor necrosis factor-alpha levels in HIV-positive patients. In multiple myeloma, thalidomide is associated with an increase in natural killer cells and increased levels of interleukin-2 and interferon gamma. Other proposed mechanisms of action include suppression of angiogenesis, prevention of free-radical-mediated DNA damage, increased cell mediated cytotoxic effects, and altered expression of cellular adhesion molecules.

Fun fact : Thalidomide causes congenital defects called phocomelia.

Bhopalwala. H

Labs in SLE

Laboratory testing — We obtain the following routine laboratory tests, which may provide diagnostically useful information:

●Complete blood count and differential may reveal leukopenia, mild anemia, and/or thrombocytopenia

●Elevated serum creatinine may be suggestive of renal dysfunction

●Urinalysis with urine sediment may reveal hematuria, pyuria, proteinuria, and/or cellular casts

In addition to the routine laboratories described above, we perform the following laboratory tests which support the diagnosis of SLE if abnormal:

●ANA

●Antiphospholipid antibodies (lupus anticoagulant [LA], IgG and IgM anticardiolipin [aCL] antibodies; and IgG and IgM anti-beta2-glycoprotein [GP] I)

●C3 and C4 or CH50 complement levels

●Erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) levels

●Urine protein-to-creatinine ratio

The ANA test is positive in virtually all patients with SLE at some time in the course of their disease . If the ANA is positive, one should test for other specific antibodies such as dsDNA, anti-Sm, Ro/SSA, La/SSB, and U1 ribonucleoprotein (RNP). In some labs, a positive ANA test by indirect immunofluorescence will automatically result in testing for such additional antinuclear antibodies that are often present in patients SLE.

●Anti-dsDNA and anti-Sm antibodies are highly specific for SLE, but anti-Sm antibodies lack sensitivity . Anti-dsDNA and anti-Sm antibodies are seen in approximately 70 and 30 percent of patients with SLE, respectively.

●Anti-Ro/SSA and anti-La/SSB antibodies are present in approximately 30 and 20 percent of patients with SLE, respectively; however, both antibodies are more commonly associated with Sjögren's syndrome.

●Anti-U1 RNP antibodies are observed in approximately 25 percent of patients with SLE, but they also occur in patients with other conditions and high levels are almost always present in patients with mixed connective tissue disease (MCTD).

●Antiribosomal P protein antibodies have a high specificity for SLE, but have low sensitivity for SLE. They also lack specificity for involvement of a particular organ system or disease manifestation.

If the initial ANA test is negative, but the clinical suspicion of SLE is high, then additional antibody testing may still be appropriate. This is partly related to the differences in the sensitivity and specificity among the methods used to detect ANA. A more detailed discussion on the techniques used to detect ANA is presented separately.

Fun fact : Anti-Sm antibody was actually named after a patient with Lupus, Mr. Smith.

Bhopalwala. H

Secukinumab (Cosentyx)

Use :

Ankylosing spondylitis: Treatment of active ankylosing spondylitis in adults.

Plaque psoriasis: Treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

Psoriatic arthritis: Treatment of active psoriatic arthritis in adults.

Mechanism of Action :

Secukinumab is a human IgG1 monoclonal antibody that selectively binds to the interleukin-17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine involved in normal inflammatory and immune responses. Secukinumab inhibits the release of proinflammatory cytokines and chemokines.

Never treat a test, test the patient always #Dr. G

Bhopalwala. H

Ixekizumab (Taltz)

Use

Plaque psoriasis: Treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.

Psoriatic arthritis: Treatment of active psoriatic arthritis in adult patients.

Mechanism of Action :

Ixekizumab is a humanized IgG4 monoclonal antibody that selectively binds with the interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory cytokines and chemokines.

Bhopalwala. H

Belimumab ( Benlysta)

Mechanism of Action :

Belimumab is an IgG1-lambda monoclonal antibody that prevents the survival of B lymphocytes by blocking the binding of soluble human B lymphocyte stimulator protein (BLyS) to receptors on B lymphocytes. This reduces the activity of B-cell mediated immunity and the autoimmune response.

Use :

Systemic lupus erythematosus: Treatment of adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard therapy.

Limitations of use: Use is not recommended in patients with severe active lupus nephritis, severe active CNS lupus, or in combination with other biologics, including B-cell targeted therapies or intravenous (IV) cyclophosphamide.

Bhopalwala. H

Guttate Psoriasis

The papules and plaques of guttate psoriasis are usually less than 1 cm in diameter (giving rise to the name guttate, which means drop-like). The trunk and proximal extremities are the primary sites of involvement.

Guttate psoriasis typically occurs as an acute eruption in a child or young adult with no previous history of psoriasis. Less commonly, a guttate psoriatic flare occurs in a patient with preexisting psoriasis. There is a strong association between recent infection (usually streptococcal pharyngitis) and guttate psoriasis

Bhopalwala. H

Pustular Psoriasis

Pustular psoriasis — Pustular psoriasis is a form of psoriasis that can have life-threatening complications. The most severe variant (the von Zumbusch type of generalized pustular psoriasis) presents with the acute onset of widespread erythema, scaling, and sheets of superficial pustules . This form of psoriasis can be associated with malaise, fever, diarrhea, leukocytosis, and hypocalcemia. Renal, hepatic, or respiratory abnormalities and sepsis are potential complications.

Reported causes of pustular psoriasis include pregnancy (impetigo herpetiformis), infection, and the withdrawal of oral glucocorticoids. The term impetigo herpetiformis has been used to refer to pustular psoriasis of pregnancy.

Bhopalwala. H

Inverse Psoriasis

Inverse psoriasis — "Inverse psoriasis" refers to a presentation involving the intertriginous areas, including the inguinal, perineal, genital, intergluteal, axillary, or inframammary regions . This presentation is called "inverse" since it is the reverse of the typical presentation on extensor surfaces. This variant can easily be misdiagnosed as a fungal or bacterial infection since there is frequently no visible scaling.

Bhopalwala. H

Grading of Sacroiliitis on Imaging

Plain radiographs of the sacroiliac (SI) joints can be semiquantitatively graded based upon the presence of the characteristic radiographic findings :

●Grade 0: Normal .

●Grade 1: Suspicious changes .

●Grade 2: Minimal abnormality – Small localized areas with erosions or sclerosis, without alteration in the joint width . Erosions usually first appear on the iliac side.

●Grade 3: Unequivocal abnormality – Moderate or advanced sacroiliitis with erosions, evidence of sclerosis, widening, narrowing, or partial ankylosis .

●Grade 4: Severe abnormality – Total ankylosis

Bhopalwala. H

Classification Criteria for Axial Spondyloarthritis

Axial SpA — Classification criteria for axial SpA, including criteria for those without plain radiographic changes (nonradiographic axial SpA [nr-axSpA]) and with radiographic (radiographic axial SpA) changes of sacroiliitis, were based upon a large multicenter study [39]. In patients with a history of back pain of unknown origin, which was of at least three months' duration and which began before age 45, the classification criteria for axial SpA exhibited sensitivity of 83 percent and specificity of 84 percent [39]. This algorithm is as follows:

●The entry step is that the patient must have had back pain of any type for at least three months, and the age of onset must be less than 45 years.

●The second step consists of two arms that are evaluated separately based upon the presence either of sacroiliitis on imaging or of human leukocyte antigen (HLA)-B27:

•HLA-B27-positive patients – In patients who test positive for HLA-B27, at least two additional features of SpA from the list below are required for classifying a patient as having axial SpA (see 'SpA features' below)

•Sacroiliitis on imaging – In patients diagnosed with sacroiliitis based upon plain radiographs (structural changes) or magnetic resonance imaging (MRI) (subchondral bone marrow edema [BME]), at least one other feature of SpA from the list below should be present (see 'SpA features' below)

SpA features — The following are SpA features that contribute to the classification criteria for axial SpA (see 'Axial SpA' above):

●Inflammatory back pain – Several definitions for inflammatory back pain have been proposed. For classification purposes, inflammatory back pain can be defined as having at least four of the five following parameters [67]:

•Age of onset <40 years

•Insidious onset

•Improvement with exercise

•No improvement with rest

•Pain at night (with improvement upon arising)

●Other SpA features (each of equal weight) – Other SpA features include the presence of one or more of the non-spinal features noted below. The occurrence can be either before or at the time of evaluation for the following items listed: arthritis, heel enthesitis, uveitis, dactylitis, psoriasis, and inflammatory bowel disease. The features are:

•Arthritis – As diagnosed by a clinician

•Heel enthesitis – Spontaneous pain or tenderness at site of insertion of Achilles tendon or plantar fascia at the calcaneus diagnosed by a clinician

•Uveitis – Confirmed by an ophthalmologist

•Dactylitis – Diagnosed by a clinician

•Psoriasis – Diagnosed by a clinician

•Inflammatory bowel disease – Crohn disease or ulcerative colitis diagnosed by a clinician

•Good response to nonsteroidal antiinflammatory drugs (NSAIDs) – Within 24 to 48 hours

•Family history of SpA – Presence in first- or second-degree relatives of AS or acute anterior uveitis [37]

•Elevated C-reactive protein (CRP) – After exclusion of other causes for elevated CRP

Bhopalwala. H

Classification Criteria for Peripheral Spondyloarthritis

For classification as having peripheral SpA, the patient should NOT have concurrent inflammatory back pain. In that case, the axial SpA criteria should be used. However, inflammatory back pain in the past is considered as a contributing SpA feature. There are two steps in the algorithm for classifying peripheral SpA:

The entry step is that the patient should have, at the time of being seen, at least one of the following three findings:

●Arthritis

●Enthesitis (spontaneous pain or tenderness at any enthesis)

●Dactylitis

If the patient satisfies the entry criteria, the patient should show (or have had in the past) at least one of the features of SpA in Group A (below) or at least two of the features of SpA in group B (below):

●Group A SpA features:

•Uveitis – Confirmed by an ophthalmologist

•Psoriasis – Diagnosed by a clinician

•Crohn disease or ulcerative colitis – Diagnosed by a clinician

•Preceding infection – Urethritis/cervicitis or diarrhea within one month prior to onset of arthritis/enthesitis/dactylitis

•HLA-B27

•Sacroiliitis on imaging

●Group B SpA features:

•Arthritis – Diagnosed by a clinician

•Enthesitis – Diagnosed by a clinician

•Dactylitis – Diagnosed by a clinician

•Inflammatory back pain in the past

•Family history of SpA – Presence in first- or second-degree relatives of AS and acute uveitis

Bhopalwala. H

How to Define Inflammatory Back Pain

●Inflammatory back pain – Several criteria have been proposed for defining IBP ; we use the "ASAS [Assessment of SpondyloArthritis International Society] expert criteria" to identify patients with IBP . The criteria for IBP are met if at least four of the following five features are present and IBP is described as "suggested" in the presence of three of five features:

•Onset of back discomfort before the age of 40 years

•Insidious onset

•Improvement with exercise

•No improvement with rest

•Pain at night (with improvement upon arising)

The presence of four of the five features listed above has a sensitivity and specificity of 80 and 74 percent, respectively, for an inflammatory cause of the back pain among patients with chronic back pain of unclear origin and onset of the back pain at <45 years of age who were evaluated by local rheumatologists . However, when IBP is present, and considered independently of other factors, the probability of AS among patients with chronic back pain increases only from 5 percent to 14 to 16 percent .

Bhopalwala. H

Rhupus

Rhupus – The term rhupus has been used to describe patients with overlapping features of both SLE and RA. Whether rhupus is clinically and immunologically a distinct entity, a true overlap of SLE and RA, or a subset of patients with SLE remains a matter of debate. In addition to having serologies consistent with both SLE and RA, some patients classified as rhupus may have an erosive arthropathy that is atypical for SLE

Bhopalwala. H