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