Subnormal values — Extremely low serum alkaline phosphatase concentrations can be seen in patients with fulminant Wilson disease complicated by hemolysis .
Low values can also occur in patients with hypothyroidism, pernicious anemia, zinc deficiency, congenital hypophosphatemia, and certain types of progressive familial intrahepatic cholestasis in children.
Bhopalwala. H
The final 1990 ACR FM classification criteria included:
●Symptoms of widespread pain, occurring both above and below the waist and affecting both the right and left sides of the body
●Physical findings of at least 11 of 18 defined tender points
These simple criteria had greater than 85 percent sensitivity and specificity for differentiating patients with FM from those with other rheumatic diseases.
In office practice, the diagnosis of FM can be made even if fewer than 11 of 18 tender points are present, provided that the history is consistent with FM and that the major differential diagnoses have been excluded . The tender points represent heightened pain perception rather than sites of inflammation or tissue pathology. Thus, they are proxies for detecting widespread pain, and the exact number necessary to diagnose FM clinically is somewhat arbitrary. It is important to recognize that the classification criteria were validated for large patient populations and should be used primarily in clinical research and epidemiologic studies of FM
Bhopalwala. H
Beighton score for joint hypermobility —
JHM should be evaluated in all patients suspected of JHS. JHM is ascertained by determination of their Beighton score, which depends on the presence of JHM in the hands, elbows, lumbar spine, and knees using specific examination techniques . One point is awarded for the ability to perform each of nine maneuvers (including four maneuvers tested bilaterally and evaluation of the spine). A score of 4 or more points represents generalized hypermobility. The specific maneuvers include:
●Passive apposition of the thumb to the volar aspect of the ipsilateral forearm
●Passive hyperextension of fingers, demonstrated by passive dorsiflexion of the fifth metacarpophalangeal joint to at least 90 degrees
●Hyperextension of the elbow to at least 10 degrees
●Hyperextension of the knee to at least 10 degrees
●Flexion of the spine with placement of the palms flat on the floor without bending the knees
The presence of JHM can be documented by an examination limited to those areas required for calculating the Beighton score, but an examination for JHM and joint stability that is adequate for fuller assessment of the patient and the formulation of treatment plans should also encompass the other joints, including the temporomandibular joints, shoulders, hips, cervical and thoracic spine, ankles, and feet.
In addition to determination of the Beighton score based upon the examination, the presence of generalized JHM, including its presence historically, may also be suspected in patients who answer ‘yes’ to two or more questions in a simple five-part questionnaire :
●Can you now (or could you ever) place your hands flat on the floor without bending your knees?
●Can you now (or could you ever) bend your thumb to touch your forearm?
●As a child did you amuse your friends by contorting your body into strange shapes OR could you do splits?
●As a child or teenager did your shoulder or kneecap dislocate on more than one occasion?
●Do you consider yourself double-jointed?
Bhopalwala. H
Bohan and Peter in 1975 defined DM and PM based upon the following features :
●Symmetric proximal muscle weakness
●Typical cutaneous eruption of DM (the only feature distinguishing DM from PM)
●Elevated serum muscle enzymes
●Myopathic changes on EMG
●Characteristic muscle biopsy abnormalities and the absence of histopathologic signs of other myopathies
Patients with the cutaneous eruption and at least three of the other four criteria met the requirements for definite DM according to these criteria, while requirements for definite PM were met by those with all four criteria other than the cutaneous features . Patients with findings indicating the presence of other disorders that may present similarly were excluded. Patients who did not meet these criteria but who lacked any of the exclusions could potentially have been diagnosed with possible or probable DM or PM, depending upon the number of criteria met.
Skin findings — Several distinct cutaneous eruptions, which are generally evident at the time of clinical presentation, occur in DM but not in PM . Other skin changes may occur in patients with PM and in patients with DM and are not specific to either disorder. Dermatologic manifestations may be prominent but can be quite subtle in some patients.
Characteristic dermatomyositis findings — Gottron's papules and the heliotrope eruption are the hallmark and likely pathognomonic features of DM. Gottron's sign, photodistributed erythema, poikiloderma, nailfold changes, scalp involvement, and calcinosis cutis are also characteristic and useful in distinguishing DM from PM.
●Gottron's papules – Gottron's papules are erythematous to violaceous papules that occur symmetrically over the extensor (dorsal) aspects of the metacarpophalangeal (MCP) and interphalangeal (IP) joints (picture 1A-C). In addition, these lesions may involve the skin between the MCP and IP joints, particularly when the eruption is prominent. Gottron's papules often have associated scale and may ulcerate. When scaling is present, the lesions may mimic psoriasis or lichen planus.
●Gottron's sign – Definitions used for Gottron's sign have varied in the literature. We define Gottron's sign as the presence of erythematous to violaceous macules, patches, or papules on the extensor surfaces of joints in sites other than the hands, particularly the elbows, knees, or ankles. By contrast, some authors have used the term Gottron's papules to refer to papules in these areas, reserving Gottron's sign for macular or patch-like lesions (picture 2) .
●Heliotrope eruption – The heliotrope eruption is an erythematous to violaceous eruption on the upper eyelids, sometimes accompanied by eyelid edema, which, at times, may be quite marked .
●Facial erythema – Patients may have midfacial erythema that can mimic the malar erythema seen in SLE . In contrast to those with SLE, patients with DM will often have involvement of the nasolabial fold, which can be helpful in distinguishing these two photosensitive midfacial eruptions.
●Photodistributed poikiloderma (including the shawl and V signs) – Poikiloderma refers to skin that demonstrates both hyperpigmentation and hypopigmentation, as well as telangiectasias and epidermal atrophy. In DM, patients may demonstrate poikiloderma in any photo-exposed site; however, classic areas of involvement are the upper back (shawl sign) and the V of the neck and upper chest. The poikiloderma in DM often presents with a violaceous hue. Early in the course of cutaneous disease, these areas may demonstrate only erythema rather than well-developed poikiloderma . The erythema may be macular (nonpalpable) or papular. In rare patients, these lesions become thickened and resemble papular mucinosis. The cutaneous eruption of DM is often associated with significant pruritus, which may assist in distinguishing its photo-exacerbated eruption from that of lupus erythematosus (LE).
●Holster sign – Patients with DM may also have poikiloderma on the lateral aspects of the thighs, referred to as the "Holster sign" . It is unclear why this cutaneous manifestation occurs on this classically photo-protected site.
●Generalized erythroderma – In rare patients, erythroderma may occur, which involves extensive cutaneous surface area, including areas that are less exposed to ultraviolet light.
●Periungual abnormalities – The capillary nail beds in DM may be erythematous and may show vascular changes similar to those observed in other systemic rheumatic diseases (eg, scleroderma and SLE). Abnormal capillary nail bed loops may be evident, with alternating areas of dilatation and dropout and with periungual erythema . In addition, cuticular overgrowth, sometimes termed "ragged cuticles," is characteristic and may be associated with hemorrhagic infarcts within the hypertrophic area . The degree of cuticular involvement is thought to reflect ongoing cutaneous disease activity, representing active vasculopathy .
●Psoriasiform changes in scalp – Changes in the scalp resembling seborrheic dermatitis or psoriasis occur in a high percentage of patients with DM . The scalp involvement in DM is diffuse, often associated with poikilodermatous changes and with prominent scaling. Scalp involvement may result in severe burning, pruritus, and/or sleep disturbance. In addition, severe pruritus may occur in patients without visible disease.
●Calcinosis cutis – The deposition of calcium within the skin, a finding known as calcinosis cutis, occurs commonly in juvenile DM. It is infrequent in adult DM. In children, calcinosis has been associated with a delay in treatment with glucocorticoids and/or immunosuppressive therapy. Calcinosis cutis, which is known to be very challenging to treat, may be seen in a variety of conditions, including SSc, particularly limited cutaneous SSc; SLE (rarely); and overlap connective tissue disorders. It may be more common in patients with DM with the anti-p140/anti-MJ autoantibody
Bhopalwala. H
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
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
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
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
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
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 — 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
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
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
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
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
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
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 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" 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
