Clinical case of giant cell arteritis. Corticosteroid therapy remains the first choice (answer 1 incorrect), to be administered as pulses (doses differ according to the literature, but at least 125 mg/d) in case of ocular involvement (answer 3 incorrect). The current treatment of choice for corticosteroid sparing is Tocilizumab (answer 4 incorrect), which has also been shown to reduce recurrences (answer 2 correct).

Clinical case of giant cell arteritis. Corticosteroid therapy remains the first choice ([HIDDEN]), to be administered as pulses (doses differ according to the literature, but at least 125 mg/d) in case of ocular involvement ([HIDDEN]). The current treatment of choice for corticosteroid sparing is Tocilizumab ([HIDDEN]), which has also been shown to reduce recurrences ([HIDDEN]).

75-year-old male, hypertensive on treatment with enalapril (20 mg/day), who consults for deterioration of general condition, bitemporal headache and mandibular claudication of 3 weeks of evolution. In addition, in the last hours, he refers two episodes of amaurosis fugax of the left eye. Physical examination revealed thickening and absence of pulse in the left temporal artery. Analysis: CRP 6 mg/dl (VN <1); hemoglobin 10.5 g/dl; ESR 92 mm. Chest X-ray normal. Considering the most likely diagnosis, check the correct option regarding treatment:

Rituximab should be administered, since glucocorticoids have been relegated to second-line treatment due to their side effects.

Tocilizumab has been shown to be effective in reducing recurrences and cumulative prednisone dose in more than 50% of patients.

In the presence of ischemic symptoms, and in order not to worsen the vascular risk of the patient, the use of glucocorticoids at doses higher than 30 mg/day should be avoided.

In conjunction with glucocorticoid boluses of 1 g/day, infliximab should be used as a first-line drug for remission induction.

[Ocular complications of giant cell arteritis].

Permanent visual loss (PVL) is the most dreaded complication of giant cell arteritis (GCA). It results from anterior ischemic optic neuropathy or, less commonly, retinal artery occlusion. This complication still occurs in 14 to 20% of patients and is typically devastating and permanent, although it is highly preventable by an early diagnosis of giant cell arteritis and appropriate glucocorticoid treatment. Transient ischemic symptoms such as amaurosis fugax, episodes of blurred vision or diplopia may occur, either heralding visual loss or remaining isolated. In studies, the main predictors of PVL are jaw claudication, amaurosis fugax, lack of systemic "B" symptoms, a modestly increased ESR and a higher haemoglobin level. The evaluation of a GCA patient with PVL includes emergency fundoscopy completed by fluorescein angiography, immediate erythrocyte sedimentation rate, C-reactive protein, and complete blood count. Treatment is extremely urgent mainly because, if left untreated, GCA is associated with visual loss in the fellow eye within days in up to 50% of individuals. Treatment may begin with high-dose intravenous methylprednisolone, followed by oral prednisone administered at 1 mg/kg per day. Daily adjunctive aspirin orally may be added since it has been shown, in retrospective studies, to protect against stroke and visual loss. Although treatment duration of complicated GCA is not codified, an initial PVL deserves close monitoring of patient's systemic symptoms, ESR and CRP to avoid relapses due to a significant risk of late recurrence of visual loss during steroid tapering.

[Non-complicated Horton's disease: initial treatment with methylprednisolone 500 mg/day bolus for three days followed by 20 mg/day prednisone-equivalent. Evaluation of 15 patients].

To assess the efficacy and tolerance of three methylprednisolone boluses (500 mg/d) followed by a standard dose of prednisolone, 20 mg/d, as the initial treatment of non-complicated giant-cell arteritis. A retrospective study of 15 cases. Six men and nine women with a mean age of 70.9 years were treated and followed for 41.5 months. Initial mean ESR was 83 mm; mean C-reactive protein level was 94.6 mg/L. The boluses were well tolerated, excepted in one patient who developed acute psychosis. After initiating the oral treatment, two patients presented signs of clinical relapse during the first month, and were given higher doses of corticosteroids. At 1 month, 12 patients were asymptomatic, nine of whom had normalized ESR and CRP. Mean ESR was 23; mean CRP was 13 mg/L. At 3 months, the mean prednisone dose delivered was 18.2 mg/d. Mean ESR was 12 mm. The cumulative prednisone dose given during the first year was 5,349 (+/- 2,512) mg. In the 13 patients who necessitated no more than 20 mg/d prednisone, no sequelae of giant-cell arteritis, no fractures nor major treatment intolerance occurred-during the first 2 years of treatment. Treatment was stopped in eight patients after a mean duration of 48.6 months. Treatment with pulse methylprednisolone 500 mg/d for 3 days followed by 20 mg/d oral prednisone could be a valuable corticosteroid-sparing strategy in many patients with uncomplicated temporal arteritis.

Polymyalgia rheumatica

Another test that checks the level of C-reactive protein (CRP) in the blood may also be conducted. CRP is produced by the liver in response to an injury or infection, and people with polymyalgia rheumatica usually have high levels. However, like the ESR, this test is also not very specific. Polymyalgia rheumatica is sometimes associated with temporal arteritis, a condition requiring more aggressive therapy. To test for this additional disorder, a biopsy sample may be taken from the temporal artery. Treatment Prednisone is the drug of choice for PMR, and treatment duration is frequently greater than one year. If the patient does not experience dramatic improvement after three days of 10–20 mg oral prednisone per day, the diagnosis should be reconsidered. Sometimes relief of symptoms occurs in only several hours.

IgG4-related disease

Although not validated yet in clinical trials, the common induction regime is prednisolone 30–40 mg per day for 2–4 weeks, then gradually tapered over 3 to 6 months. Recurrences during or after tapering of glucocorticoids are frequent, however. Steroid-sparing immunosuppressive agents might be considered, depending on local availability of these drugs, for use in combination with glucocorticoids from the start of treatment in order to reduce the side-effects of prolonged glucocorticoid usage. Steroid-sparing agents that have been used include rituximab, azathioprine, methotrexate, and cyclophosphamide, although trials are needed to ascertain the effectiveness of each drug in IgG4-RD.

Optic Ischemia -- Treatment / Management

AAION: In cases of high suspicion treatment with high dose corticosteroids should be started immediately after drawing samples for CBC, ESR, CRP without waiting for results of investigations. Immediate treatment prevents vision loss in another eye as there are high chances of involvement of the second eye within days to weeks. Temporal artery biopsy can be delayed for 7 to 10 days if immediate facilities are not available. Pathological changes in the temporal artery will not be affected as they take weeks to months to change. High-dose intravenous methylprednisolone (1 g/day) for 3 to 5 days is preferred. Some studies suggest different duration for intravenous steroid use, a three-day course of high-dose IV steroids, suggesting benefit on visual recovery in the same eye and prevention of disease in the second eye is favored. [11] [12] The consensus approach after intravenous therapy is to start a moderate to a high dose of oral prednisone (1 mg/kg/day). Steroids are slowly tapered over 3 to 12 months, depending on the response. ESR and CRP are followed closely throughout the course.

Pemphigoid

Glucocorticoid sparing drugs For patients who require high dose of corticosteroids for clearing or maintenance, glucocorticoid sparing agents such as immunosuppressive drugs and anti-inflammatory drugs can be used as an adjunct therapy to reduce the systemic side effects of corticosteroids. Patients who have comorbidities and contraindications for corticosteroids may also consider these glucocorticoid sparing agents. Immunosuppressant drug Immunosuppressant drugs include azathioprine (1–3 mg/kg/day in two equally divided doses), mycophenolate mofetil (1000–3000 mg/day or 40 mg/kg/day in two divided doses), and methotrexate (10–15 mg/week).

InternalMed_Harrison

The goals of treatment in giant cell arteritis are to reduce symptoms and, most importantly, to prevent visual loss. The treatment approach for cranial and large-vessel disease in giant cell arteritis is currently the same. Giant cell arteritis and its associated symptoms are exquisitely sensitive to glucocorticoid therapy. Treatment should begin with prednisone, 40–60 mg/d for ∼1 month, followed by a gradual tapering. When ocular signs and symptoms occur, consideration should be given for the use of methylprednisolone 1000 mg daily for 3 days to protect remaining vision. Although the optimal duration of glucocorticoid therapy has not been established, most series have found that patients require treatment for ≥2 years. Symptom recurrence during prednisone tapering develops in 60–85% of patients with giant cell arteritis, requiring a dosage increase. The ESR can serve as a useful indicator of inflammatory disease activity in monitoring and tapering therapy and can be used to judge the

Glucocorticoid

If high doses were used for 11–30 days, cut immediately to twice replacement, and then by 25% every four days. Stop entirely when dose is less than half of replacement. Full adrenal recovery should occur within one to three months of completion of withdrawal. If high doses were used more than 30 days, cut dose immediately to twice replacement, and reduce by 25% each week until replacement is reached. Then change to oral hydrocortisone or cortisone as a single morning dose, and gradually decrease by 2.5 mg each week. When the morning dose is less than replacement, the return of normal basal adrenal function may be documented by checking 0800 cortisol levels prior to the morning dose; stop drugs when 0800 cortisol is 10 μg/dl. Predicting the time to full adrenal recovery after prolonged suppressive exogenous steroids is difficult; some people may take nearly a year. Flare-up of the underlying condition for which steroids are given may require a more gradual taper than outlined above.

Opsoclonus myoclonus syndrome

Some of medication used to treat the symptoms are: ACTH has shown improvements in symptoms but can result in an incomplete recovery with residual deficits. Corticosteroids (such as prednisone or methylprednisolone) used at high dosages (500 mg - 2 g per day intravenously for a course of 3 to 5 days) can accelerate regression of symptoms. Subsequent very gradual tapering with pills generally follows. Most patients require high doses for months to years before tapering. Intravenous Immunoglobulins (IVIg) are often used with varying results. Several other immunosuppressive drugs, such as cyclophosphamide and azathioprine, may be helpful in some cases. Chemotherapy for neuroblastoma may be effective, although data is contradictory and unconvincing at this point in time. Rituximab has been used with encouraging results. Other medications are used to treat symptoms without influencing the nature of the disease (symptomatic treatment):

InternalMed_Harrison

with giant cell arteritis, requiring a dosage increase. The ESR can serve as a useful indicator of inflammatory disease activity in monitoring and tapering therapy and can be used to judge the pace of the tapering schedule. However, minor increases in the ESR can occur as glucocorticoids are being tapered and do not necessarily reflect an exacerbation of arteritis, particularly if the patient remains symptom-free. Under these circumstances, the tapering should continue with caution. Glucocorticoid toxicity occurs in 35–65% of patients and represents an important cause of patient morbidity. Aspirin 81 mg daily has been found to reduce the occurrence of cranial ischemic complications in giant cell arteritis and should be given in addition to glucocorticoids in patients who do not have contraindications. The use of weekly methotrexate as a glucocorticoid-sparing agent has been examined in two randomized placebo-controlled trials that reached conflicting conclusions. Infliximab, a

Giant cell arteritis

GCA is considered a medical emergency due to the potential of irreversible vision loss. Corticosteroids, typically high-dose prednisone (1 mg/kg/day), should be started as soon as the diagnosis is suspected (even before the diagnosis is confirmed by biopsy) to prevent irreversible blindness secondary to ophthalmic artery occlusion. Steroids do not prevent the diagnosis from later being confirmed by biopsy, although certain changes in the histology may be observed towards the end of the first week of treatment and are more difficult to identify after a couple of months. The dose of corticosteroids is generally slowly tapered over 12–18 months. Oral steroids are at least as effective as intravenous steroids, except in the treatment of acute visual loss where intravenous steroids appear to offer significant benefit over oral steroids. Short-term side effects of prednisone are uncommon but can include mood changes, avascular necrosis, and an increased risk of infection. Some of the side

InternalMed_Harrison

Patients with isolated polymyalgia rheumatica respond promptly to prednisone, which can be started at a lower dose of 10–20 mg/d. Similar to giant cell arteritis, the ESR can serve as a useful indicator in monitoring and prednisone reduction. Recurrent polymyalgia symptoms develop in the majority of patients during prednisone tapering. One study of weekly methotrexate found that the use of this drug reduced the prednisone dose on average by only 1 mg and did not decrease prednisone-related side effects. A randomized trial in polymyalgia rheumatica did not find infliximab to lessen relapse or glucocorticoid requirements. Takayasu arteritis is an inflammatory and stenotic disease of medium-and large-sized arteries characterized by a strong predilection for the aortic arch and its branches.

Tocilizumab in giant cell arteritis: Multicenter open-label study of 22 patients.

To assess the efficacy of tocilizumab (TCZ) in giant cell arteritis (GCA) patients with refractory disease and/or with unacceptable side effects due to corticosteroids. A retrospective multicenter open-label study on 22 GCA patients treated with TCZ at standard dose of 8mg/kg/month. The main outcomes were achievement of disease remission and reduction of corticosteroid dose. The mean age ± standard deviation of patients was 69 ± 8 years. The main clinical features at TCZ onset were polymyalgia rheumatica (n = 16), asthenia (n = 7), headache (n =5), constitutional symptoms (n = 4), jaw claudication (n = 2), and visual loss (n = 2). Besides corticosteroids and before TCZ onset, 19 of 22 patients had also received several conventional immunosuppressive and/or biologic drugs. Of 22 patients, 19 achieved rapid and maintained clinical improvement following TCZ therapy. Also, after a median follow-up of 9 (interquartile range: 6-19) months, the C-reactive protein level had fallen from 1.9 (1.2-5.4) to 0.2 (0.1-0.9)mg/dL (p < 0.0001) and the erythrocyte sedimentation rate decreased from 44 (20-81) to 12 (2-20)mm/1st hour (p = 0.001). The median dose of prednisone was also tapered from 18.75 (10-45) to 5 (2.5-10)mg/day (p < 0.0001). However, TCZ had to be discontinued in 3 patients due to severe neutropenia, recurrent pneumonia, and cytomegalovirus infection. Moreover, 1 patient died after the second infusion of TCZ due to a stroke in the setting of an infectious endocarditis. TCZ therapy leads to rapid and maintained improvement in patients with refractory GCA and/or with unacceptable side effects related to corticosteroids. However, the risk of infection should be kept in mind when using this drug in patients with GCA.

Behcet Disease -- Treatment / Management -- Posterior uveitis:

Initial therapy: Combination of oral prednisone and azathioprine Starting dose of prednisone 1 mg/kg per day for one month and tapering as tolerated Methylprednisolone as pulse therapy at a dose of 1 g/day for three days may be used empirically to save the sight. The initial dose of azathioprine is 50 mg daily. As tolerated, increase the daily dose by 50 mg every four weeks. The target dose is 2.5 mg/kg/day. Complete blood count (CBC) is monitored every two weeks initially till the maximum required dose is achieved and then every 6 to 12 weeks. Severe or refractory disease: Infliximab and adalimumab have been used successfully. [45] The initial dose of infliximab is 5 mg/kg at 0, 4, 8, 16, and 24 weeks or 0, 2, 6, and every eight weeks. Adalimumab is given at a loading dose of 80 mg, followed by 40 mg one week later and 40 mg every two weeks thereafter. [46]

Management of giant cell arteritis. Our 27-year clinical study: new light on old controversies.

Giant cell arteritis (GCA) is the prime medical emergency in ophthalmology because of its dreaded complication of visual loss in one or both eyes, which is preventable if these patients are diagnosed early and treated immediately and aggressively with systemic corticosteroids. However, there is much controversy on diagnostic criteria and various aspects of steroid therapy to prevent visual loss. We discuss in detail the reasons for the controversy, clinical criteria to establish a definite early diagnosis of GCA, and its management. To provide new information on corticosteroid therapy in GCA, we also present our 27-year planned study on steroid therapy in GCA in 145 temporal artery biopsy-confirmed GCA patients (96 with and 49 without visual loss) seen and followed for 6 weeks or more in our clinic. The median follow-up time was 2.43 years, with interquartile range of 1-6 years (range 6 weeks to 20.2 years). Intravenous megadose steroid therapy was initially given to 33% followed by oral steroids, while the rest had only the oral therapy. The median starting oral prednisone dose was 80 mg/day, with 40% on >/=100 mg/day. We found that the most reliable and sensitive parameters to regulate and taper down steroid therapy were the levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and NOT systemic symptoms. All patients were maintained at the high-dose prednisone till both the ESR and CRP had stabilized at low levels (that usually took 2-3 weeks), after which very gradual tapering of prednisone was started, guided by the ESR and CRP levels only. The median time to reach the lowest maintenance dose of prednisone at which the ESR and CRP stayed low and stable was 48.7 months (95% CI: 34.6, 71.4 months), and the median lowest prednisone dose achieved was 7 mg/day (interquartile range of 1-16 mg/day). A comparison of patients with and without visual loss showed no significant difference in the time to attain the lowest dose (p = 0.359). Our study showed that no generalization is possible for tapering down of prednisone and there is no set formula because of the infinite variation between individuals. Only 10 (7 without visual loss, 3 with visual loss) of 145 patients were able to stop the therapy and maintain stable ESR and CRP levels. We found that only 4% of GCA patients with visual loss showed any visual improvement with high-dose steroid therapy, and 4% developed further visual loss during the first 5 days of high-dose steroid therapy but none after that. Our studies found no evidence that intravenous megadose steroid therapy was more effective than oral therapy in improving vision or preventing visual deterioration due to GCA.

Neurology_Adams

The administration of prednisone, 45 to 60 mg/d in single or divided doses over a period of several weeks, is indicated in all cases, with gradual reduction to 10 to 20 mg/d and maintenance at this dosage for several months or years, if necessary, to prevent relapse. The headache can be expected to improve within a day or two of beginning treatment; failure to do so brings the diagnosis into question. When the sedimentation rate or CRP is elevated, its return to normal, usually over months, is a reliable index of therapeutic response. Whether symptoms or the blood tests are a better guide to reducing the steroid dose is unclear, one should probably be cautious in lowering the medication if the erythrocyte sedimentation rate (ESR) and CRP remain high. Headaches of Pseudotumor Cerebri (Benign or Idiopathic Intracranial Hypertension, See Chap. 29)

InternalMed_Harrison

mg/kg per day. If new lesions continue to appear after 1–2 weeks of treatment, the dose may need to be increased and/or prednisone may need to be combined with other immunosuppressive agents such as azathioprine (2–2.5 mg/kg per day), mycophenolate mofetil (20–35 mg/kg per day), or cyclophosphamide (1–2 mg/kg per day). Patients with severe, treatment-resistant disease may derive benefit from plasmapheresis (six high-volume exchanges [i.e., 2–3 L per exchange] over ~2 weeks), IV immunoglobulin (IVIg) (2 g/kg over 3–5 days every 6–8 weeks), or rituximab (375 mg/m2 per week × 4, or 1000 mg on days 1 and 15). It is important to bring severe or progressive disease under control quickly in order to lessen the severity and/or duration of this disorder. Accordingly, some have suggested that rituximab and daily glucocorticoids should be used early in PV patients to avert the development of treatment-resistant disease.

[Induction of remission with infliximab in therapy-refractory Wegener's granulomatosis - Follow-up of six patients].

BACKGROUND AND QUESTION: The prognosis of patients with Wegener's granulomatosis (WG) refractory to standard treatment for the induction of remission (cyclophosphamide and steroids) has been poor so far. We report on the results of the follow-up of six patients refractory to the standard regimen (Fauci's scheme) with progressive, imminent visual loss, pulmonary and renal involvement, respectively. How long can remissions be successfully maintained with anti-TNF-alpha-antibody infliximab? What side effects occur? Patients received infliximab (3 mg/kg) in addition to standard therapy with cyclophosphamide and steroids. Intervals between the first two infliximab infusions were 2 weeks, thereafter 4 weeks. Based on the impression of higher efficacy patients received 5 mg/kg infliximab for subsequent infusions. Remission was induced after 4-6 infliximab infusions in five patients. Remission has been maintained in four patients for 16-26 months. After 12 months a pulmonary relapse occurred in one patient, who received azathioprine for the maintenance of remission. Infliximab was stopped in another patient because of a suspected infection. In the light of high cumulative cyclophosphamide doses (100 g/275 g) and cyclophosphamide induced hemorrhagic cystitis, infliximab was added to azathioprine in the two patients with a pulmonary relapse and protrusion of the eye with imminent visual loss, respectively. Remission was induced in both patients. A carcinoid of the bronchus was diagnosed in one patient after 12 months in remission. Infliximab means a new therapeutic option and offers better perspectives for a patient group with previously bad prognosis.

[Principles of acute treatment of Horton's disease. Role of high-dose corticosteroid therapy].

Corticosteroid therapy, the elective treatment for temporal arteritis, can produce adverse effects on bone in this elderly population which usually occur late after acute high-dose administration. Such adverse effects are exceptional and generally have little impact as long as certain cortisone-sparing principles are followed: duration of acute treatments should be as short as possible; dosage can be tapered off rapidly, cutting the acute dose in half in 4 weeks; to titrate dosage, inflammatory proteins should be monitored (especially CRP because of its rapid kinetics and sometimes another protein with slower kinetics); this appears to be more useful for cortisone-sparing than the classical method based on clinical analysis and sedimentation rate; acute regimens should be accompanied by anticoagulation until figrinogen has returned to normal levels; clinical relapses during treatment are usually benign and can generally be controlled by raising the dose slightly; in case of failure due to an acute flare-up far from corticosteroid administration, it would be interesting to study the cortisone sparing effect of giving a 240 mg i.v. bolus of methylprednisolone followed by low-dose corticosteroids; if the relapse is only expressed in laboratory tests, holding the dose at same plateau for two weeks generally leads to spontaneous normalization. Intravenous bolus methlyprednisolone is well tolerated in this population of elderly patients. There is no recognized indication in the uncomplicated forms of temporal arteritis. The cortisone-sparing effect of this technique may result from the fact that the acute oral dose can be reduced. Complicated forms, particularly with ocular involvement, are recognized indications for bolus administration although the administration modalities have not yet been validated. In patients with overt ocular involvement, repeating emergency high-dose i.v. boluses every 6 to 8 hours warrants evaluation with the objective of recovering visual function.

Acute pericarditis

NSAIDs in viral or idiopathic pericarditis. In patients with underlying causes other than viral, the specific etiology should be treated. With idiopathic or viral pericarditis, NSAID is the mainstay treatment. Goal of therapy is to reduce pain and inflammation. The course of the disease may not be affected. The preferred NSAID is ibuprofen because of rare side effects, better effect on coronary flow, and larger dose range. Depending on severity, dosing is between 300–800 mg every 6–8 hours for days or weeks as needed. An alternative protocol is aspirin 800 mg every 6–8 hours. Dose tapering of NSAIDs may be needed. In pericarditis following acute myocardial infarction, NSAIDs other than aspirin should be avoided since they can impair scar formation. As with all NSAID use, GI protection should be engaged. Failure to respond to NSAIDs within one week (indicated by persistence of fever, worsening of condition, new pericardial effusion, or continuing chest pain) likely indicates that a

[Polymyalgia rheumatica and temporal arteritis].

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are closely related and frequently occurring inflammatory diseases with an incidence of 50 and 18 per 100,000 per year, respectively, in people aged 50 years or over. The most frequent symptom of PMR is aching and morning stiffness lasting more than 1 month and exacerbated by movement, occurring in the shoulder and pelvic girdles and in the neck region. GCA is vasculitis of the large and medium-sized arteries that originate from the aortic arch, causing new and marked headache localised over the temporal or occipital areas, jaw claudication, visual impairment or claudication of the arms. GCA is characterised by histopathological panarteritis with a predominantly lymphohistiocytic cell infiltrate. Activation of macrophages is central to the arteritis. Standard treatment for PMR and GCA is glucocorticoids, which may consist of prednisone 10-20 mg/day or its equivalent for PMR patients and prednisone 30-40 mg to 1 mg/kg body weight for GCA patients. For GCA patients with recently impaired vision, treatment should start with high doses of intravenously administered glucocorticoids, such as methylprednisolone 1 g/day for 3 consecutive days. A treatment duration of 1-2 years is often required for patients with PMR or GCA; because of the side effects associated with long-term use of glucocorticoids, osteoporosis prophylaxis with oral calcium supplementation, vitamin D and bisphosphonates is appropriate.

[Relapse of Wegener's granulomatosis. Retrospective study of 18 cases].

During a mean therapeutic follow-up of 4 years, 25 out of 61 patients with Wegener's granulomatosis had one or several relapses. As in 7 of them the initial diagnosis had proved erroneous, this study concerns the remaining 18 patients who together totalled 31 relapses after the correct diagnosis was made. Twenty relapses occurred early on, within 4 months of a change in treatment, and they corresponded to recurrent activity of the disease. Ten relapses occurred later on, after treatment had been discontinued or kept at maintenance dose level. The relapses appeared as early as the first year in 41 percent of the cases. The ENT region was affected in 61 percent of the patients. Nine relapses occurred in the absence of treatment, including 6 which took place 1 to 8 years after treatment. Three relapses occurred less than 3 months after a prednisone and oral cyclophosphamide therapy was initiated. Compared with the group of patients without relapse, those in the relapse group were younger, more often treated with azathioprine and cyclophosphamide administered intravenously, and followed up for a longer period; their probability of survival was also higher. In case of early relapse after withdrawal of treatment the mean duration of that treatment had been shorter than in the absence of relapse. None of the patients whose treatment had been stopped more than 20 months after its onset had an early relapse. These data prompted us to make the following proposals: initially, cyclophosphamide should be administered as bolus injections (the time required to obtain results is then shorter than with the oral route), and maintenance therapy should last at least 20 months. Azathioprine should be used only when cyclophosphamide is contra-indicated. The relative indications for intravenous and oral cyclophosphamide remain to be determined. Discontinuing all treatments is a difficult decision to make, but even then the patients should be under close supervision in view of the possibility of late relapses.

Management of ulcerative colitis

Oral anti-inflammatory drugs require four to six weeks to work. Once remission is induced, maintenance levels can be used: sulfasalazine 2 g/day, mesalamine 1.2-2.4 g/day, or olsalazine 1 g/day. Patients on high dose sulfasalazine require folic supplementation (1 mg/day) because it inhibits folate absorption. If oral Mesalazine is still not working, prednisone is often given, starting at 40–60 mg/day. Prednisone often takes effect within 10–14 days. The dose should then be tapered by about 5 mg/week until it can be stopped altogether.

Prednisone

Withdrawal The magnitude and speed of dose reduction in corticosteroid withdrawal should be determined on a case-by-case basis, taking into consideration the underlying condition being treated, and individual patient factors such as the likelihood of relapse and the duration of corticosteroid treatment. Gradual withdrawal of systemic corticosteroids should be considered in those whose disease is unlikely to relapse and have: received more than 40 mg prednisone (or equivalent) daily for more than 1 week been given repeat doses in the evening received more than 3 weeks of treatment recently received repeated courses (particularly if taken for longer than 3 weeks) taken a short course within 1 year of stopping long-term therapy other possible causes of adrenal suppression

InternalMed_Harrison

Virtually all patients experience a gradual recovery of vision after a single episode of optic neuritis, even without treatment. This rule is so reliable that failure of vision to improve after a first attack of optic neuritis casts doubt on the original diagnosis. Treatment with high-dose IV methylprednisolone (250 mg every 6 h for 3 days) followed by oral prednisone (1 mg/kg per day for 11 days) makes no difference in ultimate acuity 6 months after the attack, but the recovery of visual function occurs more rapidly. Therefore, when visual loss is severe (worse than 20/100), IV followed by PO glucocorticoids are often recommended.

Giant Cell Arteritis (Temporal Arteritis) -- Treatment / Management -- Dosing

Early treatment with a daily divided dose of prednisone 1mg/kg/day or 40 to 60 mg/day (or equivalent) in divided doses is adequate in most cases. This dose shall continue until all the symptoms resolve and acute phase reactants normalize, usually taking 2 to 4 weeks. [24] Subsequently, the dose can be decreased by 10% of the total dose every 2 weeks until the daily dose of 10 mg is reached. Thereafter, tapering shall be by 1mg every month. Alternate-day dosing of corticosteroids is not recommended. Faster tapering of steroids is usually associated with more relapses. Even with the slow tapering, relapses are common and seen in up to 50% of cases and can be associated with recurrence of symptoms and elevation in CRP. The dose of prednisone can be increased by 10mg from the dose during relapse, and once relapse resolves, tapering can resume with careful monitoring.

Neurology_Adams

Most clinicians agree that glucocorticoids (e.g., prednisone, 1 mg/kg, as a single daily dose orally, or intravenously) are a reasonable first therapy for both PM and DM. The response to treatment is monitored by testing of strength and measurement of CK (not by following the erythrocyte sedimentation rate [ESR]). In patients who respond clinically, the serum CK decreases before the weakness subsides; with relapse, the serum CK rises before weakness returns. Once the CK level normalizes and strength improves, typically several weeks or longer, one approach is to reduce the dosage gradually—by no more than 5 mg every 2 weeks—toward 20 mg daily. It is then appropriate to attempt to control the disease with an alternate-day schedule with double this amount (i.e., prednisone, 40 mg every other day) so as to reduce the side effects of the drug. After cautious reduction of prednisone over a period of 6 months to 1 year or longer, the patient can usually be maintained on doses of 7.5 to 20

Macrophage activation syndrome

Hemoglobin <90g/L (in infants <4 weeks: <100g/L) Platelets <100 x 109/L Neutrophils <1.0 x 109/L Fasting triglycerides ≥3.0 mmol/L (i.e., ≥ 265 mg/dl) Fibrinogen ≤1.5 g/L In addition, other specific markers of macrophage activation (e.g. soluble CD163), and lymphocyte activation (e.g. soluble IL-2 receptor) can be helpful. NK cell function analysis may show depressed NK function, or, flow cytometry may show a depressed NK cell population. Treatment The best treatment for MAS has not been firmly established. Most commonly used treatments include high-dose glucocorticoids, and cyclosporine. In refractory cases treatment regimens are used similar to that in HLH. Anakinra may also be effective. See also Cytokine release syndrome References External links Macrophage Activation Syndrome, MedScape Rheumatology Syndromes

[Bolus of methylprednisolone and Horton's disease/rhizomelic pseudo-polyarthritis. Preliminary results of a pilot study of treating the bolus with low doses of corticoids].

The aim of this study was to reduce the side effects of corticosteroid therapy responsible for high morbidity in giant cell arteritis. Nine patients were admitted consecutively for temporal arteritis (7 cases) or polymyalgia rheumatica (2 cases) without ocular involvement (mean age: 69.3 years; positive temporal biopsy: 6 cases). The following protocol was used: methylprednisolone, 500 mg/d, i.v., for 3 consecutive days, then low doses (an average of 22.5 mg/d) of prednisone or an equivalent drug. The mean length of follow-up was 15.1 months (range: 6-22 months). The mean lapse of time until the erythrocyte sedimentation rate returned to normal was 10.6 days (range: 3-30 days). The mean dose of prednisone or an equivalent drug at 6 months was 13 mg/d (range: 5-22.5 mg/d). One patient was cured after 17 months of treatment. Another suffered a biological relapse after 13 months of treatment. All the other patients were asymptomatic with no biological signs of an inflammatory syndrome. The complications included: electrocardiogram modifications without necrosis during pulse therapy in 1 woman; unstable angina developed 2 months after the onset of treatment in 1 man; recurrent urinary infections in 1 predisposed male patient. No bone or metabolic side effects have been noted to date. We think that 3 days of intensive intravenous corticotherapy followed by low doses of corticoïds per os constitute an effective and well-tolerated regimen. Additional studies including comparison with conventional treatments should be carried out to confirm these results and, even better, to evaluate the long-term benefits of this protocol in terms of side effects.

Maprotiline

The use of maprotiline in the treatment of enuresis in pediatric patients has so far not been systematically explored and its use is not recommended. Safety and effectiveness in the pediatric population in general have not been established. Anyone considering the use of maprotiline in a child or adolescent must balance the potential risks with the clinical need. In general, lower dosages are recommended for patients over 60 years of age. Dosages of 50 mg to 75 mg daily are usually satisfactory as maintenance therapy for elderly patients who do not tolerate higher amounts. Available forms Coated Tablets, 10 mg, 25 mg, 50 mg, and 75 mg Injectable concentrate, 25 mg Contraindications Maprotiline may worsen psychotic conditions like schizophrenia and should be given with caution. The antipsychotic treatment should be continued. Patients with bipolar affective disorder should not receive antidepressants whilst in a manic phase, as antidepressants can worsen mania.

[A case in which the subject was affected by Listeia meningoencephalitis during administration of infliximab for steroid-dependent adult onset Still's disease].

The subject was a 22-year-old woman who developed high fever and arthralgias and eruptions in the extremities around June 2005. She sought medical advice at a nearby dermatology clinic, where hepatic dysfunction was noted on blood testing. The patient was thus hospitalized the next day. Although CRP levels were significantly high, no sign of infection was observed and bone marrow cell differentiation was normal. Adult onset Still's disease was diagnosed based on the observation of persistent high fever >39 degrees C, eruptions, increased leukocytes, pharyngeal pain, splenomegaly, hepatic dysfunction, negative autoantibody results from blood testing, and high serum ferritin levels. Administration of prednisolone 30 mg/day was initiated, but proved ineffective. Steroid pulse therapy was conducted, and the subject was transferred to our medical facility for continued treatment. Attempts were made to control the disease using combined steroid and cyclosporine administration; but exacerbation of high serum ferritin levels and hepatic dysfunctions were observed, so a second course of steroid pulse therapy was conducted. Symptoms improved temporarily, but steroid levels were difficult to reduce. Cyclosporine was therefore replaced by methotrexate, and administration of infliximab was initiated. In the course of treatment, administration of a sulfamethoxazole/trimethoprim combination was initiated, but was discontinued due to suspicion of drug-induced hepatic injury. A second administration of infliximab was conducted in late August, and rapid improvements in clinical symptoms and abnormal test values was observed. However, high fever and headache developed suddenly in early September. Based on the results of spinal fluid testing, blood and spinal fluid cultures and MRI of the head, Listeria meningoencephalitis was diagnosed. Diplopia and impaired consciousness occurred during the disease course, and formation of a brain abscess was observed on imaging. However, symptoms were controlled by long-term combination administration of ampicillin and gentamicin. Administration of infliximab was discontinued for treatment of adult onset Still's disease, and steroid levels were reduced following double-membrane filtration plasma exchange. On follow-up, no relapse of symptoms or abnormalities in blood test values were observed, so the subject was discharged from our medical facility in December 2005. In treatment for rheumatic diseases, a dramatic improvement in treatment results for pathologies displaying tolerance against conventional treatments has been acquired with the development of biological drugs. However, opportunistic infections represent a serious problem, and appropriate preventative measures are required. The present report describes a case in which the subject was affected by Listeria meningoencephalitis during administration of infliximab for steroid-dependent adult Still's disease. Since listeriosis is one of the complications, along with tuberculosis, that warrants precautionary measures, this case is reported and discussed.

AGA Clinical Practice Update on the Evaluation and Management of Acute Kidney Injury in Patients With Cirrhosis: Expert Review.

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available published evidence and expert advice regarding the clinical management of patients with suspected acute kidney injury in patients with cirrhosis. This article provides practical advice for the management of patients with cirrhosis and acute kidney injury based on the best available published evidence. This best practice document is not based on a formal systematic review. This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through the standard procedures of Clinical Gastroenterology & Hepatology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Since systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. BEST PRACTICE ADVICE 1: Acute kidney injury (AKI) should be diagnosed when the serum creatinine increases by ≥0.3 mg/dL within 48 hours or is ≥50% from baseline or when the urine output is reduced below 0.5 mL/kg/h for >6 hours. BEST PRACTICE ADVICE 2: Preventive measures against the development of AKI in cirrhosis include (1) avoidance of potentially nephrotoxic medications like nonsteroidal anti-inflammatory drugs (NSAIDs), (2) avoidance of excessive or unmonitored diuretics or nonselective beta-blockade, (3) avoidance of large-volume paracentesis without albumin replacement, and (4) counseling patients to avoid alcohol use. BEST PRACTICE ADVICE 3: (A) Investigation is directed to determining the cause of AKI, which can be due to hypovolemic causes (volume responsive, and the most common cause of AKI in patients with cirrhosis); acute tubular necrosis; hepatorenal syndrome with AKI (HRS-AKI) (a functional renal failure that persists despite volume repletion); HRS with acute kidney disease, a type of functional renal failure of <3 months- duration in which criteria for HRS-AKI are not met; or postrenal, which occurs only rarely. (B) The specific type of AKI should be identified through a careful history, physical examination, blood biochemistry, urine microscopic examination, urine chemistry (Na+ and urea) and selected urinary biomarkers, and renal ultrasound. BEST PRACTICE ADVICE 4: A rigorous search for infection is required in all patients with AKI. A diagnostic paracentesis should be carried out to evaluate for spontaneous bacterial peritonitis; blood and urine cultures and chest radiograph are also required. There is no role for routine prophylactic antibiotics in patients with AKI, but broad-spectrum antibiotics should be started whenever infection is strongly suspected. BEST PRACTICE ADVICE 5: When AKI is diagnosed, diuretics and nonselective beta-blockers should be held, NSAIDs discontinued, the precipitating cause of AKI treated, and fluid losses replaced, administering albumin 1 g/kg/d for 2 days if the serum creatinine shows doubling from baseline. Urine output, vital signs, and when indicated, echocardiography or CVP (if there is a pre-existing central line) should be used to monitor fluid status. BEST PRACTICE ADVICE 6: When the serum creatinine remains higher than twice the baseline value despite these measures, treatment of HRS-AKI should be initiated with albumin at a dose of 1 g/kg intravenously on day 1 followed by 20-40 g daily along with vasoactive agents (terlipressin; if terlipressin is not available, either a combination of octreotide and midodrine; or norepinephrine, depending on institutional preferences) and continued either until 24 hours following the return of the serum creatinine level to within ≤0.3 mg/dL of baseline for 2 consecutive days or for a total of 14 days of therapy. BEST PRACTICE ADVICE 7: Terlipressin should be initiated as a bolus dose of 1 mg every 4-6 hours (total 4-6 mg/d). The dose should be increased to a maximum of 2 mg every 4-6 hours (total 8-12 mg/d) if there is no reduction in serum creatinine at day 3 of therapy by at least 25% compared to the baseline value. Alternatively, clinicians can administer terlipressin by continuous intravenous infusion at a lower starting dose of 2 mg/d, which may reduce ischemic side effects and increase the dose gradually every 24-48 hours up to a maximum dose of 12 mg/d, or reversal of HRS. As per Food and Drug Administration restrictions, terlipressin should not be used in patients with a serum creatinine ≥5 mg/dL, or oxygen saturation of <90%. BEST PRACTICE ADVICE 8: Oral midodrine when used should be initiated at doses of 7.5 mg and titrated upward to 12.5 mg 3 times daily with octreotide (starting with 100 μg and titrating upward to 200 μg subcutaneously 3 times daily). BEST PRACTICE ADVICE 9: Norepinephrine should be used as a continuous intravenous infusion at a starting dose of 0.5 mg/h and the dose increased every 4 hours by 0.5 mg/h to a maximum of 3 mg/h with the goal of increasing the mean arterial pressure by ≥10 mm Hg and/or the urine output to >50 mL/h for at least 4 hours. BEST PRACTICE ADVICE 10: The risks of ischemic side effects of terlipressin and norepinephrine include angina and ischemia of fingers, skin, and intestine. These side effects may be lowered by starting at the lowest dose and gradually titrating upward. BEST PRACTICE ADVICE 11: Fluid status should be closely monitored because of the risk of pulmonary edema with excessive use of albumin. BEST PRACTICE ADVICE 12: Renal replacement therapy (RRT) may be used in the management of (A) AKI secondary to acute tubular necrosis; (B) HRS-AKI in potential candidates for liver transplantation (that is, RRT should not be used in patients with HRS-AKI who are not candidates for liver transplantation); and (C) AKI of uncertain etiology in which the need for RRT may be considered on an individual basis. BEST PRACTICE ADVICE 13: Transjugular intrahepatic portosystemic shunts should not be used as a specific treatment of HRS-AKI. BEST PRACTICE ADVICE 14: Liver transplantation is the most effective treatment for HRS-AKI. Pharmacotherapy for HRS-AKI before proceeding with liver transplantation may be associated with better post-liver transplantation outcomes. Selected patients with HRS-AKI may require simultaneous liver kidney transplantation based on updated Organ Procurement and Transplantation Network listing criteria.


This is an easy clinical case only presenting thrombopenia with clinic, petechiae and epistaxis. 1 is false, there would be fever, hemolysis data, neurological symptoms, in the smear there would be schistocytes. In 2 the coagulation must be altered and in this case it is not mentioned.

This is an easy clinical case only presenting thrombopenia with clinic, petechiae and epistaxis. [HIDDEN], there would be fever, hemolysis data, neurological symptoms, in the smear there would be schistocytes. In [HIDDEN] the coagulation must be altered and in this case it is not mentioned.

An 18-year-old patient who comes to the emergency department with epistaxis of several days' evolution, with no personal or family history of interest. On examination he is afebrile, multiple ecchymoses are observed, no splenomegaly is palpable. Laboratory tests: leukocytes 7.2 x103/μL, Hb 12.3 g/dL, platelets 6.0 x103/μL. Thrombocytopenia is confirmed in the smear, where platelets of increased size are observed. Coagulation and biochemistry studies are normal. What do you consider the most likely diagnosis?

Immune thrombocytopenic purpura

Despite the destruction of platelets by splenic macrophages, the spleen is normally not enlarged. In fact, an enlarged spleen should lead to a search for other possible causes for the thrombocytopenia. Bleeding time is usually prolonged in ITP patients. However, the use of bleeding time in diagnosis is discouraged by the American Society of Hematology practice guidelines and a normal bleeding time does not exclude a platelet disorder. Bone marrow examination may be performed on patients over the age of 60 and those who do not respond to treatment, or when the diagnosis is in doubt. On examination of the marrow, an increase in the production of megakaryocytes may be observed and may help in establishing a diagnosis of ITP. An analysis for anti-platelet antibodies is a matter of clinician's preference, as there is disagreement on whether the 80 percent specificity of this test is sufficient to be clinically useful.

Thrombocytopenia.

Thrombocytopenia is defined as a platelet count of less than 150 × 10(3) per µL. It is often discovered incidentally when obtaining a complete blood count during an office visit. The etiology usually is not obvious, and additional investigation is required. Patients with platelet counts greater than 50 × 10(3) per µL rarely have symptoms. A platelet count from 30 to 50 × 10(3) per µL rarely manifests as purpura. A count from 10 to 30 × 10(3) per µL may cause bleeding with minimal trauma. A platelet count less than 5 × 10(3) per µL may cause spontaneous bleeding and constitutes a hematologic emergency. Patients who present with thrombocytopenia as part of a multisystem disorder usually are ill and require urgent evaluation and treatment. These patients most likely have an acute infection, heparin-induced thrombocytopenia, liver disease, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, disseminated intravascular coagulation, or a hematologic disorder. During pregnancy, preeclampsia and the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome are associated with thrombocytopenia. Patients with isolated thrombocytopenia commonly have drug-induced thrombocytopenia, immune thrombocytopenic purpura, pseudothrombocytopenia, or if pregnant, gestational thrombocytopenia. A history, physical examination, and laboratory studies can differentiate patients who require immediate intervention from those who can be treated in the outpatient setting. Treatment is based on the etiology and, in some cases, treating the secondary cause results in normalization of platelet counts. Consultation with a hematologist should be considered if patients require hospitalization, if there is evidence of systemic disease, or if thrombocytopenia worsens despite initial treatment.

Teetering on a liver's edge: a case report highlighting clinical decision-making in thrombocytopenia.

This report illustrates the importance of a detailed history and physical exam and careful analysis of hematologic parameters when diagnosing ITP. This case demonstrates that even with subtle deviations from typical ITP findings one must promptly reevaluate the diagnosis. This case also highlights the importance of peripheral smear review by an expert in pediatric hematopathology. A previously healthy 10 year-old Asian boy presented with 2 months of easy bruising. Review of systems was negative for any constitutional symptoms. On examination, he appeared well but had numerous large ecchymoses. He had no appreciable lymphadenopathy or splenomegaly. The liver was palpable 1.5 cm below the costal margin. A complete blood count (CBC) showed: platelets = 17 × 109/L, hemoglobin = 128 g/L, white blood cell count = 5.43 × 109/L, and neutrophils = 1.63 × 109/L. A blood smear was reported as normal. Urate was 370 umol/L and lactate dehydrogenase (LDH) was 803 U/L. The child was admitted with a presumptive diagnosis of immune thrombocytopenic purpura (ITP) and treated with intravenous immunoglobulin. The following day, the blood smear was reviewed by a hematopathologist who identified blasts. A bone marrow aspiration (BMA) confirmed the diagnosis of precursor B-cell acute lymphoblastic leukemia. In children presenting with suspected ITP, leukemia should always be considered. A BMA was historically performed on all patients with presumed ITP to rule out leukemia. In 2011, the American Society of Hematology (ASH) stopped recommending routine BMA in patients suspected of having ITP. ASH advises in cases with unusual findings on history, physical examination or CBC, it is reasonable to perform a BMA. Our patient had mild hepatomegaly, which may have qualified him for a BMA. He also had an elevated LDH and urate, which are not listed as criteria for BMA by ASH but were considered atypical for ITP by the clinical team. A literature search did not reveal any primary data assessing these markers. While corticosteroids are a first line treatment in ITP, they must be reserved for when clinicians are confident that the patient does not have leukemia. Steroid administration prior to diagnosing leukemia results in delayed diagnosis and may increase the risk of complications and decrease survival.

Thrombocytopenia

Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in 20% of medical patients and a third of surgical patients. A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. Values outside this range do not necessarily indicate disease. One common definition of thrombocytopenia requiring emergency treatment is a platelet count below 50,000 per microliter. Thrombocytopenia can be contrasted with the conditions associated with an abnormally high level of platelets in the blood: thrombocythemia (when the cause is unknown), and thrombocytosis (when the cause is known). Signs and symptoms

Gestational thrombocytopenia

Diagnosis Gestational thrombocytopenia will become evident during the mid-second trimester through the third trimester of pregnancy and it is diagnosed based on exclusion. For example, women with a history of immune thrombocytopenia or thrombocytopenia, prior to pregnancy, will not be diagnosed with gestational thrombocytopenia. Patients with low platelet counts, lower than 70,000 / μL, will be difficult to diagnose. The reason is because low platelet counts maybe due to gestational thrombocytopenia or immune thrombocytopenia. In such cases, a treatment of immune thrombocytopenia therapy (corticosteroids, or intravenous immunoglobulin) will be instructed. If there is an improvement in the platelet levels, the patient will be diagnosed with immune thrombocytopenia, and if not the patient will be diagnosed with severe gestational thrombocytopenia In order for the physician to determine the underlying cause of the gestational thrombocytopenia, the following tests are conducted -

Thrombocytopenia

Signs and symptoms Thrombocytopenia usually has no symptoms and is picked up on a routine complete blood count. Some individuals with thrombocytopenia may experience external bleeding such as nosebleeds, or bleeding gums. Some women may have heavier or longer periods or breakthrough bleeding. Bruising, particularly purpura in the forearms and petechiae in the feet, legs, and mucous membranes, may be caused by spontaneous bleeding under the skin. Eliciting a full medical history is vital to ensure the low platelet count is not secondary to another disorder. Ensuring that the other blood cell types, such as red blood cells and white blood cells are not also suppressed, is also important. Painless, round, and pinpoint (1 to 3 mm in diameter) petechiae usually appear and fade, and sometimes group to form ecchymoses. Larger than petechiae, ecchymoses are purple, blue, or yellow-green areas of skin that vary in size and shape. They can occur anywhere on the body.

Blood cell

The normal range (99% of population analyzed) for platelets is 150,000 to 450,000 per cubic millimeter. If the number of platelets is too low, excessive bleeding can occur. However, if the number of platelets is too high, blood clots can form thrombosis, which may obstruct blood vessels and result in such events as a stroke, myocardial infarction, pulmonary embolism, or blockage of blood vessels to other parts of the body, such as the extremities of the arms or legs. An abnormality or disease of the platelets is called a thrombocytopathy, which can be either a low number of platelets (thrombocytopenia), a decrease in function of platelets (thrombasthenia), or an increase in the number of platelets (thrombocytosis). There are disorders that reduce the number of platelets, such as heparin-induced thrombocytopenia (HIT) or thrombotic thrombocytopenic purpura (TTP), that typically cause thromboses, or clots, instead of bleeding.

InternalMed_Harrison

The history and physical examination, results of the CBC, and review of the peripheral blood smear are all critical components in the initial evaluation of thrombocytopenic patients (Fig. 140-2). The overall health of the patient and whether he or she is receiving drug treatment will influence the differential diagnosis. A healthy young adult with thrombocytopenia will have a much more limited differential diagnosis than an ill hospitalized patient who is receiving multiple medications. Except in unusual inherited disorders, decreased platelet production usually results from bone marrow disorders that also affect red blood cell (RBC) and/or white blood cell (WBC) production. Because myelodysplasia can present with isolated thrombocytopenia, the bone marrow should be examined in patients presenting with isolated thrombocytopenia who are older than 60 years of age. While inherited thrombocytopenia is rare, any prior platelet counts should be retrieved and a family history regarding

Thrombocytopenia

Immune thrombocytopenic purpura Many cases of immune thrombocytopenic purpura (ITP) also known as idiopathic thrombocytopenic purpura, can be left untreated, and spontaneous remission (especially in children) is not uncommon. However, counts under 50,000 are usually monitored with regular blood tests, and those with counts under 10,000 are usually treated, as the risk of serious spontaneous bleeding is high with such low platelet counts. Any patient experiencing severe bleeding symptoms is also usually treated. The threshold for treating ITP has decreased since the 1990s; hematologists recognize that patients rarely spontaneously bleed with platelet counts greater than 10,000, although exceptions to this observation have been documented.

Idiopathic thrombocytopenic purpura associated with splenic tuberculosis: case report.

Tuberculosis is still one of the most prevalent and fatal infectious diseases in spite of considerable improvements in medical science. Splenic tuberculosis is a rare form of extrapulmonary tuberculosis. There are limited numbers of cases in which immune thrombocytopenia is associated with splenic tuberculosis. We report a case of immune thrombocytopenic purpura due to splenic tuberculosis. Our case was a 58-year-old female with headache, gum bleeding, redness in legs, and ecchymoses on the arms for 10 days. On admission to hospital, laboratory tests were as follows: platelet count 6.000/mmc (150 000-450 000), haemoglobin: 12 g/dl, WBC: 8000/mm3, erythrocyte sedimentation rate: 58 mm/h and C-reactive protein was in normal ranges. After standard laboratory tests, the patient was diagnosed with idiopathic thrombocytopenic purpura. The patient presented abdominal lymphadenopathies and spleen in normal size in radiological examinations. Diagnostic laparotomy and splenectomy and lymph node excision was performed and splenic tuberculosis was detected in pathologic and microbiologic examination. The patient was successfully treated with apheresis platelets suspension, intravenous immunoglobulin and antituberculous therapy. In conclusion, splenic tuberculosis should be suspected in patients who have fever, abdominal lymphadenopathies and immune thrombocytopenic purpura. Histopathological examination is still an ideal method to confirm the diagnosis, suitably aided by microbiological examination.

Schistocyte

Schistocyte count A normal schistocyte count for a healthy individual is <0.5% although usual values are found to be <0.2%. A schistocyte count of >1% is most often found in thrombotic thrombocytopenic purpura, although they are more often seen within the range of 3–10% for this condition. A schistocyte count of <1% but greater than the normal value is suggestive of disseminated intravascular coagulation, but is not an absolute diagnosis. The standard for a schistocyte count is a microscopic examination of a peripheral blood smear.

InternalMed_Harrison

The mortality ranges from 30 to >80% depending on the underlying disease, the severity of the DIC, and the age of the patient. The diagnosis of clinically significant DIC is based on the presence of clinical and/or laboratory abnormalities of coagulation or thrombocytopenia. The laboratory diagnosis of DIC should prompt a search for the underlying disease if it is not already apparent. There is no single test that establishes the diagnosis of DIC. The laboratory investigation should include coagulation tests (aPTT, PT, thrombin time [TT]) and markers of fibrin degradation products (FDPs), in addition to platelet and red cell count and analysis of the blood smear. These tests should be repeated over a period of 6–8 h because an initially mild abnormality can change dramatically in patients with severe DIC.

Thrombocytopenia in Pregnancy -- History and Physical

A physical exam provides clues towards determining the etiology of thrombocytopenia. Patients with gestational thrombocytopenia are often healthy, asymptomatic women who are found to have low platelets on lab investigations. [6] [5] [4] On the contrary, a pregnant woman with TMA is usually a gravely-ill patient often presenting to the emergency room or admitted to high-risk obstetric units. Patients with low platelet count usually present with mucocutaneous bleeding. However, joint bleed or severe bleeding should prompt a workup towards severe coagulopathies like DIC. Physical exam should also evaluate for hepatomegaly and/or splenomegaly (cirrhosis, lymphoproliferative disorders, etc.), skeletal deformities (like absent radius, humeral abnormality and sometimes phocomelia seen in thrombocytopenia absent radii syndrome) and skin exam (like petechiae or purpura seen commonly with ITP, or, eczema seen in Wiskott-Aldrich Syndrome). [7] [29]

Gestational thrombocytopenia

Gestational (incidental) thrombocytopenia is a condition that commonly affects pregnant women. Thrombocytopenia is defined as the drop in platelet count from the normal range of 150,000 –400,000 / μL to a count lower than 150,000 / μL. There is still ongoing research to determine the reason for the lowering of platelet count in women with a normal pregnancy. Some researchers speculate the cause to be dependent on dilution, decreased production of platelets, or an increased turnover event. Although women with normal pregnancy experience a low platelet count, women experiencing a continuous drop in platelet will be diagnosed with thrombocytopenia and women with levels greater than 70,000 / μL will be diagnosed with gestational thrombocytopenia. Thrombocytopenia affects approximately 7-10% of pregnant women and of the 7-10%, within that population; approximately 70-80% have gestational thrombocytopenia

Thrombocytopenic purpura

Thrombocytopenic purpura are purpura associated with a reduction in circulating blood platelets which can result from a variety of causes, such as kaposi sarcoma. Types By tradition, the term idiopathic thrombocytopenic purpura is used when the cause is idiopathic. However, most cases are now considered to be immune-mediated. Another form is thrombotic thrombocytopenic purpura. Diagnosis Diagnosis is done by the help of symptoms and only blood count abnormality is thrombocytopenia. Treatment See also Aspirin Hematopoietic ulcer Thrombocyte References External links Vascular-related cutaneous conditions Coagulopathies

Screening and diagnosis of coagulation disorders.

After clinical assessment, pertinent history, and family history, the clinician often has a good idea concerning the cause of a patient's bleeding. The most appropriate laboratory tests can then be ordered. Routine screening tests include a complete blood cell count, platelet count, and evaluation of a peripheral blood sample, a prothrombin time, and an activated partial thromboplastin time. Thrombocytopenia may result from idiopathic thrombocytopenic purpura, disseminated intravascular coagulation, or, less commonly, acute leukemia, aplastic anemia, thrombotic thrombocytopenic purpura, or a particular drug that a patient is taking. Again, the patient's history, physical findings, and evaluation of a well-prepared peripheral blood smear will be helpful in determining the cause of the patient's thrombocytopenia. An isolated prolongation of the activated partial thromboplastin time may result from low levels of factors VIII, IX, or XI. A slightly prolonged activated partial thromboplastin time and a moderate decrease in factor VIII may reflect von Willebrand disease or the "carrier" state for hemophilia A. In women a greatly prolonged activated partial thromboplastin time and very low levels of factor VIII (< 3%) most often result from an acquired factor VIII inhibitor (autoantibody against factor VIII) or from severe (type III) von Willebrand disease. If von Willebrand disease is suspected (because of menorrhagia with or without other mucous membrane bleeding, a positive family history, and a prolonged activated partial thromboplastin time), more specific laboratory tests for this disease should be done. These include assays of factor VIII, von Willebrand factor antigen, von Willebrand factor activity (measured by the ristocetin cofactor assay), and template bleeding time. In von Willebrand disease the defect is in von Willebrand factor. The affected individual may have subnormal levels of structurally and functionally normal von Willebrand factor (this is called "classic" or type I von Willebrand disease) or may produce von Willebrand factor that is structurally and functionally abnormal (von Willebrand disease type 2). Individuals who inherit a gene for von Willebrand disease from both parents have severe (type 3) von Willebrand disease and will have extremely low levels (< 3%) of von Willebrand factor and factor VIII and will have a very prolonged bleeding time. In most populations type I disease is the most common form, whereas type 3 is the least commonly encountered form. It should be noted that levels of von Willebrand factor can be influenced by the patient's blood type (persons who have blood type AB have 60% to 70% higher levels than do persons who have blood type O) and can be elevated during pregnancy, stress, and hyperthyroidism. The two major functions of von Willebrand factor are to serve as a "bridge" between platelets and injury sites in blood vessel walls and to protect circulating factor VIII from rapid proteolytic degradation. Thus, if a patient has either too little or functionally abnormal von Willebrand factor, the bleeding time will be prolonged and factor VIII will be decreased (because it is not being protected by von Willebrand factor). It should be determined which type of von Willebrand disease a particular patient has because treatment depends on type. Multimeric analysis of von Willebrand factor can be done with use of sodium dodecyl sulfate gels, radiolabeled antibody to von Willebrand's factor, and autoradiography. This will allow visualization of the multimeric structure of von Willebrand factor. In type I disease all bands are present, whereas in the type 2 variants 2A and 2B no high-molecular-weight multimers are seen. Desmopressin acetate (which is available in parenteral form for intravenous use and in a highly concentrated intranasal spray formulation) is the treatment of choice for classic type I disease. The drug effects a rapid release of von Willebrand factor from endothelial cell stor

Thrombocytopenia

Increased destruction Abnormally high rates of platelet destruction may be due to immune or nonimmune conditions, including: Immune thrombocytopenic purpura Thrombotic thrombocytopenic purpura Hemolytic–uremic syndrome Disseminated intravascular coagulation Paroxysmal nocturnal hemoglobinuria Antiphospholipid syndrome Systemic lupus erythematosus Post-transfusion purpura Neonatal alloimmune thrombocytopenia Hypersplenism Dengue fever Gaucher's disease Zika virus Medication-induced These medications can induce thrombocytopenia through direct myelosuppression: Valproic acid Methotrexate Carboplatin Interferon Isotretinoin Panobinostat H2 blockers and proton-pump inhibitors Other causes Lab error, possibly due to the anticoagulant EDTA in CBC specimen tubes; a citrated platelet count is a useful follow-up study Snakebite Niacin toxicity Lyme disease Thrombocytapheresis (also called plateletpheresis) Niemann–Pick disease Diagnosis

Efficient diagnosis of thrombocytopenia.

Thrombocytopenia may be a benign, incidental finding in an asymptomatic patient or the sign of a potentially life-threatening disorder. The history, physical examination and peripheral blood smear can assist the physician in determining the diagnosis and treatment. After the initial blood count is repeated to help eliminate the possibility of laboratory error, a thorough history, complete physical examination, complete blood cell count and appropriate laboratory tests are required. The history may reveal related illnesses, risk factors such as infection or drug use, or a family history suggestive of congenital thrombocytopenia. The physical examination should concentrate on the lymphatic and hepatosplenic systems, with the physician looking for jaundice, fever or petechiae. With the review of a complete blood cell count and a peripheral smear examination, the initial work-up is completed and may prevent additional, unnecessary testing. Etiology-specific tests follow if needed. Serious spontaneous bleeding is usually a risk only in patients with platelet levels under 20,000 per mm3.

Coagulation

Decreased platelet numbers (thrombocytopenia) is due to insufficient production (e.g., myelodysplastic syndrome or other bone marrow disorders), destruction by the immune system (immune thrombocytopenic purpura/ITP), or consumption (e.g., thrombotic thrombocytopenic purpura/TTP, hemolytic-uremic syndrome/HUS, paroxysmal nocturnal hemoglobinuria/PNH, disseminated intravascular coagulation/DIC, heparin-induced thrombocytopenia/HIT). Most consumptive conditions lead to platelet activation, and some are associated with thrombosis. Coagulation factor disorders The best-known coagulation factor disorders are the hemophilias. The three main forms are hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency or "Christmas disease") and hemophilia C (factor XI deficiency, mild bleeding tendency).

Thrombocytopenia -- History and Physical

History. Obtaining a thorough history helps to identify the etiology of thrombocytopenia. Patients with platelets greater than 50000/mL, rarely have symptoms. Patients with platelets under 20000/mL most likely have spontaneous bleeding.

Lemierre's syndrome

Production of bacterial toxins such as lipopolysaccharide leads to secretion of cytokines by white blood cells which then both lead to symptoms of sepsis. F. necrophorum produces hemagglutinin which causes platelet aggregation that can lead to diffuse intravascular coagulation and thrombocytopenia. Diagnosis Diagnosis and the imaging (and laboratory) studies to be ordered largely depend on the patient history, signs and symptoms. If a persistent sore throat with signs of sepsis are found, physicians are cautioned to screen for Lemierre's syndrome. Laboratory investigations reveal signs of a bacterial infection with elevated C-reactive protein, erythrocyte sedimentation rate and white blood cells (notably neutrophils). Platelet count can be low or high. Liver and kidney function tests are often abnormal.

Platelet

Disorders Adapted from: The three broad categories of platelet disorders are "not enough"; "dysfunctional"; and "too many". Thrombocytopenia Immune thrombocytopenias (ITP) – formerly known as immune thrombocytopenic purpura and idiopathic thrombocytopenic purpura Splenomegaly Gaucher's disease Familial thrombocytopenia Chemotherapy Babesiosis Dengue fever Onyalai Thrombotic thrombocytopenic purpura HELLP syndrome Hemolytic–uremic syndrome Drug-induced thrombocytopenic purpura (five known drugs – most problematic is heparin-induced thrombocytopenia (HIT) Pregnancy-associated Neonatal alloimmune associated Aplastic anemia Transfusion-associated Pseudothrombocytopenia idiopathic thrombocytopenic purpura Vaccine induced immune thrombocytopenia Gilbert's syndrome

Check for a family history of thrombocytopenia or bleeding disorders.

Neonatal alloimmune thrombocytopenia

Related conditions Immune thrombocytopenic purpura (), sometimes called idiopathic thrombocytopenic purpura is a condition in which autoantibodies are directed against a patient's own platelets, causing platelet destruction and thrombocytopenia. Anti-platelet autoantibodies in a pregnant woman with immune thrombocytopenic purpura will attack the patient's own platelets and will also cross the placenta and react against fetal platelets. Therefore, is a significant cause of fetal and neonatal immune thrombocytopenia. Approximately 10% of newborns affected by will have platelet counts <50,000 μL−1 and 1% to 2% will have a risk of intracerebral hemorrhage comparable to infants with .

[The analysis of national examination for the license of medical practice in Japan (reference to the hematological clinical laboratory data)].

It seems to us an important task to analyze the problems appeared in the national examinations of the license of medical practice in respect of clinical laboratory data. The national examination of medical license in Japan begun from 1946, about 45 years ago. In those days, clinical examination is not so developed, a pastoral era, so clinical pathology was not clearly distinguished from internal medicine. Recently it is widely emphasized that national examination for the practical medical practice should be focused on the primary care medicine, so on, which has evidently influenced the appearance rate and number of miscellaneous kinds of clinical laboratory data in the examination problems. On the other hand, We have studied the tendency and mode of appearance of clinical laboratory data in the question of above mentioned examination for several years, in general, and especially in the areas of hematology. The cardinal questions of hematological field were blood cell count (RBC, hematocrit, hemoglobin, WBC, white cell differential, PLATELET), blood sedimentation rate, coagulation and fibrinolysis factor, bone marrow findings in miscellaneous diseases, classification and staging of malignant lymphomas, so on. In conclusion, the rate of appearance and significance of clinical laboratory data in the examination mentioned is more and more increased. However, comprehensive education of clinical pathology now is improved but not accomplished, which reflects tendency and styles of the problems of the examination. So more efforts will be needed to those who continuously study clinical pathology and educate them to the medical students.

Plateletpheresis

Platelet transfusion Platelet transfusions are traditionally given to those undergoing chemotherapy for leukemia, multiple myeloma, those with aplastic anemia, AIDS, hypersplenism, idiopathic thrombocytopenic purpura (ITP), sepsis, bone marrow transplant, radiation treatment, organ transplant or surgeries such as cardiopulmonary bypass. Platelet transfusions should be avoided in those with thrombotic thrombocytopenic purpura (TTP) because it can worsen neurologic symptoms and acute renal failure, presumably due to creation of new thrombi as the platelets are consumed. It should also be avoided in those with heparin-induced thrombocytopenia (HIT) or disseminated intravascular coagulation (DIC). In adults, platelets are recommended in those who have levels less than 10,000/µL, or less than 20,000/µL if a central venous catheter is being placed, or less than 50,000/µL if a lumbar puncture or major surgery is required. Whole blood platelets

Disseminated Intravascular Coagulation -- Evaluation

No single history, physical exam, or laboratory component can lead to a diagnosis of or rule out DIC; therefore, a combination of both subjective, objective, and laboratory findings should be utilized to make a diagnosis of DIC. Laboratory findings suggestive of DIC include both an increased prothrombin time (PT) and an increased partial thromboplastin time (PTT), as well as a decreased fibrinogen level as widespread activation and consumption of the clotting cascade occurs. The overall platelet count and hematocrit level may be reduced as well. Schistocytes or fragmented erythrocytes are also commonly seen on a peripheral blood smear. The presence of fibrin split products additionally has a high sensitivity but low specificity for the presence of DIC. A specific scoring system to assess for the presence of DIC was established in 2007. This score includes platelet count, fibrin markers such as D-dimer, prolonged PT, and fibrinogen level, with a score over five indicating a high likelihood for overt DIC. [18] [19] [20] [21]

Neonatal alloimmune thrombocytopenia

Mothers with thrombocytopenia or a previous diagnosis of should be tested for serum anti-platelet antibodies. A woman with symptomatic thrombocytopenia and an identifiable anti-platelet antibody should be started on therapy for their which may include steroids or . Fetal blood analysis to determine the platelet count is not generally performed as -induced thrombocytopenia in the fetus is generally less severe than . Platelet transfusions may be performed in newborns, depending on the degree of thrombocytopenia. Other conditions causing a low platelet count Other conditions that can cause a low platelet count in the neonate include bacterial and viral infection, disseminated intravascular coagulation and other rare congenital conditions associated with a low platelet count.

[The diagnosis of ITP].

Idiopathic thrombocytopenic purpura(ITP) is a hematologic disorder which causes thrombocytopenia. The diagnosis of ITP is based on the history, physical examination and, complete blood count, and examination of the peripheral smear. The diagnostic criteria of ITP established by the Ministry of Health, Welfare, and Labor in Japan requires the bone marrow examination and the measurement of platelet associated IgG, but those tests are not always necessary according to the guidelines developed by the American Society of Hematology. The appropriate strategies for the diagnosis of ITP need to be established. In this paper, some new examinations which may help the diagnosis of ITP are also demonstrated.

Gestational thrombocytopenia

Women who have platelet levels lower than 70,000 / μL, during pregnancy, maybe experiencing severe gestational thrombocytopenia or immune thrombocytopenia. In such cases, if the treatment of immune thrombocytopenia therapy (corticosteroids, or intravenous immunoglobulin) does not improve the platelet count, the patient will be diagnosed with severe gestational thrombocytopenia. Severe gestational thrombocytopenia may pose a risk for complications with the use of epidural or general anesthesia during delivery. Prognosis Those who have no previous history of thrombocytopenia, besides the occurrence in previous pregnancies (gestational thrombocytopenia), the platelet levels will go back to a normal range 1–2 months after the delivery. Post delivery, approximately 1–3 months later, women with gestational thrombocytopenia should have a complete blood test conducted. Lastly, gestational thrombocytopenia is a disorder that may reoccur in future pregnancies

Essential thrombocythemia at diagnosis: causes of diagnostic evaluation and presence of positive diagnostic findings.

The reasons for diagnostic evaluation and the clinical and laboratory data at diagnosis of 170 patients with essential thrombocythemia (ET) were studied retrospectively. The age distribution was 19-88 years (median 52 years), and 52 patients were under the age of 45 years. In 111 patients (65%) thrombocytosis was a chance finding, but the past history of 37 of these patients revealed symptoms known to be related to ET. The diagnosis was based on a chance finding in a significantly higher proportion of female (74%) than male (53%) patients. The diagnosis of ET is based mostly on negative findings, i.e., on the exclusion of other causes of thrombocytosis, and positive diagnostic tests would be useful. We evaluated the presence of positive diagnostic findings of myeloproliferative disorders in ET. Splenomegaly was seen in 26% and an abnormal karyotype in 5% of the patients. Abnormal megakaryocyte morphology was seen in 80%, abnormal in vitro growth of hematopoietic progenitors in 74%, and abnormal platelet function in 83% of the patients. Both in vitro cultures of hematopoietic progenitors and platelet functions were studied in 36 patients, and in only two of these were both tests normal. We conclude that in most patients with ET the diagnosis can be strongly supported by positive findings, especially by in vitro cultures of hematopoietic progenitors and studies of platelet function.

[Idiopathic thrombocytopenic purpura in children].

Idiopathic (immune) thrombocytopenic purpura (ITP) is the most frequent hemorrhagic disease in children. It represents the acquired megakaryocytic thrombocytopenia with the shortened life of platelets because of immunologic damage (antibodies absorbed by platelets). In the case of this acquired hemorrhagic disorder, in spite of compensatory increased function of the bone marrow, there is a reduced number of platelets because of their increased destruction by the reticuloendothelial system (destructive thrombocytopenia). There are three forms of ITP: acute, chronic and intermittent. The acute form occurs in 80-90% of cases with bleeding episodes lasting a few days or weeks, but no longer than 6 months. The chronic form occurs in 10-15% of children, while the rarest-intermittent form is characterized by periods of normalization in regard to the number of platelets but also with relapse in intervals of 1-3 months. The disease is caused by an immunological disorder in the sense of an imbalanced immune response. Immunologic damages of platelets cause shortening of the opsonized platelets life span. The most frequent platelet opsonins are the immumoglobulin G (IgG) antibodies directed at the platelet membrane in the form of autoantibodies, alloantibodies or possibly absorbed antigen caused by microorganism infection or drug intake. It is typical for the phenomenon of bleeding that it starts suddenly and without any other sign of illness. The most frequent acute form appears between the second and fourth year, and is characterized by seasonal occurrence usually after acute viral infections. Children older than 10 years of age, like adults, often have the chronic form associated with other immunologic disorders. The disease affects girls more often than boys (about three times more often) with moderate and constant increase of antiplatelet antibodies. Hemorrhagic manifestations include: petechiae, purpura, epistaxis, gastrointestinal and genitourinary bleeding. They depend on the grade of thrombocytopenia, although there is no strict correlation between the number of platelets and volume of bleeding. Low mortality of the acute ITP is almost exclusively due to intracranial hemorrhage. LABORATORY STUDIES: Thrombocytopenia represents a decrease in the number of blood platelets being a basic abnormality of the blood count. The half-life of platelets in ITP is shortened. Detection of antiplatelet antibodies is connected with technical difficulties, so they are established in about 30% of cases. Bleeding time is prolonged and so is the coagulum retraction which may be completely missed. The Rumpel-Leede test is positive. Clinical differentiation of drug-induced thrombocytopenia is not possible. However, other differential diagnostic possibilities are thrombotic-thrombocytopenic purpura and hemolytic-uremic syndrome. A child with aplastic anemia or acute leukemia, beside thrombocytopenia, has a characteristic finding of white and red blood cell count. Thrombocytopenia with absent radii syndrome is associated with skeletal system abnormalities. New knowledge about the role of the immune system in ITP determines the modern therapeutic modalities. In cases of acute ITP in children, there are two therapeutic options or therapies of choice: corticosteroids and high doses of intravenous immunoglobulin. Immunosupressive therapy means anti Rh(D) immunoglobulin, cyclosporine, cytostatics, danazol, loaded platelets. In cases of distinctive hemorrhagic syndrome there are also indications for platelet transfusion. Nowadays splenectomy is more restricted, because one third of cases is unsuccessful, whereas plasmapheresis is rarely used in children because of possible complications. ITP is the most frequent hemorrhagic disease in children. The disease is basically caused by an immunologic disorder with platelet destruction due to increased immunoglobulin on their membrane. (ABSTRACT TRUNCATED)