Children With Lupus Essay
Children With Lupus Essay
Researchers analyzed data reports children with lupus kidney disease had more than twice (2.4 times) the risk of dying compared to children with other forms of kidney disease (para.5). Kidney failure or disease caused by lupus is called Lupus nephritis. This has become a major concern of various medical institute especially lupus related organizations. Last April 14, 2011, the Lupus Foundation of America (LFA) with coordination of RN.com, RxSchool.com, and Dr. Mary Anne Dooley, Member, LFA’s Medical-Scientific Advisory Council, launched a new continuing education program for the nurses, pharmacists, and pharmacy technicians. The program entitled ‘Lupus, Deciphering the Clues’ will enhance health professionals awareness of lupus diagnosis and treatments, to meet the needs of early diagnosis and treatment to avoid further vital organ complications. It has been observed by the LFA, based on their own survey, more than fifty percent among lupus patient had visited three or more doctors, and some even suffered four or more years, before they were being diagnosed (Medical News Today, 2011).Children With Lupus Essay. May this program will be of great help to minimize lethal cases of Lupus nephritis to children, as well as to adults. Actually, researchers have been very enthusiastic in performing in-depth study to learn more about lupus and how lupus nephritis developed. LFA(2011) related the experimentation performed on nineteen week-old female mice to learn about the role of immune system proteins called interferons (IFNs) and macrophages (white blood cells) in the development of lupus nephritis. The mice were divided into three groups, wherein mice in the first group were injected three times per week for four weeks of a drug called polycytidylic acid (PCA) which will cause increased activity of IFNs that will start out lupus. The mice in the second group were injected a single dose only of one kind of lupus-related IFN called type I IFN, while the mice in the third group were injected with salt water only, to be used as comparison group. The mice urine were monitored for protein development testing. Then after two weeks, the first and second group of mice manifested developed protein in urine, evidence of developed lupus nephritis. Animal experimentation served as an instrument to discern what types of imbalances might be causing human lupus, and may contribute in finding ways for treatment. Yet, the researchers admitted that such animal experimentations have limitations since there are many known, as well as unknown, differences between human and mice immune system.Children With Lupus Essay. But still, this may shed light for further studies on what treatment might or might not be useful for treating lupus. As expected, urine protein testing would become useful in early detection of kidney damage from lupus. Therefore, Medical News Today (2010) reported a newly discovered simple urine tests for four proteins that might serve as an instrument for early detection of kidney disease in patient with lupus. Likewise, as the article reports, the UT Southwestern Medical Center researchers conducted experiments on mice and found out four proteins protease, PGDS, SAP and SOS showed up in larger amounts on mice urine with progressive kidney damage. They believed that each of these proteins has corresponds in human’s protein or either present in human system. Researchers admitted that this kind of tests might take years to be utilized clinically since they are
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that can involve any organ system with a wide range of disease manifestations, and can lead to significant morbidity and even mortality. This article reviews the epidemiology, common clinical features, complications of disease, and briefly discusses the available treatment options. In addition, important medical and psychosocial issues relevant to the pediatrician caring for children and adolescents with SLE are discussed.Children With Lupus Essay.
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that can involve any organ system, and may lead to significant morbidity and even mortality. In this article we review the epidemiology, common clinical features, complications of disease, and briefly address available treatment options. Further, we discuss important medical and psychosocial issues relevant to the pediatrician caring for children and adolescents with SLE.
Epidemiology
Childhood-onset SLE (cSLE) is a rare disease with an incidence of 0.3-0.9 per 100.000 children-years and a prevalence of 3.3-8.8 per 100.000 children.1 A higher frequency of cSLE is reported in Asians, African American, Hispanics and native Americans.2,3When compared to two more common childhood autoimmune diseases, Juvenile Idiopathic Arthritis (JIA) and type 1 Diabetes, cSLE is around 10 to 15 times less common in white children.4,5 However, in Asian children, cSLE is reported to be equally as common as JIA.6 Most studies report a median age of onset of cSLE between 11-12 years; the disease is quite rare under the age of 5 years. Children With Lupus Essay. As in adult onset SLE, approximately 80% of patients with cSLE are female.7,8
Classification and Diagnosis of cSLE
SLE is called the great mimicker, as the disease shares characteristics with many other (autoimmune) diseases. Especially when the classic malar rash is absent, diagnosing SLE can be a challenge. However, the astute pediatrician who considers SLE when presented with an unusual constellation of symptoms can recognize important patterns of disease manifestations crucial for the diagnosis. Most patients who are diagnosed with cSLE fulfill 4 or more of the American College of Rheumatology classification criteria for SLE (Table 1).9,10 The criteria were designed for use in research studies, and we caution that the diagnosis of SLE should not solely be based on fulfilling these criteria. Although not rigorously studied in cSLE, the criteria have a greater than 95% sensitivity and specificity for the diagnosis of cSLE.11
Table 1
| Criterion | Definition |
|---|---|
| 1. Malar rash | Flat or raised erythema over the malar eminences, spares the nasolabial folds |
| 2. Discoid rash | Erythematosus raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur |
| 3. Photosensitivity | Skin rash following sunlight exposure, by history or physician observation |
| 4. Oral ulcers | Oral or nasopharyngeal ulceration, usually painless |
| 5. Arthritis | Nonerosive arthritis involving two or more peripheral joints, characterized by tenderness, swelling, or effusion |
| 6. Serositis | Pleuritis—convincing history of pleuritic pain or rub on auscultation or evidence of pleural effusion or Pericarditis—documented by electrocardiogram, echocardiogram or rub |
| 7. Renal disorder | Persistent proteinuria greater than 0.5 g/d or Cellular casts—may be red cell, hemoglobin, granular, tubular, or mixed |
| 8. Neurological disorder |
Seizures in the absence of offending drugs or metabolic derangements or Psychosis in the absence of offending drugs or metabolic derangements |
| 9. Hematological disorder |
Hemolytic anemia with reticulocytosis or Leukopenia less than 4000/mm3 on two or more occasions, or Lymphopenia less than 1500/mm3 on two or more occasions, or Thrombocytopenia less than 100,000/mm3 |
| 10. Immunological disorder |
Antibody to native DNA, or Antibody to Sm protein, or Antiphospholipid antibodies – either anticardiolipin antibodies, presence of the lupus anticoagulant, or false positive serological test for syphilis |
| 11. Antinuclear antibody |
Presence of antinuclear antibody by immunofluorescence or an equivalent assay. Children With Lupus Essay. |
Adapted from Tan EM, Cohen AS, Fries JF et al: The 1982 revised criteria for the classification of systemic lupus erythematosus, Arthritis Rheum 25:1271-1277, 1982; and Hochberg MC: Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus, Arthritis Rheum 40:1725, 1997.
Clinical Features
The current review will not attempt to describe all possible clinical manifestations but instead we focus on specific features that may be crucial for immediate recognition. Table 2 summarizes the frequencies of the common manifestations of cSLE.7,12-17 SLE can affect any organ system, and leads to glomerulonephritis and central nervous system involvement arguably more often in cSLE than in adults with SLE.
Table 2
| Clinical Feature | Prevalence of Involvement |
|---|---|
| Constitutional and generalized symptoms | |
| Fever | 37 – 100% |
| Lymphadenopathy | 13 – 45% |
| Weight loss | 21 – 32% |
| Mucocutaneous | 60 – 90% |
| Musculoskeletal | 60 – 90% |
| Nephritis | 48 – 78% |
| Neuropsychiatric disease (NPSLE) | 15 – 95% |
| Gastrointestinal | 24 – 40% |
| Hematologic | 50 – 100% |
| Cardiovascular | 25 – 60% |
| Pulmonary | 18 – 81% |
Data from 7, 12, 17,13,14-16
Constitutional Symptoms
Patients ultimately diagnosed with cSLE frequently recount nonspecific constitutional symptoms that include fever, fatigue, anorexia, weight loss, alopecia and arthralgias.7,12These and other symptoms of diffuse generalized inflammation including lymphadenopathy and hepatosplenomegaly occur both at onset and during disease flares.
Mucocutaneous
The hallmark of SLE is the malar, or butterfly rash. The rash is seen in 60 – 85% of children with SLE, is generally described as erythematous, raised, non-pruritic, and non-scarring. The rash often extends over the nasal bridge, affects the chin and ears, but spares the nasolabial folds (Figure 1). Children With Lupus Essay. It is photosensitive in more than a third of patients, and exacerbation of the photosensitive rash frequently heralds the onset of a systemic flare. Therefore, sunscreen with a high sun protection factor, as well as hats and protective clothing are recommended year round for all individuals with SLE.
Malar Rash of cSLE
Discoid rash, unlike in adult-onset SLE, is a rare manifestation of cSLE, occurring in fewer than 10% of patients.7 This scarring rash most frequently occurs on the forehead and scalp, and its scaly appearance may be mistaken as a tinea lesion.18 Table 3summarizes the spectrum of dermatologic involvement, illustrating the diverse range of skin manifestations. Children and adolescents with SLE can develop a rash of (almost) any morphology, location and distribution, often presenting a diagnostic challenge to the primary care physician. A skin biopsy for histology aids in making the correct diagnosis, although biopsies of facial skin should be avoided. Non-scarring hair loss is common, but not specific for SLE. The alopecia is most often noted as thinning of the temporal areas of the scalp, although rarely it is more global and severe enough to require systemic immunosuppressive therapy. Nevertheless, for the affected child or adolescent, even mild hair loss can be distressing. Children With Lupus Essay.
Table 3
| Rash |
| Malar (“butterfly”) rash |
| Annular erythema |
| Discoid lupus erythematosus |
| Maculopapular and/or linear (nonspecific) rash |
| Bullous lupus (rare) |
| Photosensitivity |
| Alopecia |
| Raynaud’s phenomenon |
| Palmar/plantar/periungual erythema |
| Livedo reticularis |
| Vasculitis |
| Petechiae |
| Palpable purpura (leukocytoclastic vasculitis) |
| Chilblains/Nodules |
| Digital ulcers |
Involvement of the oral and nasal mucosa ranges from oral and/or nasal hyperemia to painless oral ulcers of the hard palate (Figure 2) and shallow nasal septal ulcers, and rarely, nasal septal perforation. Due to both the location and painless nature of these lesions, the practitioner may overlook these findings if the degree of suspicion for SLE is low.Musculoskeletal
The range of musculoskeletal involvement includes features that occur as a consequence of active SLE, and those that are secondary to treatment and/or chronic illness. Manifestations include arthralgias and arthritis, avascular necrosis, bone fragility fractures and secondary pain amplification. Arthritis occurs in 80% of patients with cSLE, and although the typical description is that of a painful polyarthritis, in practice a significant proportion of children with SLE experience minimal pain. The arthritis is identical in many ways to JIA, with effusions and decreased range of motion of both small and large joints and significant morning stiffness, however; the arthritis is almost always non-erosive and non-deforming. Arthralgias also commonly occur, and can be secondary to a pain amplification syndrome that occurs during or following a disease flare with resultant poor sleep and daytime fatigue, decreased cardiovascular conditioning and generalized pain.
Avascular necrosis can occur in patients treated with corticosteroids, and may be idiosyncratic to the dose of medication, although occurs more frequently in patients with SLE than with other diseases that are similarly treated with corticosteroids. In addition, osteoporosis is frequent, related to corticosteroid use and associated with an increased fracture risk. Children With Lupus Essay.
Renal disease
Renal involvement occurs in 50 to 75% of all cSLE patients, and more than 90% of those who will develop renal disease will do so within the first 2 years after diagnosis.7Initial manifestations of renal disease range from minimal proteinuria and microscopic hematuria to nephrotic-range proteinuria, urinary casts, severe hypertension, peripheral edema, and renal insufficiency or acute renal failure. SLE most commonly affects the glomerulus (i.e. “lupus nephritis”), and the renal interstitium is rarely involved. In a patient with acute renal failure, thrombotic thrombocytopenic purpura (TTP), a thrombotic microangiopathy should be considered. TTP is discussed further below. As the severity of the nephritis often does not correlate with the severity of the clinical signs and symptoms, a renal biopsy should be performed for any suspicion of glomerulonephritis, including persistent mild proteinuria. Histologic diagnosis using a standardized classification (Table 4) guides treatment and aids in determining overall prognosis.
Table 4
| Lupus Nephritis Class |
Description | Histology |
|---|---|---|
| Class I | Minimal mesangial lupus nephritis |
Normal glomeruli by light microscopy, but mesangial immune deposits by immunofluorescence. |
| Class II | Mesangial proliferative lupus nephritis |
Mesangial hypercellularity or mesangial matrix expansion by light microscopy, with mesangial immune deposits by immunofluorescence. |
| Class III | Focal lupus nephritis | Active or chronic focal, segmental, or global glomerulonephritis involving <50% of all glomeruli with diffuse subendothelial immune deposits. |
| Class IV | Diffuse lupus nephritis | Active or chronic diffuse, segmental, or global glomerulonephritis involving >50% of all glomeruli with diffuse subendothelial immune deposits. |
| Class V | Membranous lupus nephritis | Global or segmental subepithelial immune deposits by immunofluorescence or electron microscopy. |
| Class VI | Advanced sclerosing lupus nephritis |
≥ 90% glomeruli globally sclerosed without residual activity. |
Adapted from Weening J.J., D’Agati V.D., Schwartz M.M., et al: The classification of glomerulonephritis in systemic lupus erythematosus revisited. J. Am. Soc. Nephrol. 2004; 15:241-250.
The classification of glomerulonephritis in SLE ranges from Class I (minimal mesangial) to Class VI (advanced sclerosing lupus nephritis), and contain descriptions of the mesangial involvement, degree of renal involvement (focal versus diffuse), and degree of involvement of the affected glomeruli (segmental versus global). In general, Class I (minimal mesangial) and Class II (mesangial proliferative) nephritis are mild lesions, and often require little to no immunosuppressive treatment as their natural history is favorable.Children With Lupus Essay. Class III (focal proliferative) and Class IV (diffuse proliferative) lesions are the most frequent and severe lesions, with more than 80% of cSLE biopsies done at Hospital for Sick Children demonstrating one of these lesions.7 Patients with these proliferative lesions have the highest risk of end stage renal disease (ESRD), and thus are treated with aggressive immunosuppression in attempts to avert this outcome. In contrast, Class V (membranous lupus nephritis), when it occurs as the exclusive lesion, rarely leads to ESRD, therefore, it is generally not treated with the same degree of immunosuppression as Class III or IV. However, Class V lesions are frequently observed in conjunction with other lesions (usually Class III or IV), and in this case the presence of the proliferative lesion directs therapy. Any patient with SLE should have regular measurements of blood pressure, serum creatinine, and urinalysis for proteinuria, hematuria and evidence of urinary casts.
With the use of an aggressive treatment regimen, the incidence of ESRD is lower than in past decades, but still remains between 10 – 20% by 10 years from diagnosis.19,20Patients who develop ESRD require dialysis and can undergo renal transplant when a donor organ is available providing their disease is stable at the time of transplant. While a recent study noted that a third of cSLE patients with ESRD received a transplant within 5 years, another 22% died in that same time period.21 Moreover, there is a risk of recurrence of nephritis in the graft kidney.22 Overall, renal disease remains a significant cause of morbidity and mortality, with the possibility of disease flares even after years of remission. Children With Lupus Essay.
Neuropsychiatric Involvement
SLE can involve both the central and peripheral nervous systems, with 19 distinct neuropsychiatric lupus (NPSLE) syndromes described (Table 5).23 Up to 65% of cSLE patients develop NPSLE at any time during the disease course, and up to 85% of these patients will develop NPSLE within the first 2 years from diagnosis.13,24 As many of the syndromes are infrequent, only the commonest are briefly outlined here.
Table 5
| CENTRAL NERVOUS SYSTEM | PERIPHERAL NERVOUS SYSTEM |
|---|---|
| Aseptic meningitis | Acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barre syndrome) |
| Cerebrovascular disease | |
| Demyelinating syndrome | |
| Headache | Autonomic disorder |
| Movement disorder (chorea) | Mononeuropathy, single/multiplex |
| Myelopathy | Myasthenia gravis |
| Seizure disorder | Neuropathy, cranial |
| Acute confusional state | Plexopathy |
| Anxiety disorder | Polyneuropathy |
| Cognitive dysfunction | |
| Mood disorder | |
| Psychosis |
Adapted from American College of Rheumatology : Nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum. 1999; 42:599-608.
Headache
Symptoms ranging from mild intermittent tension-type headaches, to daily, debilitating severe headaches that require prescription pain medication occur in 50 – 95% of patients.13,25 Headache on its own can be a manifestation of active SLE, an indication of increased intracranial pressure, or of intracranial pathology such as sinus vein thrombosis especially in patients with antiphospholipid antibodies.26 The occurrence of a new severe headache is a red flag in a patient with SLE, and immediate evaluation is required.27,28
Mood disorder
Depressive affect may be a normal and appropriate reaction for an adolescent dealing with a chronic disease, and thus attribution of depression to SLE is often challenging, and requires input from psychiatry colleagues. Major depression is not as frequent, and occurs in fewer than 10 – 20% of patients.28,29
Cognitive dysfunction
Impairment of cognition may be manifested by declining school performance and subtle difficulties with working memory and concentration tasks.Children With Lupus Essay. Cognitive dysfunction is diagnosed with traditional neuropsychological testing, and has been observed in more than a third of asymptomatic cSLE patients.29-31
Psychosis
Hallucinations, predominantly visual but also auditory, are experienced by more than 10% of all patients with cSLE. Visual distortions are also common, with children reporting that the clock or light is distorted, or that the words on the page are “popping out”. The psychosis differs from that of primary psychiatric disease in that SLE patients have preserved insight, however, evaluation by a psychiatrist is recommended to assist with the diagnosis. Psychosis is frequently concomitant with cognitive dysfunction and acute confusional state.24 Although investigations including MRI are often normal, aggressive treatment is recommended and frequently leads to complete resolution of symptoms.32,33
Children With Lupus Essay
