Introduction to Sjögren Syndrome in Children

Sjögren syndrome is a chronic, inflammatory, autoimmune disease characterized by progressive lymphocytic and plasma cell infiltration of the salivary and lacrimal glands.

Epidemiology.
Sjögren syndrome typically presents at 35–45 yr of age, with 90% of cases among women. It is uncommon in the pediatric age group. Sjögren syndrome can occur as an isolated disorder, referred to as primary Sjögren syndrome (sicca complex), or as a secondary form in association with other rheumatic disorders.

Etiology And Pathogenesis.
The etiology of Sjögren syndrome is complex and includes genetic predisposition, and possibly an infectious trigger. Lymphocytes and plasma cells infiltrate salivary glands, forming distinct periductal and periacinar foci that become confluent and may replace epithelial structure. This autoimmune exocrinopathy results in xerophthalmia (dry eyes, or keratoconjunctivitis sicca) and xerostomia (dry mouth). Several genes regulating apoptosis influence the chronicity of lymphocytic infiltration.

Clinical Manifestations.
International classification criteria for the diagnosis of Sjögren syndrome in adult patients have been developed, and diagnostic criteria in children have been proposed. Clinical manifestations are related to exocrine disease of the epithelial surfaces of the eyes, mouth, nose, larynx and trachea, vagina, and skin, leading to the common symptoms of photophobia, burning and itching eyes, blurred vision, painless unilateral or bilateral enlargement of the parotid glands, decreased sense of taste, dental caries, dysphagia, fissured tongue, and angular cheilitis. At the onset of the disease, recurrent parotid gland enlargement and parotitis is the most common manifestation in children, whereas sicca manifestations are most common in adults.

Severe combined immunodeficiency disease

Both cell-mediated (T-cell) and humoral (B-cell) immunity are deficient or absent in severe combined immunodeficiency disease (SCID). This results in susceptibility to infection from all classes of microorganisms during infancy.

At least three types of SCID exist: 

1. reticular dysgenesis, the most severe type, in which the hematopoietic stem cell fails to differentiate into lymphocytes and granulocytes; 
2. Swiss-type agammaglobulinemia, in which the hematopoietic stem cell fails to differentiate into lymphocytes alone; and 
3. enzyme deficiency, such as adenosine deaminase (ADA) deficiency, in which the buildup of toxic products in the lymphoid tissue causes damage and subsequent dysfunction.

Incidence
SCID affects more males than females; its estimated incidence is 1 in every 100,000 to 500,000 births. Most untreated patients die from infection within 1 year of birth.

Causes
SCID is usually transmitted as an autosomal recessive trait, although it may be X-linked. In most cases, the genetic defect seems associated with failure of the stem cell to differentiate into T and B lymphocytes.
Many molecular defects, such as mutation of the kinase ZAP-70, can cause SCID. X-linked SCID results from a mutation of a subunit of the interleukin-2 (IL-2), IL-4, and IL-7 receptors. Less commonly, it results from an enzyme deficiency.

Treatment Options for SLE in Children

The treatment regimen depends on the affected target organs and disease severity. Sun exposure should be minimized and include use of a sunscreen. Patients are treated to promote clinical well-being, using serologic markers of disease activity as guidelines, including serum complement levels. Nonsteroidal anti-inflammatory agents, used to treat arthralgia and arthritis, are used with caution because patients with lupus are more susceptible to hepatotoxicity. Hydroxychloroquine is often used to treat mild manifestations including skin lesions, fatigue, arthritis, and arthralgia. Hydroxychloroquine may also reduce the risk of thromboembolic disease and lowers lipid levels.

Patients with thrombosis and antiphospholipid antibodies or a lupus anticoagulant should receive anticoagulant medication at least until lupus is in remission. The length of therapy is controversial. Low molecular weight heparin is the anticoagulant of choice; warfarin can also be used.

Corticosteroids control symptoms and autoantibody production in lupus. Treatment with corticosteroids has improved kidney disease and the rate of survival. Corticosteroids can make the diagnosis and treatment of tuberculosis difficult; all patients should have PPD and control skin tests, when possible, before corticosteroids are initiated. The optimal dose and route of administration of corticosteroids are controversial. Patients with systemic disease are often started on 1–2 mg/kg/24 hr of oral prednisone in divided daily doses. When complement levels increase to within the normal range, the dose is carefully tapered to the lowest effective dose. One method uses alternate-day high-dose corticosteroids once disease is controlled to prevent the adverse effects of daily corticosteroid administration. Severely ill patients may require pulse intravenous corticosteroid therapy (30 mg/kg/dose, maximum 1 g/day, given over 60 min, for 3 days). Intermittent high-dose intravenous therapy in combination with low-dose daily oral corticosteroids has been used as an alternative regimen in some centers. Adverse effects of corticosteroids include hypertension, gastritis, cataracts, osteopenia, and cushingoid body habitus.

Immunologic Drug Eruptions in Children

Cutaneous adverse reactions to drugs are common in pediatric practice and often present a diagnostic challenge.

Pathogenesis:
The pathogenesis of most drug eruptions is not well understood. With few exceptions, eg, fixed drug eruption, the diagnosis cannot be based solely on the morphology of the eruption.

Clinical Features:
A drug rash may manifest as urticaria, a morbilliform exanthem, erythroderma, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), photosensitivity, lichen planus, or vasculitis, all of which have other potential causes. A high index of suspicion for drug causation is important so that an offending drug is discontinued and avoided in the future, particularly in the case of life-threatening reactions such as anaphylaxis, the drug (anticonvulsant) hypersensitivity syndrome, SJS, and TEN. Conversely, it is important not to err by labeling a child as allergic to a widely used medication, such as penicillin. There are no standardized laboratory investigations that are diagnostic for drug allergy, and the value of allergy testing is largely restricted to cases of IgE-mediated penicillin hypersensitivity. Therefore, a detailed history, evaluation of the morphology of the rash, consideration of a differential diagnosis, and careful clinical judgment are essential.
The timing of the reaction may be helpful. Medications begun recently, particularly within the past weeks, are more likely to be culpable than drugs taken for many months.

Urticaria usually occurs within hours to one day after beginning a medication, whereas maculopapular eruptions develop 7 to 10 days into treatment unless there has been a previous exposure.

Life-threatening hypersensitivity reactions to sulfonamides, carbamazepine, phenytoin, or phenobarbital characteristically occur one to four weeks after initiating therapy. Although serious adverse reactions are rare, the parents of children who are prescribed these medications should be advised to seek medical attention if a rash or fever develops within the first four to six weeks of treatment.

The morphology of the rash is an important observation. 

Atopic Dermatitis (Eczema)

Atopic dermatitis is a chronic relapsing and remitting inflammatory skin disease characterized by dermatitis with typical morphology and distribution.

Eczema is a generic term for a constellation of clinical signs, whereas atopic dermatitis is a term that specifically connotes an allergic contribution to the etiology of the eczema.

The overall prevalence of atopic dermatitis in the United States is 17% among school-aged children, leading to considerable disease-related morbidity, including irritability, secondary skin infections, sleep disturbance, school absenteeism, and poor self-image.

History

• Age of onset is a consideration, with 45% of affected individuals manifesting atopic dermatitis in the first 6 months of life, 60% by the first year, and 85% by school age.
• Pruritus is a cardinal feature of eczema, often described as the “itch that rashes.” Scratching leads to further compromise in the skin barrier and augments inflammation.
• Xerosis (dry skin) also involves nonlesional skin. (In other conditions, commonly mistaken for atopic dermatitis (seborrheic dermatitis, nummular eczema, and psoriasis), the uninvolved skin is generally healthy.)
• Patients may have a personal and family history of atopy (asthma, hay fever, food allergy).
• Exacerbating factors include food allergens (most frequently egg, milk, wheat, soy, peanut, tree nuts, shellfish) and inhalant allergens (e.g., pet dander, house dust mite).
• Systemic involvement, with failure to thrive, chronic diarrhea, and/or recurrent infections should prompt consideration of underlying systemic disease, such as immunodeficiency (e.g., Wiskott-Aldrich syndrome, Netherton syndrome, immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, and hyper-IgE syndrome), or malabsorption (e.g., zinc deficiency or cystic fibrosis).

Physical Examination

• Xerosis (dry skin)
• Morphology of lesions
• Acute lesions: pruritic papules with excoriation and serous exudation
• Chronic lesions: lichenified papules and plaques
• Superficial linear abrasions from scratching
• Indistinct lesional borders, unlike that of psoriasis

Management Of Anaphylaxis In Emergency Room

Definition of Anaphylaxis
Anaphylaxis is the clinical syndrome of immediate hypersensitivity. It is characterized by cardiovascular collapse, respiratory compromise and cutaneous and GI symptoms ( e.g urticaria, emesis )

Initial Management

1. ABC’s : Establish airway if necessary. Assess breathing. Supply with 100% oxygen with respiratory support as needed. Assess circulation and establish IV access. Place patient on cardiac monitor.

2. Epinephrine: Give epinephrine , 0.01 ml/kg (1:1000) intramuscular, maximum dose 0.5 ml. Repeat every 15 min as needed. The site of choice is lateral aspect of thigh due to its vascularity.

3. Albuterol: Give nebulized albuterol, 0.05 to 0.15 mg/kg in 3 ml normal saline solution ( quick estimate 2.5 mg for < 30kg and 5 mg for > 30kg ) every 15 min as needed.

4. Histamine 1- receptor antagonist: such as diphenhydramine, 1-2 mg/kg through IV.IM or oral route. Also consider a histamine -2 receptor antagonist.

5.Corticosteroids: helps prevent the late phase of allergic response. Administer methlyprednisolone in a 2 mg/kg IV bolus, then 2mg/kg per day IV or IM divided every 6 hrs or prednisone 2 mg/kg PO in a bolus once daily. Observe for 6 to 24 hrs for late phase symptoms depending on clinical condition and stability.

List Of Anatomic And Mucociliary Defects That Result In Recurrent Or Opportunistic Infections

The major components of host defense include an anatomic barrier, innate immunity and adaptive immunity. Integrity of the anatomic-mucociliary barrier at the interface between the body and its environment is essential for protection against infection. 

Here is a list of anatomic and mucociliary defects that can result in recurrent or opportunistic infections.

Anatomic defects in upper airways

• Aspiration syndromes ( gastroesophageal reflux, ineffective cough, foreign body )
• Cleft palate, eustachian tube dysfunction
• Adenoidal hypertrophy
• Nasal polyps
• Obstruction of paranasal sinus discharge
• Post-traumatic or congenital sinus tracts ( CSF rhinorrhea )

Anatomic defects in the tracheo-bronchial tree

• Tracheo-esophageal fistula, bronchobiliary fistula
• Pulmonary sequestration, bronchogenic cysts, vascular ring
• Tumor, foreign body or enlarged nodes

Physiologic defects in upper and lower airways

• Primary ciliary dyskinesia syndrome
• Cystic fibrosis, Bronchopulmonary dysplasia
• Bronchiectasis
• Allergic diseases (allergic rhinitis, asthma)
• Chronic cigarette smoke exposure