Ectopic atrial tachycardia in an infant with transient erythroblastopenia of childhood

Transient erythroblastopenia of childhood is a self-limited anemia occurring in previously healthy children, secondary to temporary cessation of erythrocyte production. Although the precise etiology is unclear, most cases are associated with a viral illness. The anemia may be severe, with associated pallor, tachypnea, and tachycardia; treatment is supportive. We present an unusual case of a child with viral-induced transient erythroblastopenia of childhood and associated ectopic atrial tachycardia, requiring therapy with antiarrhythmics.     

Cholelithiasis in a toddler with sickle cell disease

Cholelithiasis is rarely seen in toddlers and school-aged children, even in the setting of sickle cell anemia. In addition to more common etiologies, such as gastroenteritis, constipation, and urinary tract infection, the differential diagnoses of acute abdominal pain in young children with sickle cell disease include vaso-occlusive pain crisis and splenic sequestration. We describe a case of a toddler with sickle cell disease initially presenting with abdominal pain who was found to have symptomatic cholelithiasis.     

Prognostic Implications of Cutaneous Immunoglobulin Deposits In Systemic Lupus Erythematosus

The class of immunoglobulin (Ig) deposited at the dermal-epidermal junction (DEI) of the skin in patients With systemic lupus erythematosus (SLE) has been proposed to have prognostic implications. The authors studied disease activity in 51 SLE patients with a positive lupus band. Patients with cutaneous IgM deposits had significantly more severe disease than those with only IgG or with mixed immunoglobulin deposits. While their data suggest an association between IgM depostis, severe disease and a poor prognosis, they urge caution in utilizing Ig deposits as a prognostic indicator.     

The law of mass action and the pharmacological concentration–effect curve: resolving the paradox of apparently non‐dose‐related adverse drug reactions

Background

Adverse drug reactions are sometimes described as being ‘non‐dose‐related’ because no relationship has been found between increasing doses and either the intensity of the response or the proportion of individuals in whom the response occurs; furthermore, hypersensitivity reactions are often regarded as being non‐dose‐related, even if different doses have not been studied. However, the law of mass action implies that all pharmacological effects are concentration related and should increase in intensity with increasing dose. We set out to explain this paradox.

Methods

We searched for published adverse drug reactions that have been described as non‐dose‐related and analysed them.

Results

We identified four categories of explanations that resolve the paradox: (i) the reaction is not real; it may have occurred by chance or there may be methodological problems, such as bias or confounding factors; (ii) the dose–response curve for the adverse effect reaches a maximum at doses lower than were studied (i.e. a hypersusceptibility reaction); this underpins the use of test doses to predict the possibility of an adverse reaction at therapeutic doses; (iii) susceptibility to the adverse reaction differs widely among individuals; and (iv) imprecision or inaccuracy in the measurement of either dose or effect obscures dose responsiveness. This last explanation encompasses: (a) reactions related to cumulative dose; (b) dissociation between dose and concentration through saturable pharmacokinetics; and (c) variability in the measurement of the effect.

Conclusions and implications

If an adverse drug reaction appears to be non‐dose‐related, the reasons should be sought, having these mechanisms in mind.