Polyuria, Polydipsia and Papules in a 9-Year-Old Girl: A Case Report

    

    

    Figure 1D: Dermatoscopic view, lesions each a few millimeters in size.
    

The patient is admitted for rehydration, initiation of insulin therapy, diabetes education and stabilization of the patient’s hyperglycemia. Investigation reveals an extensive history of familial hypertriglyceridemia and multiple family members with myocardial infarctions at a young age. The patient’s mother denies any family history of diabetes, celiac disease, thyroid disease, or other autoimmune diseases. When serological tests are drawn, the blood appears chylous and milky white. The triglyceride level is 2,672mg/dL [30.19mmol/L] (reference range, 34-149 mg/dL [0.38-1.68 mmol/L]), cholesterol is 735mg/dL [19.04mmol/L] (reference range, 0-199 mg/ dL [0-5.15 mmol/L]), and HDL is 27mg/dL [0.70mmol/L] (reference range, 0-80 mg/dL [0-2.07 mmol/L). The LDL and VLDL are not calculated, as the patient’s triglyceride level is greater than 400mg/ dl [4.52mmol/L].

Diagnosis

The cutaneous findings are characteristic of eruptive xanthomas, which typically indicate systemic hyperlipidemia. Xanthomas appear as yellow papules with a faint erythematous ring, they range from 1 to 4 mm in diameter and are rarely pruritic or painful.

Discussion

The case at hand describes a 9-year-old female with hypertriglyceridemia secondary to uncontrolled T1DM due to new diagnosis, with subsequent eruptive xanthomas. Physiologically, T1DM is characterized by insulinopenia. Lack of insulin activates lipolysis in adipose tissue releasing increased free fatty acids, which accelerates formation of very-low-density lipoprotein (VLDL) in the liver. Insulin is necessary to activate lipoprotein lipase, a key step in the catabolism of triglycerides. Reduced activity of lipoprotein lipase in peripheral tissue decreases removal of VLDL from the plasma, resulting in hypertriglyceridemia [1,2].

Xanthomas usually emerge on the extensor surfaces of the arms, legs, hands and buttocks but also can develop in tendinous regions, fasciae, and bone [3]. Histologically, xanthomas are composed of a dermal infiltrate of foamy macrophages with surrounding inflammatory cells [4,5]. The literature reports self-resolution of these cutaneous findings within weeks to months of adequate diabetic control; however, adult patients are often initiated on triglyceride lowering medications as the risk of pancreatitis and coronary artery disease is greater in this population [4,6]. In cases where the size or location is bothersome, xanthomas can be surgically excised; however, vigilant surgical management is essential, as recurrence is more likely with incomplete excision [7].

Common misdiagnoses include molluscum contagiosum, juvenile xanthogranulomas, papular acrodermatitis, or a viral exanthem. Molluscum contagiosum, the initial diagnosis for this case, is a viral infection of papules with central umbilication that appear on frictionprone surfaces (axillae, genitalia). In contrast, our patient’s papules lacked central umbilication and were found on extensor surfaces. A rare finding but also confused with eruptive xanthoma is juvenile xanthogranuloma. These red, yellow, or brown papules are benign, non-Langerhans cell histiocytosis that appear as solitary lesions of the upper body; multiple juvenile xanthogranulomas are rare but observed in Neurofibromatosis Type 1 (NF-1) patients that have and increased risk of hematologic cancer [8]. The presence of multiple papules on the lower extremities in the setting of hypertriglyceridemia make the diagnosis of juvenile xanthogranulomas less likely. Another differential diagnosis to consider is papular acrodermatitis of childhood, otherwise known as Gianotti-Crosti syndrome. Typically present in young children, papular acrodermatitis manifests as skin colored vesiculopapular lesions sometimes in conjunction with viral symptoms. These self-limited lesions arise on the face, buttocks, or acral regions and may last up to several months [9]. Given the patient’s historical paucity of any viral symptoms or vesicular findings, papular acrodermatitis or viral exanthem are less likely to be the correct diagnosis.

Xanthomas can occur in a normolipemic patient or a patient with underlying hypertriglyceridemia [5]. In normolipemic patients, eruptive xanthomas form due to increased vascular permeability to chylomicron particles. Thus, the pathogenesis for eruptive xanthomas in normolipemic patients can be secondary to trauma, histiocytosis, juvenile xanthogranuloma, xanthoma disseminatum or papular xanthoma. These patients lack laboratory hyperlipidemia but have lipid-laden reactive cells or undergo spilling of lipoproteins into the dermis which are then phagocytosed by dermal histiocytes [5,10]. In patients with underlying hypertriglyceridemia, eruptive xanthomas develop secondary to familial dyslipidemia or an acquired disease. Eruptive xanthomas most commonly emerge in type V hyperlipoproteinemia, but can also be present in Type 1 hyperlipoproteinemia, Type 1a lipoprotein lipase deficiency, and other familial dyslipidemias [4,5]. Uncontrolled type one and two diabetes, metabolic syndrome, hypothyroidism, and nephrotic syndrome have all been reported to cause eruptive xanthomas. In addition, other factors such as alcohol abuse, retinoid therapy, estrogen supplementation, and metabolic syndrome have been associated with eruptive xanthomas [1,8,11]. Rarely, a child with xanthomas may report pruritus, which should prompt the practitioner to rule out cholestasis; this specific constellation of xanthomas, pruritus, and cholestasis should raise suspicion for Alagille syndrome, primary biliary cholangitis, biliary atresia, or other obstructive biliary processes [12]. Xanthomas present on the palm, flexural surfaces of the fingers and within the skin, folds are typically associated with biliary cirrhosis; in contrast, xanthomas on the palmar crease alone are more specific for familial dysbetalipoproteinemia type III [7].

Patient Course

After discharge, the patient followed regularly with her endocrinologist for continuing management of type one diabetes mellitus, confirmed by positive specific T1DM antibodies. She achieved excellent metabolic control with 71% time-in-range based on her Continuous Glucose Monitoring System; she maintained a low-fat diet on subcutaneous insulin. A second lipid panel was drawn four months later revealing triglycerides 88mg/dL [0.99mmol/L] (reference range 0 - 89 mg/dL [0-1.02 mmol/L]), cholesterol 195mg/dL [5.05mmol/L] (reference rage 100-169 mg/dL [2.59- 4.38 mmol/L]), and HDL 47mg/dL [1.22mmol/L] (reference range, >39mg/dL [>1.01mmol/L]). The patient’s cutaneous manifestations had improved at four weeks and completely resolved within four months without any additional management.

References

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