The first patient is a white female who was diagnosed at the age of 15; she had a long-standing history of severe psoriasiform dermatitis affecting her entire body but sparing the palms (Figures 249S-1A-C), along with chronic arthralgias, small stature, microcephaly, delayed puberty and intellectual disability.1 Skin was normal at birth and dermatitis was first noted around her umbilicus at the age of 2. It subsequently progressed to her back and trunk with generalization to the remainder of her body by the age of 6. The dermatitis worsens in the winter or when the patient is under stress; it only partially responded to standard anti-inflammatory therapy. Notably, the patient also has a medical history of congenital cataracts, mild developmental delay, microcephaly (at age 13, her head circumference was 53.5 cm, which is under the third percentile for her age and in the 50th percentile for a 7 ½ year old), and failure to thrive. Her height tracked along the third percentile between 9 and 39 months of age, but at age 13, her weight was 28.6 kg (under the third percentile and within the 50th percentile for a 9-year-old), and her height was 140 cm (under the third percentile, and within the 50th percentile for a 10 ½ year old). A skeletal survey showed delayed skeletal maturation, but otherwise there were no diagnostic findings. A skin biopsy showed psoriasiform hyperplasia, dilated capillaries in the dermal papillae, and neutrophils in the epidermis and stratum corneum (Figure 249S-1D). Neutrophil elastase staining of neutrophils in the stratum corneum is shown in red in Figure 249S-1F. While this histology was initially interpreted as being consistent with psoriasis, closer examination of the tissue revealed the presence of several foamy cells in the dermis. Oil red O staining (Figure 249S-1E) revealed intracellular lipid in these cells, reminiscent of that reported in patients with congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome.2 However, they were CD68 negative, indicating that they were not macrophages, a distinct difference from CHILD syndrome and verruciform xanthoma. Immunohisochemistry and hematoxylin and eosin-stained sections suggested that these cells were lipid-laden fibroblasts. Taken together, the histologic features are consistent with a psoriasiform dermatitis with some features of a verruciform xanthoma (Figures 249S-1D-E). In light of the psoriasiform changes, traditional therapies for psoriasis were implemented for the patient, including topical corticosteroids, calcipotriene, cyclosporine A, etanercept, phototherapy, and oral isotretinoin. However, while her skin briefly improved with cyclosporin A treatment, her symptoms did not exhibit a long-term response to any of the therapies. Subsequent additional evaluation revealed markedly elevated levels of serum IgE (1,486 IU/mL; normal <180) and IgA (684 IU/mL; normal <218). Her serum lipid profile showed a persistently low total cholesterol level (85 mg/dL; normal 140-176), low HDL (28 mg/dL; normal 35-75), and low LDL (49 mg/dL; normal 70-160), but normal triglycerides (84 mg/dL; normal 50-200) and VLDL (8 mg/dL; normal 8-14).
The second patient was diagnosed at 2 years old. She is a Hispanic female who presented with microcephaly, congenital cataracts, and developmental and growth delays. She has joint contracture most prevalent in the lower extremities. Her serum total cholesterol levels approximate 90 mg/dL.3