PMC7251162_01
Clinical manifestations and diagnostic evaluation. (A) Images of the patient's generalized psoriatic rash in the trunk (left) and axilla (upper right) at the time of initial presentation. Magnified panel (lower right) illustrates features of plaque psoriasis. (B) Brain CT demonstrates areas of calcification in the cerebral cortex and basal ganglia. (C) Skin biopsy illustrates hallmark features of psoriasis including hyperkeratosis, dilated capillary loops with a perivascular lymphocytic infiltrate, mild dermal edema, and regular psoriasiform epidermal hyperplasia with elongation of the rete ridges. (D) Renal biopsy pathology (H&E, PAS, and Masson's stains) illustrates membranous nephropathy and mesangial hyperplasia. (E) Electron microscopy of renal tissue demonstrates electron-dense deposits along the basement membrane (8000x magnification). (F) Immunofluorescence of renal tissue reveals positive glomerular staining for IgG, complement C3 and C1Q. (G) Chest CT images illustrate small pleural effusion, diffuse ground-glass opacities, and emphysema of lower lobes.
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F1
The psoriatic plaques have mostly resolved (PGA-PsO score = 1) and features of ILD improved markedly on chest CT (Figures 3A,B; see Supplementary Figure 1 for side-by-side comparison of pre- and post-treatment images). Pulmonary function testing showed normalization of FEV1 and FVC, while DLCO and pulmonary hypertension (as measured by systolic PA pressure) also improved (Figure 3C; Supplementary Figure 1).
PMC7251162_02
Clinical manifestations and diagnostic evaluation. (A) Images of the patient's generalized psoriatic rash in the trunk (left) and axilla (upper right) at the time of initial presentation. Magnified panel (lower right) illustrates features of plaque psoriasis. (B) Brain CT demonstrates areas of calcification in the cerebral cortex and basal ganglia. (C) Skin biopsy illustrates hallmark features of psoriasis including hyperkeratosis, dilated capillary loops with a perivascular lymphocytic infiltrate, mild dermal edema, and regular psoriasiform epidermal hyperplasia with elongation of the rete ridges. (D) Renal biopsy pathology (H&E, PAS, and Masson's stains) illustrates membranous nephropathy and mesangial hyperplasia. (E) Electron microscopy of renal tissue demonstrates electron-dense deposits along the basement membrane (8000x magnification). (F) Immunofluorescence of renal tissue reveals positive glomerular staining for IgG, complement C3 and C1Q. (G) Chest CT images illustrate small pleural effusion, diffuse ground-glass opacities, and emphysema of lower lobes.
fimmu-11-00985-g0001.jpg
PMC7251162_02_fimmu-11-00985-g0001.jpg
F1
The psoriatic plaques have mostly resolved (PGA-PsO score = 1) and features of ILD improved markedly on chest CT (Figures 3A,B; see Supplementary Figure 1 for side-by-side comparison of pre- and post-treatment images). Pulmonary function testing showed normalization of FEV1 and FVC, while DLCO and pulmonary hypertension (as measured by systolic PA pressure) also improved (Figure 3C; Supplementary Figure 1).
Genetic evaluation of Aicardi-Goutieres syndrome. (A) Identification of a missense mutation in IFIH1 by whole-exome sequencing and pedigree of the patient's family. The proband shares the pathogenic mutation with his mother and younger brother. (B) Heat-map of RNA sequencing analysis illustrates upregulation of IFN-I-inducible genes in the proband compared to healthy controls. The mother and brother display a milder interferon signature compared to the proband.
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F2
Given the unusual combination of systemic features, whole exome sequencing (WES) was sent and the patient possessed a pathogenic variant in IFIH1 (c.G2336A:p.R779H; Figure 2A), which encodes melanoma differentiation-associated protein 5 (MDA5). Compared to healthy controls, the patient exhibited global upregulation of IFN-I-inducible genes (Figure 2B).
Treatment response to corticosteroids, cyclophosphamide, and tofacitinib after 3 months. (A) Post-treatment image of the skin illustrates resolution of generalized psoriasis in the abdomen and groin. (B) Repeat chest CT shows resolution of pleural effusion and improvement of ground-class opacities. (C) Comparison of key findings from pulmonary function test and echocardiogram pre- and 3 months post-treatment.
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F3
The psoriatic plaques have mostly resolved (PGA-PsO score = 1) and features of ILD improved markedly on chest CT (Figures 3A,B; see Supplementary Figure 1 for side-by-side comparison of pre- and post-treatment images). Pulmonary function testing showed normalization of FEV1 and FVC, while DLCO and pulmonary hypertension (as measured by systolic PA pressure) also improved (Figure 3C; Supplementary Figure 1).