A Case of Refractory Psoriatic Erythroderma Associated with a Heterozygous Loss-of-Function Mutation in the Filaggrin Gene
Year: 2026
Type: article
Abstract: Dear Editor, Filaggrin gene mutations are the most common disease-causing single gene defects, associated with atopic dermatitis, contact allergy, asthma, hay fever, and peanut allergy. Psoriasis is a multifactorial disease, influenced greatly by genetics. Here, we report a case of refractory psoriatic erythroderma associated with a heterozygous loss-of-function mutation in the filaggrin gene. A 4-year-old baby presented with redness and scaling involving more than 90% of the body surface area since 6 months of age. The history of collodion membrane, prolonged labour, recurrent ear and chest infections was absent. Family history was unremarkable. On cutaneous examination, erythema and scaling covered the whole body with ectropion. The scales were large, white, and quadrilateral in shape [Figure 1a and b]. The rest of the cutaneous and systemic examination was within normal limits. There was no eosinophilia or raised IgE levels. With a differential diagnosis of lamellar ichthyosis, psoriasis, and atopic dermatitis, histopathology was sent, which showed features of compact hyperkeratosis with parakeratosis, hypogranulosis, acanthosis, with broad and short rete ridges, consistent with psoriasis [Figure 2]. The patient was started on oral cyclosporine at 5 mg/kg with subsidence of erythroderma. However, the patient developed new psoriatic plaques after stopping treatment. On restarting cyclosporine, the patient did not respond and went into erythroderma again. The patient was tried on etanercept without any response. In view of Netherton syndrome and monogenic psoriasis, genetic analysis was sent, which revealed a heterozygous mutation in the FLG gene (c.11176C>T). SPINK5 mutation was not detected. Repeat skin biopsy was performed, which was consistent with psoriasis again. Secukinumab could not be given as the patient could not afford and so we restarted on oral cyclosporine and acitretin, after which there was partial remission in the form of a decrease in erythema and scaling after one month of treatment. The patient is kept under regular follow-up.Figure 1: (a) Multiple well-defined, erythematous, scaly plaques over the trunk, and (b) erythema and scaling covering more than 90% of body surface areaFigure 2: Histopathology showed hyperkeratosis with parakeratosis, agranulosis, acanthosis, with broad and short rete ridges [H and E, X100]Filaggrin gene (FLG) mutations are among the most common and profound single-gene defects identified to date in the causation and modification of disease.[1]Filaggrin, which is processed from profilaggrin, is a key protein that facilitates terminal differentiation of the epidermis and formation of the protective skin barrier.[2]FLG mutation carriers have a greatly increased risk of common complex traits, including atopic dermatitis (which affects 42% of all mutation carriers), contact allergy, asthma, hay fever, and peanut allergy.[1] The strong influence of genetics on psoriasis is evidenced by the increased propensity of disease among first- and second-degree relatives of sufferers and higher concordance of disease among monozygotic than dizygotic twins.[3,4] Apart from major histocompatibility complex (MHC), the major genes associated with psoriasis belong to pathways of antigen presentation, Th1 and Th17 signalling, NF-kB and type-1 interferon signalling, and skin barrier function [Table 1].[3,4] Hu et al.[5] in their study identified homozygous p.K4022X mutation in FLG gene only occurred in psoriasis patients, and heterozygous p.K4022X mutation in FLG gene occurred in ichthyosis vulgaris, psoriasis, as well as normal individuals, which led them to postulate that loss of function mutation in both copies of FLG gene may be a definite indicator of psoriasis and heterozygous loss of function mutation can lead to various symptoms depending on environmental factors. Marked alteration of filaggrin expression has been found in psoriatic skin.[5]Table 1: Genes associated with psoriasis[ 3 , 4 ]This case is being reported due to the rare association of FLG gene mutation with psoriasis and its refractory nature. Future studies could elucidate the correlation between various genetic association of psoriasis and its severity and refractoriness. Author contributions JM SB, DB, AB has made significant contribution to literature search, data acquisition, manuscript preparation, manuscript editing. Declaration of patient consent Informed written consent was taken from the patient. Financial support and sponsorship None. Conflicts of interest No conflict of interest to disclosure.
Source: Indian Journal of Dermatology
Institution: Sriram Chandra Bhanja Medical College Hospital
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7161640560