A 17-year old patient with DOCK8 deficiency, severe oral HSV-1 and aggressive periodontitis - a case of virally induced periodontitis?

Abstract

We present a 17-year old girl with DOCK-8 deficiency, severe untreated oral HSV-1 infection and associated aggressive periodontitis. DOCK-8 deficiency is a primary immunodeficiency, caused by biallelicloss-of-function mutations in the DOCK8 gene, often leading to severe viral and fungal mucocutaneous infections. Nevertheless, to date DOCK8 has not been associated with severe periodontitis and inflammatory bone loss around teeth. Understanding whether DOCK8 deficiency or severe HSV-1 infection underlies susceptibility to periodontitis is central to this case and may provide insights into susceptibility factors for periodontitis in the general population. Our clinical and microbiological data suggest that severe HSV-1 infection is the driver of periodontal inflammation in this case.

Keywords: Aggressive periodontitis; DOCK8 deficiency; Oral HSV-1.

Figure 1. Initial Clinical Oral Presentation and Diagnostic Radiographs

(A–D) Intraoral photography of widespread HSV-1 intraoral lesions. Ginigiva appear erythematous, edematous and necrotic. White coating is covering the majority of mucosa areas, indicative of sloughling necrotic epithelia. Areas shown are: facial surface of maxilla (A) and mandible (B) palatal (C) and lingual surfaces (D). (E) Panoramic radiograph. Severe bone loss is indicated by the two drawn lines. The white line represents the expected physiological bone level (a) and the black line (b) the actual bone level.

Figure 2. Oral Microbiology

(A) Diagnostic Microbiology on oral swabs and dental plaque. (B) 16S microarray for approximately 300 oral species (HOMIM) was performed on subgingival dental plaque samples (Percentage of detection throughout all teeth sampled). Classic periodontitis-related species indicated with red arrows.

Figure 3. Oral Pathology

Histological evaluation of an ulcerated oral lesion. (A) H&E staining reveals ulcerated squamous mucosa with marked acute and chronic inflammation, granulation tissue and scattered multinucleated giant cells. (B) Multinucleated cells with cytopathic changes shown at higher magnfication (circled) and are positive for HSV-1 by immunohistochemistry (C, brown staining indicated by arrows). Original magnifications shown.

Figure 4. Clinical course of Disease

Intraoral photography at various time points of treatment (A–C). (A) Patient had received one year of Valacyclovir and was two weeks post periodontal treatment. Arrows indicate remaining areas of necrosis and erythema. (B) Following 5 days of immunosuppressive conditioning prior to transplant. Images (A) and (B) are taken 7 days apart. (C) 100 days post HCT. Black lines on teeth indicate areas tissue shrinkage (recession) resulting from inflammatory resolution. D. Full mouth probing depths in mm before periodontal treatment (pre) and at the end of the follow up period (post). Mean ± SE and range shown, *=p<0.01.