9.7 Immunodeficiency and Oral HIV Manifestations

3. Immunodeficiencies: Primary Disorders and Secondary HIV Manifestations

Primary Immunodeficiencies (Congenital)

1. Severe Combined Immunodeficiency (SCID): Heterogeneous genetic disorders characterised by absent or dysfunctional T and B lymphocytes. The most common form is X-linked SCID, caused by mutations in the IL2RG gene encoding the common gamma chain (γc) shared by cytokine receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Lack of IL-7 signaling arrests T-cell development, while lack of IL-15 arrests natural killer (NK) cell development. Clinically presents within the first months of life with intractable diarrhea, failure to thrive, persistent pseudomembranous oral candidiasis, and fatal opportunistic pulmonary infections (Pneumocystis jirovecii).
2. X-Linked Agammaglobulinaemia (Bruton's Disease): Mutation in the BTK gene on the X chromosome encoding Bruton tyrosine kinase. BTK is essential for B-cell maturation beyond the pre-B stage. Affected males have virtually zero circulating mature B lymphocytes (CD19+, CD20+) and a profound deficiency of all immunoglobulin classes (IgG, IgA, IgM, IgE). T-cell immunity remains intact. Patients become susceptible to recurrent pyogenic infections caused by encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae) starting at 6 months of age, following the physiological clearance of transplacentally acquired maternal IgG.
3. Chediak-Higashi Syndrome: Autosomal recessive disorder caused by mutations in the LYST (lysosomal trafficking regulator) gene. Disrupted vesicular trafficking produces abnormal, giant cytoplasmic lysosomal granules in all granulated cells, including neutrophils, melanocytes, and platelets. Neutrophils exhibit severe defects in chemotaxis and delayed phagolysosomal degranulation. Clinically characterised by partial oculocutaneous albinism, recurrent pyogenic infections, peripheral neuropathy, and rampant, aggressive, early-onset periodontitis causing premature loss of all deciduous and permanent teeth.

Secondary Immunodeficiencies: Human Immunodeficiency Virus (HIV / AIDS)

HIV is an enveloped retrovirus possessing two identical single-stranded RNA molecules. The viral envelope glycoprotein gp120 binds to the CD4 receptor on host helper T cells, macrophages, and dendritic cells, inducing a conformational change that enables secondary binding to chemokine coreceptors (CCR5 in macrophage-tropic strains; CXCR4 in T-cell-tropic strains). Subsequently, viral gp41 mediates fusion of the viral envelope with the host membrane. Progressive viral replication depletes CD4+ T lymphocytes, collapsing cell-mediated immunity. An absolute CD4 count <200 cells/μL (or a CD4 percentage <14%) defines the diagnosis of AIDS.

Oral Manifestations of HIV Infection

Oral lesions are among the earliest, most sensitive clinical biomarkers of HIV infection, tracking viral load and CD4 decline:

                             ORAL MANIFESTATIONS OF HIV
                                         │
         ┌───────────────────────────────┼──────────────────────────────┐
         ▼                               ▼                              ▼
[Fungal Infections]            [Viral Infections]             [Periodontal / Neoplastic]
 • Pseudomembranous Candidiasis  • Oral Hairy Leukoplakia      • Linear Gingival Erythema (LGE)
 • Erythematous Candidiasis       (EBV; non-malignant)         • Necrotising Periodontitis (NUP)
 • Angular Cheilitis            • Kaposi Sarcoma (HHV-8)        • Non-Hodgkin Lymphoma (EBV)

1. Oral Candidiasis: The most common intraoral opportunistic infection in HIV, occurring in over 85–90% of untreated AIDS patients:
   • Pseudomembranous (Thrush): Creamy white, curd-like plaques on the labial/buccal mucosa, tongue, and soft palate. Composed of fungal hyphae, desquamated epithelial cells, and necrotic debris. Characteristically wipes away with dry gauze, leaving a raw, erythematous, or bleeding base.
   • Erythematous (Atrophic): Presents as smooth, fiery red macules or depapillated atrophic patches, characteristically on the hard palate and dorsum of the tongue. Frequently overlooked because it lacks the classic white plaques of thrush. It is a highly sensitive clinical harbinger of severe immunosuppression.
   • Angular Cheilitis: Erythema, maceration, and fissuring radiating from the oral commissures, frequently representing a mixed infection (Candida albicans and Staphylococcus aureus).
2. Oral Hairy Leukoplakia (OHL): Caused by opportunistic replication of Epstein-Barr Virus (EBV / HHV-4) within the spinous keratinocytes of the oral epithelium. Clinically presents as non-wipeable, asymptomatic, corrugated, vertically folded or "hairy" white plaques located almost exclusively on the lateral borders of the tongue (unilateral or bilateral). Histologically displays hyperparakeratosis, epithelial acanthosis, and upper prickle cells displaying nuclear clearing and peripheral chromatin beading ("koilocyte-like" ballooning cells). Crucially, OHL has zero malignant potential and does not require surgical excision; it serves as a clinical biomarker of disease progression and typically resolves upon initiation of effective antiretroviral therapy (ART).
3. Kaposi Sarcoma (KS): A malignant vascular neoplasm driven by Human Herpesvirus 8 (HHV-8 / KSHV). It is the most common intraoral malignancy in HIV/AIDS. Most commonly affects the hard palate (>50% of intraoral lesions) and attached gingiva. Lesions begin as asymptomatic flat, red, purple, or brown macules that evolve into elevated, spongy, vascular plaques and large, lobulated, exophytic masses that bleed easily on mastication. Histology reveals proliferating fascicles of spindle-shaped endothelial cells surrounding slit-like vascular channels with extravasated erythrocytes and hemosiderin pigment.
4. Linear Gingival Erythema (LGE): A distinctive form of gingivitis presenting as a persistent, continuous 2–3 mm fiery red band along the free and attached gingival margin. It occurs independently of plaque levels and fails to resolve with conventional scaling and improved oral hygiene alone. Subgingival colonization by Candida species is heavily implicated; therapy requires chlorhexidine rinses and topical antifungals.
5. Necrotising Periodontal Diseases (NUG and NUP):
   • Necrotising Ulcerative Gingivitis (NUG): Acute, excruciatingly painful condition characterised by necrosis and ulceration of the interdental papillae ("punched-out", crater-like papillae) covered by a friable grayish pseudomembrane, spontaneous gingival haemorrhage, and intense fetor oris.
   • Necrotising Ulcerative Periodontitis (NUP): Rapid progression of necrosis involving the periodontal ligament and alveolar bone. Produces catastrophic, deep osseous destruction, tooth mobility, and exposure of necrotic bone sequestra within days to weeks. Associated with an anaerobic fusospirochaetal complex (Treponema spp., Prevotella intermedia, Fusobacterium nucleatum).
   • Management: Gentle debridement with warm saline / ultrasonic instrumentation, chemical biofilm suppression with 0.2% chlorhexidine or 1.5% hydrogen peroxide mouthwashes, systemic metronidazole (400 mg three times daily for 3–5 days), pain management, and urgent communication with the patient's HIV physician.

4. Clinical Application: Worked Examples and Traps

Clinical Trap: Inappropriate Prescribing for Suspected "Denture Stomatitis"

A common diagnostic error is assuming all palatal erythema beneath a maxillary complete denture represents benign Newton Type II denture-related stomatitis. If the patient is young, does not wear a denture, or if the palatal erythema is accompanied by weight loss or generalized lymphadenopathy, the practitioner must suspect erythematous candidiasis secondary to undiagnosed HIV infection or severe immunosuppression. Direct questioning regarding risk factors, full medical review, and referral for serological HIV screening are warranted.

Worked Clinical Example

Scenario: A 64-year-old female is referred by her general dental practitioner with a 6-month history of painful, "bleeding gums". Clinical examination reveals generalized fiery red desquamative gingivitis involving the labial and lingual attached gingiva of both arches, along with two intact tense bullae on the hard palate. Routine gentle brushing causes superficial mucosal detachment. The patient also mentions that her eyes have felt "gritty and dry" for the past three weeks.

Diagnostic & Treatment Protocol:

1. Clinical Suspicion: The presence of tense intraoral bullae, desquamative gingivitis, and ocular grittiness points strongly to Mucous Membrane Pemphigoid (MMP).
2. Diagnostic Biopsy: Perform two perilesional punch biopsies:
   • Specimen A (in 10% neutral buffered formalin for light microscopy): Expect subepithelial clefting at the BMZ with an intact, full-thickness epithelial roof and an absence of acantholysis.
   • Specimen B (in Michel's transport medium for Direct Immunofluorescence): Expect a continuous linear band of IgG and C3 strictly along the basement membrane zone.
3. Immediate Clinical Action: Instigate an immediate, urgent referral to an ophthalmologist for baseline slit-lamp evaluation. Early subconjunctival cicatrization must be identified to prevent symblepharon formation and irreversible blindness.