A case of dual pathologies: Kaposi varicelliform eruption superimposed on acrodermatitis enteropathica

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A 20-year-old man presented with itchy pustular lesions, initially on his face and later spreading to his trunk and extremities. His parents reported him having relapsing and remitting oozing lesions for 3 months of age over the perineal, gluteal, and perioral regions. He was born as a full-term normal vaginal delivery to parents with third-degree consanguineous marriage with no history of diarrhoea or psychiatric complaints. He was of normal built. A dermatological examination revealed well-defined erythematous papules and pustules on the trunk, limbs, and gluteal region [Figure 1a]. Crusted plaques were present on the malar area and at the angles of the mouth, with oral candidiasis [Figure 1b]. Erosions with serous discharge were found in the toe webspaces [Figure 1c].

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Figure 1:

(a) Multiple erythematous plaques with serous discharge present in the groin folds, (b) Multiple crusted plaques present over malar area and perioral region, (c) Erythematous plaque with serous discharge present over the web spaces.

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Differential diagnoses included acrodermatitis enteropathica (AE), pellagroid dermatitis and biotinidase deficiency with folliculitis, Leiner’s disease, and complement deficiency disorder as tabulated in Supplementary table 1.^1-7 Laboratory investigations showed a zinc level of 70.83 µg/dL (normal: 70–120 µg/dL), serum alkaline phosphatase- 26 U/L (normal: 40- 130 U/L), elevated IgE (882 IU/mL; normal <100 IU/mL), total protein- 8.0 g/dL (normal-6.4 to 8.3), albumin – 4.8 gm/dL (normal- 3.2 to 4.8), A/G ratio- 1.5% (normal- 1.0 to 2.0) and neutrophilic leukocytosis. Viral markers like HbsAg, HIV, and Hepatitis C virus were negative. The renal and liver function tests were normal. Histopathology revealed intraepidermal clefts, spongiosis, and pallor in the upper part of the epidermis, suggestive of AE [Figure 2a, 2b]. The diagnosis was confirmed on genetic testing, which revealed a mutation in exon 10 of the SLC39A4 gene.

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Figure 2:

(a) Blue star denotes the intraepidermal split, orange star denotes spongiosis (Haematoxylin & eosin, 10x) (b) Blue star denotes the intraepidermal split, orange star denotes spongiosis, blue arrow denotes orthokeratosis with parakeratosis, orange arrow corresponds to pallor of upper part of epidermis (Haematoxylin & eosin, 40x).

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He was started on oral zinc (2 mg/kg/day) and fluconazole for oral candidiasis, with initial improvement in skin and oral lesions over two months. Subsequently, new papulovesicular and papulopustular lesions [Figure 3a] appeared, for which he was started on antibiotics with staphylococcal coverage, with partial response. Immunodeficiency workup comprising quantitative lymphocyte subset analysis and immunoglobulin profiles (IgG, IgA, IgM) was normal. Cultures, gram stain, and KOH testing from the lesions were negative. Tzanck smear from papulovesicular lesions on the trunk revealed multinucleated giant cells [Figure 3b] and elevated serum HSV IgG of 5.04 OD ratio (positive >1.20). Histopathology showed focal epidermal necrosis surrounding spongiosis with ballooning of keratinocytes and granulation tissue in the subepithelium. This led to the diagnosis of Kaposi varicelliform eruption on clinicopathological correlation. As lesions were not extensive and the patient refused admission, the patient was prescribed tab valacyclovir 1 gm twice daily for 10 days with previous literature reference and near complete resolution of lesions. ^1,2 Subsequent withdrawals of anti-viral medication resulted in a resurgence of lesions on two occasions. Hence, he was started on a suppressive dose of valacyclovir 1gm daily. The patient is currently in remission and has been advised to continue lifelong oral zinc supplementation.

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Figure 3a:

Multiple vesicular lesions present in the anterior aspect of the trunk.

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Figure 3b:

Multinucleated giant cells seen as highlighted by blue arrow (Giemsa stain, 40x).

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AE is an uncommon, autosomal recessive, hereditary condition due to a mutation in the zinc transport protein (ZIP 4) gene, SLC39A4, affecting zinc transport and absorption. Zinc is essential for hormone synthesis, growth, gene control, immunity, and enzymatic function.³ In our case, serum alkaline phosphatase, the sensitive indicator of AE, was low despite normal zinc levels, suggesting an erroneously normal zinc level. Zinc deficiency can be hereditary or acquired. Prematurity, low birth weight, zinc deficiency in the mother’s milk, parenteral nutrition, malabsorption syndromes (Crohn’s disease, celiac disease), alcoholism, low calcium/ phytate diet, and Kwashiorkor are reasons for acquired zinc insufficiency. AE manifests in children after weaning.³

Kaposi Varicelliform Eruption (KVE) was first described by Moritz Kaposi in the 19^th century and was later confirmed to be a viral infection in the 20^th century. It is a widespread cutaneous infection caused by the herpes simplex virus, commonly seen in individuals with pre-existing dermatitis, particularly atopic dermatitis. It appears over the head, neck, and trunk and is characterised by extensive clusters of umbilicated vesicopustules and eroded vesicles that alternate with punched-out ulcers coated with haemorrhagic crusts.² It primarily affects individuals with skin barrier damage or immune deficiencies, with studies showing faster Herpes simplex virus (HSV-1) replication in atopic dermatitis and psoriasis, linked to cytokine imbalances (low interferon gamma (IFN-γ), C-X-C motif chemokine ligand 10 (CXCL10), and cathelicidins; high IL-4 and IgE), T-cell defects, and reduced natural killer cells.²

This case is unique for the coexistence of AE and eczema herpeticum. While AE can mimic atopic dermatitis (AD), its complication with HSV infection is rare. Abnormal immune responses in AE, including elevated IgE and rheumatoid factor, have been reported, though their link to zinc deficiency is unclear. AE has also been associated with food allergies and specific IgE elevation.²