Severe combined immunodeficiency (SCID) with pigmentary mosaicism: A coincidental occurrence in a child

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Children with primary immunodeficiency syndromes present with a broad variation of clinical features, and the consequences are often severe if not promptly recognised. Here we report a 7-month-old male infant with a non-healing ulcer at the Bacillus Calmette-Guerin (BCG) site, multiple eczematous skin lesions, and pigmentary mosaicism with DCLRE1C (ARTEMIS) gene mutations to highlight the importance of cutaneous findings in early diagnosis of severe combined immunodeficiency (SCID).

A 7-month-old male infant born out of a non-consanguineous marriage presented with a non-healing ulcer over the BCG site and red, raised, scaly lesions over the body for the last five months. The lesions were first seen over the neck and gradually started to involve the trunk, extremities, and buttocks over a span of five months. Around the same time, the patient developed a pea-sized swelling over the BCG scar site, which gradually gave rise to a non-healing ulcer associated with intermittent pus discharge. He was born at full term via normal vaginal delivery, second birth order and birth weight was 2.8 kg. The elder brother was completely asymptomatic, while there was a history of abortion at five months of gestation before his birth. Immunisation was complete. He had been hospitalised twice previously, for early detachment and bleeding from the umbilical cord and for bleeding from the oral cavity.

Dermatological examination revealed multiple discrete to coalescing erythematous scaly plaques of various sizes, ranging from 1×1 cm to as large as 3×4 cm, were present over the trunk, extremities, buttocks, occipital scalp, and forehead [Figure 1]. A single well-defined ulcer of size 2.5×2.5 cm, with undermined edges and clean erythematous base, was present over the left upper arm at the site of the BCG injection [Figure 2]. Multiple well-defined, hyperpigmented macules were present over the trunk, right shoulder, extending towards the lower back and left thigh, suggestive of pigmentary mosaicism [Figure 1]. The infant was underweight, stunted, with gross developmental delay and microcephaly. The rest of the mucocutaneous examination was unremarkable. The patient also developed a dry cough and coryza a few days after admission, but was afebrile.

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Figure 1:

Multiple discrete erythematous to hyperpigmented scaly plaques present over the trunk along with hyperpigmented macules suggesting pigmentary mosaicism.

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Figure 2:

Single well-defined ulcer with undermined edges and erythematous base present over the upper arm.

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Laboratory investigations revealed anaemia, neutrophilia, lymphopenia, thrombocytosis, and raised erythrocyte sedimentation rate (ESR). Liver function tests were deranged, and vitamin D and serum calcium were low. Skeletal survey revealed diffuse osteopenia. Blood culture showed growth of Staphylococcus epidermidis (coagulase-negative Staphylococcus). HIV ELISA was negative. Serum immunoglobulins were decreased [S. IgA = 64.5 mg/dL, S. IgG =375.4 mg/dL] except for S. IgM (257.4 mg/dL), which was elevated. Histopathology from the ulcer showed epitheloid cells along with neutrophils, plasma cells, and a few Langerhan-type giant cells, and Ziehl Neelsen (ZN) stain was positive for acid-fast bacilli [Figures 3a and 3b]. Biopsy from the body lesions revealed features suggestive of interface dermatitis [Figure 4]. Findings from histopathology of the body lesions pointed towards the diagnosis of lichenoid dermatitis. Flow cytometry revealed a reduced B-lymphocyte count. Whole exome sequencing revealed a compound heterozygous mutation in the DCLRE1C (ARTEMIS) gene, suggestive of SCID. The patient was started prophylactically on syrup cotrimoxazole (20 mg/5 mL) 2 mL twice daily in view of immunodeficiency, along with vitamin D and calcium supplementation. Nasal saline drops were prescribed by the treating paediatrician in view of the cough. Topically, the patient was given 0.005% desonide lotion along with emollients and 2% mupirocin ointment for the ulcer. After a few days of starting treatment, the child developed aspiration pneumonia with respiratory failure and ultimately succumbed to the disease.

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Figure 3a:

Histopathology from the ulcer showed epitheloid cells along with neutrophils, plasma cells and few Langerhan type giant cells (Haematoxylin and eosin stain, 40x magnification).

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Figure 3b:

Ziehl Neelsen (ZN) stained slide from the ulcer base reveals acid fast bacilli, indicated by black arrow, at 100x magnification.

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Figure 4:

Biopsy from the erythematous scaly plaque revealed hyperkeratosis, parakeratosis, follicular plugging, irregular acanthosis. Dermis showed presence of dense inflammatory infiltrate at dermo-epidermal junction and perivascular location comprising of lymphocytes, eosinophils and few neutrophils. Focal basal cell vacuolisation with interface dermatitis along with pigment incontinence was also seen (Haematoxylin and eosin stain, 400x).

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Severe combined immunodeficiency (SCID) is a group of rare, life-threatening primary immunodeficiency disorders characterised by profound defects in both cellular and humoral immunity. Both T and B cell functions are disturbed or absent entirely in SCID. The autosomal, sporadic, or X-linked form may affect the neonate. ¹ SCID presents shortly after birth, marked by persistent infections, failure to thrive, and cutaneous lesions. Additional features include lymphadenopathy, organomegaly, eosinophilia, diarrhoea, and compromised immunity. Cutaneous lesions can present with various characteristics, such as resembling seborrheic dermatitis in colour and distribution, but are eczematous, covered by scales and crusts, particularly on the face and scalp. Lesions can manifest as erythematous macular, papular, desquamative, morbilliform, or vesiculo-papular eruptions. Alopecia is a common feature, affecting the scalp, eyelashes, and eyebrows, and in some instances, the lesions may advance to an erythroderma with progressive skin infiltration, notably on the face and skin folds of the limbs, resulting in a pachydermal appearance. ² Early recognition of skin lesions in SCID patients can lead to timely diagnosis, intervention, and management, ultimately leading to improved outcomes and potentially increasing their life expectancy. ³

This report reiterates the diagnostic significance of cutaneous manifestations as important early clues to suspect immunodeficiency, such as SCID. In this patient, a non-healing ulcer at the BCG injection site and atypical generalised eczematous lesions raised the suspicion for the underlying immunodeficiency and led to the diagnosis of SCID.