Silvery Hair with Speckled Dyspigmentation: Chediak-Higashi Syndrome in Three Indian Siblings.

Silvery hair is a common feature of Chediak-Higashi syndrome (CHS), Griscelli syndrome, and Elejalde syndrome. CHS is a rare autosomal recessive disorder characterized by partial oculocutaneous albinism, frequent pyogenic infections, and the presence of abnormal large granules in leukocytes and other granule containing cells. A 6-year-old girl had recurrent respiratory infections, speckled hypo- and hyper-pigmentation over exposed areas, and silvery hair since early childhood. Clinical features, laboratory investigations, hair microscopy, and skin biopsy findings were consistent with CHS. Her younger sisters aged 4 and 2 years had similar clinical, peripheral blood picture, and hair microscopy findings consistent with CHS. This case is reported for its rare occurrence in all the three siblings of the family, prominent pigmentary changes, and absent accelerated phase till date. Awareness, early recognition, and management of the condition may prevent the preterm morbidity associated.

INTRODUCTION

Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive, immunodeficiency disorder, exhibiting partial albinism with silvery grey hair, photosensitivity, pyoderma, hyperhidrosis, and easy bruisability.[1] It constitutes a part of the “silvery hair syndrome” in association with Griscelli syndrome and Elejalde syndrome.[2] We report this rare disorder in three sisters of a single family.

CASE REPORT

A 6-year-old girl, born to consanguineous parents, had asymptomatic pigmentary lesions over face and upper extremities for 4 years. She had recurrent respiratory infections and variable hair color since early childhood. There was no spontaneous bleeding, photophobia, or systemic involvement. Her developmental milestones and vaccination status were up to date. Her younger sisters aged 4 and 2 years had almost similar features. Both her parents were unaffected.

Cutaneous examination showed speckled hypo-and hyperpigmented macules over the malar region, nose, and freckles over extensor forearms. Silvery-grey hair over frontal scalp, eyebrows, eyelashes [Figure 1], and ocular pigmentary dilution was present. Other systems including neurological findings were normal. Her sisters also had silvery-grey hair with freckling over the face [Figure 2]. Her hematological, biochemical, and tests for infections including tuberculosis were normal or negative except for neutropenia. Peripheral smear showed giant cytoplasmic granules in the leucocytes. Light microscopy of scalp hair showed evenly distributed melanin granules of a regular diameter which were bigger than those seen in normal hair [Figure 3]. Skin biopsy from face showed scattered, large, coarsely pigmented melanocytes in the epidermis with the sparse pigmentation of adjacent keratinocytes accompanied by pigmented cells in the superficial dermis [Figure 4]. Bone marrow examination was refused by the parents and genetic tests could not be done for the want of facilities. Light microscopy of scalp hair and a peripheral smear of both her sisters’ showed similar features. With these clinical and laboratory findings, a diagnosis of CHS was made and patients were referred for bone marrow transplantation (BMT).

Figure 1

Speckled hypo-and hyper-pigmentation over face with silvery hair over scalp and eyebrows

Figure 2

Involvement in both the sisters

Figure 3

Light microscopy of hair mount with large aggregates of pigment granules distributed regularly (×450)

Figure 4

Histopathological examination showing large, coarse, pigmented melanocytes in the epidermis (H and E, ×200)

DISCUSSION

Chediak-Higashi syndrome, first described in 1943, results from a mutation in CHS1 gene located on chromosome 1q 42–43 leading to abnormal intracellular protein transport.[34] Defective melanization of melanosomes results in oculocutaneous albinism. It affects all races with equal sex distribution. The symptoms usually appear soon after birth or in early childhood. Apart from cutaneous and neurological involvement, lymphadenopathy, aphthae, gingivitis, jaundice, recurrent sinopulmonary infections, and fever may be seen.[4] Our patients had recurrent respiratory infections without involving other systems.

Occasionally, speckled hypo-pigmentation and hyper-pigmentation on sun-exposed areas similar to our case is reported to occur in Japanese and Saudi children.[3] This may be due to a defect in the degradation of melanosomes or melanosome complexes along with an increase in the tyrosinase activity in dark skinned populations in response to repeated sun exposure.[3]

In majority (85%) of cases, accelerated phase, characterized by fever, jaundice, lymphoreticular, and neurologic involvement with eventual death are noted. Epstein–Barr virus has been implicated as a precipitating factor. Based on the clinical and investigational findings, a diagnosis of CHS without accelerated phase was made in our patients. Differential diagnoses with salient features are highlighted in Table 1. It is important to differentiate, as the prognosis and treatment varies.[25] Prenatal diagnosis can be done using fetal hair or white blood cells.[4]

Table 1

Summary of differential features for silvery hair syndrome

Treatment options are limited and the only definitive treatment is BMT from a human leukocyte antigen-matched donor.[6] Infections are treated with antibiotics. High dose Vitamin C and granulocyte colony stimulating factor therapy may improve immune function and clotting.[4] In the accelerated phase, etoposide, steroids, methotrexate, cyclophosphamide, and acyclovir are tried. Survival into adulthood without accelerated phase is seen in up to 15% of cases. Early death in CHS occurs due to infection or bone marrow failure. The prognosis is good if BMT is done before the setting in of accelerated phase.

Financial support and sponsorship

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Conflicts of interest

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