Co-occurrence of Griscelli Syndrome Type 2 and Systemic Juvenile Idiopathic Arthritis in a Pediatric Patient: A Case Report

Introduction

Griscelli syndrome type 2 (GS2) is a rare, autosomal recessive inherited immune disorder, phenotypically characterized by partial albinism and immunodeficiency. GS2 results from mutations in the RAB27A gene, which encodes a GTPase crucial for intracellular protein transport and cytotoxic function. These mutations cause immunodeficiency and increase susceptibility to hemophagocytic lymphohistiocytosis (HLH).^1,2

sJIA is an autoinflammatory condition characterized by quotidian fevers, transient evanescent rash, arthritis, lymphadenopathy, and hepatosplenomegaly. Systemic JIA can be associated with macrophage activation syndrome (MAS), a severe complication considered a form of secondary HLH. ³

The overlapping clinical features of MAS-HLH present diagnostic challenges.

This report describes a pediatric patient with systemic inflammatory symptoms mimicking sJIA, who was later diagnosed with GS2 through genetic testing. The case highlights the importance of evaluating patients with atypical or treatment-resistant inflammatory presentations for underlying immunodeficiencies.

Case Report

An 18-month-old female child, born to non-consanguineous parents with no prior medical history, presented with a 2-week history of daily spiking fevers and a salmon-pink rash that appeared with the fever spikes (Figure 1A). She had silvery hair since birth (Figure 1B). She had received no prior medications. On examination, she was febrile and toxic appearing. She had bilateral cervical lymphadenopathy. Arthritis was noted in the bilateral knees and ankles. No organomegaly was detected.

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Figure 1.

(A) Evanescent salmon-pink maculopapular rash on the trunk during febrile episodes. (B) Silvery hair and hypopigmented skin in an 18-month-old girl diagnosed with Griscelli syndrome type 2.

Vital signs: temperature 38°C, heart rate 122 bpm, respiratory rate 22/min. Initial laboratory investigations revealed leukocytosis, anemia, thrombocytosis (Platelets 565 × 10⁹/l; normal 100-400) and markedly elevated inflammatory markers, including Erythrocyte Sedimentation Rate 140 mm/h (normal 1-20), C-Reactive Protein (CRP) 176 mg/l (normal < 5), and ferritin > 2000 ng/ml (normal 10-140) with normal levels of fibrinogen and triglycerides (see Table 1 for the full work-up).

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Table 1.

Clinical and Laboratory Findings of the Pediatric Patient With Co-occurring GS2 and sJIA, Including Exclusion of Infectious, Autoimmune, and Malignant Causes.

Parameter	Result	Reference range/Notes
Clinical features
Quotidian fever	+	—
Evanescent erythematous rash	+	—
Lymphadenopathy	Bilateral cervical LAP	—
HSM	−	—
Serositis	−	—
Arthritis	+	—
Laboratory investigations
White blood cells (WBC) (×109/l)	21.2	3.5-10.0
Granulocytes% (×109/l)	83.7	35.0-80.0
Lymphocytes% (×109/l)	14.3	15.0-50.0
Hemoglobin (g/dl)	10.9	11.5-16.5
PLT (×109/l)	565	100-400
ESR (mm/1 h)	140	1-20
CRP (mg/l)	176	<5
Ferritin (ng/ml)	>2000	10.0-140.0
Alanine Aminotransferase (U/l)	32.8	0.0-45.0
Aspartate Aminotransferase (U/l)	61.7	0.0-40.0
Alkaline Phosphatase (U/l)	207	53-128
Total bilirubin (mg/dl)	0.25	0.30-1.20
Albumin (g/dl)	3.65	3.50-5.20
Fibrinogen (g/dl)	2.3	2.0-4.0
Serum triglycerides (mg/dl)	94.72	<150
Exclusion of other causes
General Urine Examination	Normal	—
Typhoid serology	Negative	—
Abdominal U/S	Normal	—
Chest X-Ray	Normal	—
Cerebrospinal Fluid analysis	Normal	—
Anti–Cyclic Citrullinated Peptide (U/ml)	<20	—
Antinuclear Antibodies (RU/ml)	<2.00	—
Anti-ds DNA IgG (RU/ml)	<2.00	—

The peripheral blood smear showed normocytic anemia. Bone marrow aspiration revealed normal cellularity without blasts or hemophagocytosis.

Hair shaft microscopy raised suspicion for Griscelli syndrome.

Given the suspected diagnosis of Griscelli syndrome and known association with HLH, this was the primary consideration in the differential diagnosis due to fevers and hyperferritinemia. However, the diagnostic criteria for HLH were not met, as there was no evidence of cytopenias, hypofibrinogenemia, hypertriglyceridemia, or hemophagocytosis. Blood cultures grew coagulase-negative Staphylococcus, which was considered a contaminant. Nevertheless, as the patient remained febrile and was hospitalized for 4 weeks, empiric and prophylactic antibiotic therapy, including Vancomycin (1 g BID), was initiated to manage potential infection and prevent nosocomial complications. Due to the ongoing fevers, evanescent rash, and arthritis, the possibility of systemic JIA was considered. This diagnosis was supported by her clinical characteristics, elevated inflammatory markers, and the exclusion of infectious, malignant, and autoimmune causes per Table 1. Subsequent RAB27A gene sequencing confirmed the diagnosis of Griscelli syndrome type 2. There was no clinical or laboratory evidence of rheumatic fever, and the virology screen for CMV and EBV was unremarkable. The patient also had no clinical manifestations suggestive of Kawasaki disease, as there were no ocular or cutaneous–mucosal findings, and the echocardiographic study was normal. Regarding biomarkers such as CD25 or interleukin (IL)-18, these tests are unfortunately not available in our country. HLH was excluded based on the absence of cytopenias, the persistent fall in ESR, and the normal fibrinogen level. The combination of clinical and laboratory findings ultimately led to a final diagnosis of sJIA with underlying GS2. Oral prednisolone (2 mg/kg/day) was initiated for 1 month and gradually tapered. The patient’s fever, rash, and inflammatory markers improved, and she remained in remission (Figure 2).

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Figure 2.

Clinical image of the patient after treatment showing resolution of rash, improved overall condition, and sustained remission following corticosteroid therapy.

Discussion

sJIA is a distinct subtype of juvenile idiopathic arthritis that commonly presents with quotidian fevers, evanescent rash, arthritis, lymphadenopathy, hepatosplenomagly, and serositis. Diagnosing sJIA involves the careful exclusion of infectious, malignant, autoimmune, and other inflammatory disorders. ⁴

In our case, the diagnosis of Griscelli syndrome added complexity due to its association with an increased risk of developing primary HLH. Because of the clinical and laboratory overlap between primary HLH and sJIA, a thorough evaluation was necessary. HLH was initially suspected but ultimately ruled out, as the HLH-2004 diagnostic criteria were not fulfilled.

sJIA itself is associated with an elevated risk for MAS, a form of secondary HLH. Approximately 10% of patients with sJIA may develop overt MAS, typically during active phases of the disease. ⁵

In this case, hyperferritinemia and systemic inflammation prompted close monitoring for MAS, especially following the diagnosis of Griscelli syndrome. Nevertheless, the patient’s condition remained clinically stable, with no progression to MAS-HLH, and she responded well to corticosteroid treatment alone.

To date, medical literature offers limited to no evidence of a recognized association between GS2 and sJIA. Griscelli syndrome results from immune dysregulation linked to mutations in the RAB27A gene. This gene encodes a protein vital for melanosome trafficking within melanocytes and the exocytosis of granules from cytotoxic T lymphocytes, neutrophils, and natural killer cells. This underlies the characteristic features of hypopigmentation and immunodeficiency. ⁶

sJIA is driven by innate immune system dysfunction and cytokine dysregulation, involving molecules such as IL-1, IL-6, and interferon-gamma. ³ Although these 2 diseases originate from distinct immunological mechanisms, the co-occurrence in this patient suggests a shared underlying predisposition to dysregulated immune activation. This observation also raises the possibility that having an immune deficiency disorder such as Griscelli syndrome may predispose a patient to developing—or modifying the course of—autoinflammatory diseases like sJIA. The patient will require close monitoring during future sJIA flares, given her predisposition to HLH.