Histiocytoses constitute a group of proliferative disorders of bone marrow origin. Currently, they are classified into 5 main groups based on their clinical, histological, and molecular characteristics. Within group C (cutaneous and mucocutaneous histiocytoses), generalized eruptive histiocytosis (GEH) is included, a very rare disorder, especially in childhood.1

A 9-year-old girl presented with a 1-year history of pruritic skin lesions. The lesions appeared in an eruptive manner weeks after administration of the meningococcal B vaccine. On physical examination, she exhibited monomorphic erythematous-brown macules measuring 3–7mm in diameter, distributed in a generalized pattern, more abundant on the extremities and less numerous on the trunk and face. Some lesions on the legs were papular and more yellowish in color (Fig. 1). No lymphadenopathy or visceromegaly was detected.

Fig. 1.

Cutaneous lesions consisting of erythematous-brown macules affecting the trunk and upper (A) and lower (B) extremities.

Multiple skin biopsies were obtained from different sites and at different time points, with similar results (Fig. 2). Histopathologic examination revealed an interstitial infiltrate of histiocytes with foamy cytoplasm and occasional multinucleated Touton-type giant cells. The histiocytic nature of the infiltrate was confirmed by positivity for CD68 and CD163. CD1a and S100 markers were negative. Based on the histological findings and clinical presentation, a diagnosis of non-Langerhans cell histiocytosis consistent with GEH was established.

Fig. 2.

(A) Initial skin biopsy showing an infiltrate in the superficial and mid dermis composed of histiocyte-like cells (H&E, 200×). (B) At higher magnification, cells exhibit foamy cytoplasm with a rounded nucleus and occasional multinucleation (H&E, 600×). These cells are positive for CD163 (C, 200×) and CD68 (D, 200×), and negative for S100 (E, 200×) and CD1a (F, 200×).

In GEH, crops of monomorphic lesions typically appear with generalized distribution but without involvement of other organs. It has been hypothesized that GEH represents an early and indeterminate stage of other histiocytoses within group C, which are more persistent and may exhibit extracutaneous involvement, such as disseminated xanthogranuloma, disseminated xanthoma, or progressive nodular histiocytosis, suggesting a spectrum rather than distinct entities.2

To date, a total of 79 cases of GEH have been reported, 24 (30%) of which have been described in children.3 Most cases resolved within 2 years; however, progression to disseminated xanthoma has been described in 3 patients. Therefore, although GEH is traditionally considered a self-limited condition and management is usually conservative, close follow-up is recommended to detect possible systemic involvement. In our patient, abdominal ultrasound, blood tests, complete skeletal survey, and ophthalmologic evaluation were performed, all with normal results. After 2 years of follow-up, she was diagnosed with autoimmune thyroiditis and started on levothyroxine replacement therapy.

The development of concomitant autoimmune disease is common in multicentric reticulohistiocytosis but not in GEH or other histiocytoses within the juvenile xanthogranuloma spectrum.1

Regarding the vaccination history in our case, only one case of hemophagocytic lymphohistiocytosis following SARS-CoV-2 vaccination has been reported.4

The skin lesions remained stable from diagnosis, with occasional exacerbations associated with upper respiratory infections. It was noted that during the summer months, lesions improved in sun-exposed areas, along with a reduction in pruritus. Based on this observation, phototherapy was initiated, as previous treatments (topical corticosteroids and immunomodulators) had been ineffective.

Narrowband UVB phototherapy was administered, with a total of 19 sessions and a cumulative dose of 9720mJ/cm2. Treatment resulted in a significant reduction in pruritus and improvement in lesion appearance. Two years after treatment, the patient still had residual lesions, but these were asymptomatic.

There is no standardized treatment for group C histiocytoses, as none of the available therapies (corticosteroids, isotretinoin, immunosuppressants) have demonstrated superiority.3 Given the tendency toward spontaneous resolution, watchful waiting is also an option. In our case, the improvement observed during summer months supported the use of phototherapy.

Most experience in cutaneous histiocytoses involves PUVA phototherapy, with 2 reported cases of GEH in adults treated with this modality; however, it is not recommended in children.5,6

Narrowband UVB phototherapy may represent a safe and effective alternative. To date, only 4 cases of group C histiocytoses treated with this modality have been reported, 3 with narrowband UVB and 1 with broadband UVB, with only 1 pediatric case.7–10

In conclusion, we report a new pediatric case of GEH with a persistent course, possibly triggered by meningococcal B vaccination and associated with subsequent development of autoimmune disease, with no previously reported similar cases.

We highlight the use of narrowband UVB phototherapy in the treatment of this type of histiocytosis. Although its efficacy is moderate, similar to other available treatments, its low risk of adverse effects makes it a safe and widely accessible option in most centers.