THE PHENOMENON OF HALO-LIKE DISAPPEARANCE OF THE MONGOLIAN SPOT ON LESIONS COMBINED WITH CAFÉ AU LAIT SPOT OR ACQUIRED PIGMENTED NEVUS

When café au lait spots or pigmented nevi were combined with Mongolian spot lesions, whitish haloes were observed in the areas surrounding these café au lait spots and pigmented nevi. The pathogenesis of this halo-like phenomenon was investigated. The materials were two Japanese girls who had Mongolian spots present at birth over the sacrum and buttocks. In case 1, an eight-month-old, café au lait spots and in case 2, a six-month-old, brownish black pigmented spots appeared about one month after birth and gradually increased in size and number on the trunk and extremities. In the café au lait spot and pigmented nevus (histologically compound type) lesions and their boundary areas, a whitish halo-like zone, dermal melanocytes were small and round, as compared with those of surrounding Mongolian spots, although only slightly decreased in number. The characteristic bipolar dendrites were almost imperceptible. The dopa reaction of dermal melanocytes was also decreased. In the boundary halo-like areas in both cases, epidermal melanin granules and dopa-positive melanocytes were almost identical to those of the surrounding Mongolian spot. Mongolian spots were already present at birth in both cases, but the café au lait spots and pigmented nevi definitely appeared to arise on these Mongolian spot after birth. The Mongolian spots seemed to disappear at the sites of café au lait spots, pigmented nevi and boundary areas, perhaps a kind of Sutton's phenomenon.     

Vitamin D3 analogues improve café au lait spots in patients with von Recklinghausen's disease: experimental and clinical studies

Topical application of vitamin D3 analogues for 6 months was found to be effective in improving the pigmentation of café au lait spots in patients with von Recklinghausen's disease. Treatment of café au lait spots grafted onto nude mice with a vitamin D3 analogue caused suppression of bromodeoxy- uridine uptake in the cells of the basal layer. Vitamin D3 analogues also decreased melanin pigment in café au lait spots after 4 weeks of treatment. Thus, it is considered that long-term application of vitamin D3 analogues is effective both for improving the pigmentation of café au lait spots and suppressing the development of neurofibromas in patients with von Recklinghausen's disease.     

Halolike Phenomenon Around a Café au Lait Spot Superimposed on a Mongolian Spot

An 8‐month‐old Caucasian infant with neurofibromatosis type 1 presented with a congenital plexiform neurofibroma and multiple café au lait spots. A pale area surrounded one of the café au lait spots located on the left gluteus in the area of dermal melanocytosis. This halolike phenomenon results from the disappearance of the Mongolian spot around the café au lait spots, revealing normal pigmented skin. This sign has been described rarely in the literature and the pathogenic mechanism is unclear.     

Pigmentary Anomalies in the Multiple Lentigines Syndrome: Is it Distinct from LEOPARD Syndrome?

Abstract: We observed 2 families with 26 individuals affected by multiple lentigines syndrome (MLS). All patients had extensive generalized lentigines, including in the axillary and inguinal regions, diffuse hyperpigmentation, hypopigmented patches, and hyperpigmented patches, many of which appeared clinically to be café au lait spots. Multiple lentigines syndrome should be considered in the differential diagnosis of multiple café au lait spots in children, particularly since the spots are usually present before the lentigines develop and may be clinically indistinguishable from the café au lait spots of neurofibromatosis. No significant non-cutaneous features occurred in the two families with three generations of affected individuals, suggesting that MLS is a distinct entity. However, patients with the noncutaneous abnormalities of the LEOPARD syndrome have been described in families in which most members had pigmentary lesions only. Therefore, patients with multiple lentigines should be evaluated for noncutaneous abnormalities, particularly hearing loss and cardiac anomalies. Similarly, until investigators demonstrate lack of genetic linkage between MLS and LEOPARD syndrome, genetic counseling of patients affected by the cutaneous features of the former should include the potential for noncutaneous features in offspring.     

Café au lait spots: When and how to pursue their genetic origins

Café au lait spots are common birthmarks seen sporadically and in association with several genetic syndromes. Dermatologists are often asked to evaluate these birthmarks both by other physicians and by parents. In some cases, it is challenging to know when and how to pursue further evaluation. Diagnostic challenges may come in the form of the appearance of the individual lesions, areas and patterns of cutaneous involvement, and associated features (or lack thereof). In this review, we aim to clarify when and how to evaluate the child with multiple or patterned café au lait spots and to explain some emerging concepts in our understanding of the genetics of these lesions.     

Association of Piebaldism,Multiple Café‐au‐lait Macules,and Intertriginous Freckling: Clinical Evidence of a Common Pathway between KIT and Sprouty‐Related,Ena/Vasodilator‐Stimulated Phosphoprotein Homology‐1 Domain Containing Protein 1 (SPRED1)

Abstract: Piebaldism is a rare genodermatosis caused by KIT mutations. We report the case of a 5‐year‐old boy who had the white forelock and leukoderma of piebaldism, but the presence of many café‐au‐lait macules and axillary and inguinal freckling complicated the diagnosis. Patients with similar cutaneous findings have been previously reported, and their disorder has been attributed to an overlap of piebaldism and neurofibromatosis type 1. Legius syndrome is a recently described syndrome caused by Sprouty‐related, Ena/vasodilator‐stimulated phosphoprotein homology‐1 domain containing protein 1 (SPRED1) mutations that also has multiple café‐au‐lait macules and intertriginous freckling. Based on our current understanding of KIT and SPRED1 protein interactions, we propose that café‐au‐lait macules and freckling may be seen in some patients with piebaldism and does not necessarily represent coexistence of neurofibromatosis type 1.     

Association of piebaldism and neurofibromatosis type 1 in a girl

We report an 11-year-old girl with both piebaldism and neurofibromatosis type 1 (NF1). The patient had large depigmented patches on her lower limbs and a white forelock since birth. In addition, some café au lait spots were present on her trunk at birth and had increased in number and size during childhood in concomitance with the appearance of axillary and inguinal freckling. Neither neurofibromas nor Lisch nodules were detected and the patient was otherwise healthy. Pedigree analysis revealed inheritance for piebaldism on the paternal side. To our knowledge, the association of piebaldism and NF1 has been described previously in only three patients. Awareness of this rare association is relevant to ensure early diagnosis and adequate follow-up for NF1.     

Diagnostic value of multiple café‐au‐lait macules for neurofibromatosis 1 in Chinese children

Neurofibromatosis 1 (NF1) is a common autosomal dominant condition caused by mutations in the NF1 gene. The appearance of multiple café‐au‐lait macules is an early sign of the condition, which often alert physicians to follow up and further examine the patient for the possibility of NF1. In order to determine the predictive value of multiple café‐au‐lait macules at early age for NF1 in Chinese patients, we recruited 19 children who shared the common sign of multiple café‐au‐lait macules from a general pediatric clinic in Shanghai. All the patients were clinically evaluated following the National Institutes of Health criteria for NF1 and molecular tested for sequence variants and copy number changes. Nine children met the clinical diagnostic criteria of NF1, and molecular tests confirmed all nine patients with pathogenic variants including two genomic deletions, two novel frame‐shift variants, four novel nonsense and a splicing variants. In addition, four children who did not meet the diagnostic criteria were also found to carry pathogenic NF1 variants. Overall, 68.4% (13/19) of children with café‐au‐lait macules and various other clinical presentations were molecularly confirmed with NF1. This study demonstrated that the majority of Chinese children with multiple café‐au‐lait macules who came to seek for medical attention had NF1. Molecular testing is necessary to be used as an adjunct and sometimes as the main tool for confirming and diagnosing children of NF1 at early age.     

The Russell-Silver syndrome: a case report and brief review of the literature

The Russell-Silver syndrome's phenotypic features consist of musculoskeletal abnormalities, genitourinary malformations, craniofacial dysmorphy and cutaneous dyschromia, which is usually reported as café au lait spots. We present the first instances of a large, unilateral, achromic patch as an additional cutaneous manifestation of the Russell-Silver syndrome.     

Ultrasound as a Diagnostic Aid in Identifying Neurofibromas

Neurofibromatosis 1 is a multisystem disorder associated with substantial clinical variability. During childhood, few neurofibromas and café au lait spots may be the only manifest symptoms, making correct and timely diagnosis difficult. Herein we describe the clinical usefulness of ultrasound examination in identifying neurofibromas.     

Café au lait macules and juvénile polyps

Abstract: Several hereditary and nonhereditary gastrointestinal tract polyposis syndromes exhibit extra‐intestinal manifestations, including cutaneous findings. However, a lack of information exists regarding cutaneous features of juvenile polyposis. Our objective was to document the prevalence of cutaneous hyperpigmented lesions in children with juvenile polyposis coli or juvenile polyposis coli and their first degree relatives. Children seen in the gastroenterology practice at The Children's Hospital in Denver, Colorado with polyps (juvenile polyposis coli, sporadic juvenile polyps, and familial adenomatous polyposis coli) and their first degree relatives were invited to participate in the study. A comprehensive skin examination was performed on those who consented to participate. We found that 8 of 14 patients (eight with juvenile polyposis coli, four with juvenile polyposis, and two with familial adenomatous polyposis coli) had at least one café‐au‐lait macule, compared with three of 27 relatives (p = 0.003). The prevalence of at least one café‐au‐lait macule in our patients (8/14 or 57.1%, CI: 28.9–82.3%) was significantly higher than the general population prevalence of 28.5% (p = 0.023). However, if the two patients with familial adenomatous polyposis coli were excluded, the comparison with the general population prevalence did not reach statistical significance (p = 0.095). The prevalence of multiple café‐au‐lait macules in our patients (4/14 or 28.6%; CI: 8.4–58.1%) was significantly higher than the general population prevalence of 5.2% (p = 0.005). A notable finding was the presence of multiple café‐au‐lait macules in 4 of 12 juvenile polyposis coli/juvenile polyposis patients. Two patients with juvenile polyposis coli also had lentigines. In this selected case series, we observed single or multiple café‐au‐lait macules in a high proportion of children with the three types of polyps. Further studies are needed to assess a possible common pathway for hamartomatous polyps and café‐au‐lait macules.     

Large solitary café au lait spots: a report of 5 cases and review of the literature

The presence of multiple café au lait spots (CALSs) has been well described and associated with several neurocutaneous and genetic syndromes including, most commonly, neurofibromatosis. However, scant literature exists regarding the clinical significance of the large solitary CALS. We describe 5 patients with congenital large solitary CALSs without associated abnormalities. Our cases and review of the literature suggest that large solitary CALSs are uncommon benign lesions that most likely are not associated with any neurocutaneous syndromes or developmental anomalies.     

Confocal laser scanning microscopy‐guided su rgery for neurofibroma

The neurofibromatoses comprise at least two separate genetic disorders with variable clinical features and an unpredictable course. The most common type, neurofibromatosis 1, is characterized by ≥ 6 café‐au‐lait spots and the occurrence of neurofibromas, which may present as cutaneous, subcutaneous or plexiform lesions. Normally, excision of neurofibromas is only indicated in the presence of neurological symptoms, suspicion of malignancy or for exceptional cosmetic reasons. For a good functional and aesthetic result with the least danger of recurrence, the surgeon’s goal is to excise as much tissue as necessary and as little tissue as possible. One of the main issues during the surgical procedure is to distinguish between neurofibroma and surrounding tissue. We report for the first time the use of confocal laser scanning microscopy to differentiate between neurofibroma and healthy skin.     

Juvenile xanthogranuloma associated with neurofibromatosis 1: 14 patients without evidence of hematologic malignancies

The clinical features and natural history of juvenile xanthogranuloma (JXG) in 14 children affected by neurofibromatosis 1 (NF1) are reported. Mean follow-up in 11 of these patients was 4.3 years (range 1-10 years). None of the children developed hematologic malignancies during this period. The onset of JXG was in the first 2 years of life in 13 of the patients. In this series, the association between JXG and six or more café au lait spots more than 5 mm in diameter was a good marker for NF1 in the first few years of life. Overall the JXG in these patients did not show any features distinguishable from those of "classical" JXG.     

Atypical naevus spilus: detection by in vivo confocal microscopy

Naevus spilus (NS) is a naevoid disorder characterized by hyperpigmented macules or papules scattered over a café‐au‐lait macule. Such café‐au‐lait macules are often present at birth, and the darker pigmented speckles of NS slowly increase in number and size over a period of several years. NS can therefore be difficult to evaluate clinically for the development of melanoma. In vivo confocal microscopy (IVCM) is a novel method that allows examination at cellular resolution of cutaneous lesions in vivo. IVCM has been shown to have twice the specificity of dermoscopy for the diagnosis of melanoma, with comparable sensitivity. It has been shown to be useful in the detection and grading of dysplastic naevi, which are recognized precursors of melanoma in some cases. In this report, we highlight that IVCM can also be used as a tool complementary to dermoscopy to identify areas of dynamic change in clinically and dermoscopically equivocal lesions. IVCM may thereby assist in the early detection of melanocytic atypia and melanoma arising in NS, in turn leading to excision of melanoma at an early stage, which is associated with a favourable outcome. We also outline some of the difficulties encountered in confocal microscopy and histology when differentiating melanoma from dysplastic naevi.     

Papel de la resonancia magnética en niños con hemangiomas lumbosacros y perineales: informe de 3 casos clínicos y revisión de la literatura

Cutaneous hemangiomas are the most frequent benign tumors in children. When they affect the lumbar and perineal area some cases can be associated with an occult spinal dysraphism. The management of these hemangiomas lack consensus. We report 3 cases of children with lumbosacral and perineal hemangiomas with magnetic resonance image abnormalities and we review the literature to find out the type and timing of tests that should be performed to complete the study in these patients. Ultrasound is typically requested as young as possible, as this imaging technique is not possible 11 the posterior spinal elements have ossified. MRI is the gold standard for diagnosing occult spinal dysraphism. According to the literature, the mean age for MRI screening should be around 6 months, when the fat formation in the filum terminale is expanded. In our opinion, an MRI scan should be performed at 6 months of age in every children with lumbar or perineal hemangioma regardless the lesion size, neurological symptoms or the ultrasound results.     

Halo naevi and café au lait macule regression in a renal transplant patient on immunosuppression

A case of halo naevi and café au lait macule regression in a renal transplant patient receiving long‐term immunosuppressive therapy is described. We propose the direct transfer of an auto‐reactive antibody, CD8 T‐cells or tumour necrosis factor α from the transplant donor to the recipient as a possible cause. We have also considered insufficient immunosuppressive therapy as a possible mechanism.     

Classification and prevalence of pigmented lesions in patients with total-body photographs at high risk of developing melanoma

BACKGROUND: The classification of many pigmented lesions is not well defined, and an association with melanoma has not been established. OBJECTIVE: To better define the spectrum of pigmented lesions (excluding common and dysplastic nevi) and explore links to melanoma. METHODS: Retrospective review of patients with total-body digital photographs at high risk of developing melanoma from the Memorial Sloan-Kettering Cancer Center Dermatology Service. RESULTS: Among 598 patients, 7.7% had café au lait spots, 2.8% had nevi spilus, 2.3% had congenital nevus-like nevi, 2% had "other" lesions, 1.2% had segmental speckled lentiginous nevi, and 1% had agminated nevi. There was no statistical difference in the prevalence rates of these pigmented lesions in patients with or without a history of melanoma or >or= 100 nevi. CONCLUSIONS: A wide range of pigmented lesions require further classification and study to explore possible links to melanoma.     

Sudden Onset Vision Loss in an 8‐year‐old Female with McCune–Albright Syndrome

Abstract: We describe a case of an 8‐year‐old girl with large irregular café au lait macules on the right cheek and right lower extremity presenting with sudden onset vision loss and found to have polyostotic fibrous dysplasia on imaging. The classic triad of McCune–Albright syndrome is discussed along with the importance of recognition in patients with partial presentation. This case also highlights a rare and potentially devastating neurologic complication of McCune–Albright syndrome, as well as the need for early diagnosis and continual surveillance in these patients.     

Statistical Survey of Skin Changes in Japanese Neonates

We observed 5387 infants over 10 years in weekly visits to a neonatal ward and obtained the following frequency data on these skin changes: erythema toxicum neonatorum, 40.8%; perianal dermatitis, 18.9%; scrotal pigmentation, 15.2%; miliaria, 8.5%; and adnexal polyp of neonatal skin, 4.1%. The frequencies of the types of birthmarks were: mongolian spots, 81.5%; salmon patches, 22.3%; nevocellular nevi, 2.7%; port-wine stains, 2.1%; strawberry marks, 1.7%; café au lait spots, 1.7% (including a case of von Recklinghausen's disease); epidermal and sebaceous nevi, 0.3%; accessory auricles, 0.3%; and smooth muscle hamartomas, 0.2%. A positive relationship was observed between infant maturity and the prevalence of erythema toxicum neonatorum. Apart from candidiasis, neonatal skin infections were extremely rare.