The Dermatologist’s Guide to Systemic Clues: Highlights from the Hurwitz Lecture

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In pediatric dermatology, the connection between skin and systemic diseases is a critical area of study, with seemingly minor skin concerns posing potentially harmful systemic concerns for young patients.

At the 2024 Society for Pediatric Dermatology Annual Meeting in Toronto, ON, Lisa Weibel, MD, shared several pediatric cases of patients presenting with cutaneous manifestations of serious underlying conditions. Weibel, of Kinderspital Zürich in Switzerland, spoke to conference attendees during the first of 2 Hurwitz lectures, titled, "Skin Signs of Systemic Diseases."

Weibel’s presentation illuminated the vital role of dermatologic signs as early indicators of systemic conditions, emphasizing the importance of early recognition and intervention.

Langerhans Cell Histiocytosis and Purpuric Nail Striae

Weibel highlighted Langerhans cell histiocytosis (LCH) as a condition where dermatologic signs can be the first clue.

Purpuric nail striae, for instance, can manifest as an early symptom, guiding clinicians to investigate further for underlying LCH. This rare disease, characterized by the proliferation of Langerhans cells, can affect various organs, making early detection through skin signs crucial for comprehensive management.

GATA2 Deficiency: Warts, Hearing Loss, and Cellulitis History

In patients presenting with excessive or recalcitrant viral warts, particularly alongside hearing loss or a history of cellulitis, Weibel advised clinicians to consider GATA2 deficiency.

This genetic disorder can predispose individuals to infections and hematologic abnormalities, with skin manifestations often being the first presenting symptoms. Recognizing these signs allows for timely genetic testing and management, potentially preventing severe complications.

Infantile-Onset Autosomal Recessive Inflammatory Bowel Disease

Aphthous stomatitis, unexplained fevers, and perineal dermatitis ulcers in infants can signal infantile-onset autosomal recessive inflammatory bowel disease (IBD).

Weibel emphasized the importance of correlating these dermatologic findings with gastrointestinal symptoms to diagnose and manage this severe form of IBD effectively.

Acute Lymphoblastic Leukemia: Skin and Systemic Clues

Weibel pointed out that fever accompanied by erythematous or violaceous plaques and nodules without epidermal changes could be indicative of acute lymphoblastic leukemia. These skin signs, often overlooked, are vital for early diagnosis, allowing for prompt oncological referral and treatment initiation.

Gorlin Syndrome: Melanocytic Nevi and Milia

Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, can present with skin-tag-like melanocytic nevi and milia. Recognizing these benign skin lesions can lead to the early diagnosis of Gorlin syndrome, enabling surveillance and management to prevent the development of basal cell carcinomas and other complications.

Necrotizing Vasculitis and Levamisole Use

Purpura of the ears can be a sign of necrotizing vasculitis, often associated with the long-term use of levamisole. Weibel stressed that discontinuation of the drug typically leads to resolution, underscoring the need for drug history assessment in patients with purpura.

Congenital Syphilis and Pemphigus Syphiliticus

Pemphigus syphiliticus, a rare manifestation of congenital syphilis, was discussed as an important dermatologic clue. Early recognition and treatment of congenital syphilis can prevent severe systemic involvement and long-term morbidity.

Leigh Syndrome: Hypertrichosis and Developmental Regression

Weibel described how a panel indicating hypertrichosis along with developmental regression could lead to a diagnosis of Leigh syndrome, a severe neurological disorder. This condition, often fatal, highlights the need for a multidisciplinary approach to diagnosis and management.

Ataxia Telangiectasia: Nodules and Granulomas

Multiple asymptomatic nodules persisting for a year, combined with dermal CD8+ granulomas and a history of ataxia, can indicate ataxia telangiectasia. Weibel emphasized the importance of recognizing these signs for early diagnosis and management of this rare genetic disorder.

Hermansky-Pudlak Syndrome: Painful Nodules and Enteropathy

Painful red nodules on the legs, associated with Crohn-like enteropathy, can point to Hermansky-Pudlak syndrome, a rare form of albinism with systemic involvement. Early dermatologic recognition can facilitate appropriate genetic counseling and management.

Constitutional Mismatch Repair Deficiency: Cafe-au-Lait Macules

The appearance of café-au-lait macules, coupled with white spots and dermal melanosis, can differentiate neurofibromatosis type 1, or NF1, from constitutional mismatch repair deficiency. Early diagnosis through skin signs enables cancer surveillance and preventive measures.

Fanconi Anemia Type D1: Pigmented Macules and Cancer Risk

Typical and hypopigmented café-au-lait macules along with axillary pigmentation can indicate Fanconi anemia type D1. Weibel highlighted the importance of early diagnosis for implementing cancer surveillance programs, given the high risk for solid tumors in these patients.

Conclusions

Weibel concluded her lecture by stressing the critical role of dermatologists in recognizing skin signs as early identifiers of systemic diseases. Early diagnosis through these dermatologic clues can lead to timely interventions, significantly improving patient outcomes.

"It's really important that we as pediatric dermatologists diagnose these especially significant issues in order for them to get appropriate treatment from colleagues in other specialties," Weibel concluded.

Reference

Weibel L. Hurwitz lecture part 1: Skin signs of systemic diseases. Presented at the 2024 Society for Pediatric Dermatology Annual Meeting, July 11-14; Toronto, ON.