Complications in patients with congenital insensitivity to pain and anhidrosis: a systematic review

Abstract

Background. Congenital Insensitivity to Pain and Anhidrosis (CIPA) is a rare hereditary sensory and autonomic neuropathy type IV (HSAN IV) caused by NTRK1 gene mutations. It disrupts pain and temperature regulation, leading to anhidrosis, recurrent fever, self-injury, and, in severe cases, intellectual disability. The absence of pain perception increases the risk of unnoticed injuries and long-term complications. Understanding these complications is essential to improving patient care and quality of life.

Methodology:  A systematic search on PubMed, ScienceDirect, and ProQuest was conducted on October 30, 2024, using keywords related to CIPA and HSAN IV. This review included English-language clinical studies and case reports (2014–2024) reporting complications of CIPA. Reviews, books, inaccessible articles, and duplicates were excluded. A total of 29 case reports were analyzed, with quality assessed using JBI Critical Appraisal Tools.

Result. A total of 29 articles met the inclusion criteria, reporting complications among patients with CIPA. The most frequently observed complications were fever (87%), self-mutilation (73%), and recurrent fractures (68%), while developmental delay (63%) represented a major neurodevelopmental manifestation. The mean age of patients was 10.9 years, ranging from 1 to 38 years. Most reported cases originated from China (41%).

Conclusion. This review emphasizes the importance of early diagnosis in CIPA patients to prevent complications. However, current studies often lack comprehensive follow-up, which hinders our understanding of long-term outcomes. Further research is needed to fill these gaps and improve the quality of life for patients with this rare condition.

Abbreviations: CIPA: Congenital Insensitivity to Pain and Anhidrosis, HSAN IV: hereditary sensory and autonomic neuropathy type IV, NTRKI: neurotrophic tyrosine kinase 1,

Keywords: Congenital insensitivity to pain and anhidrosis, hereditary sensory and autonomic neuropathy type IV

Citation: Rini PN, Irvandy MS, Pradhea TA. Complications in patients with congenital insensitivity to pain and anhidrosis: a systematic review. Anaesth. pain intensive care 2025;29(6):1290-1301. DOI: 10.35975/apic.v29i6.3067

Received: February 16, 2025; Revised: November 02, 2025; Accepted: November 16, 2025