Congenital Insensitivity to Pain and Anhidrosis: Dermoscopy of a Rare Genetic Disorder

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Dear Editor, Congenital insensitivity to pain with anhidrosis (CIPA) is a remarkably rare genetic disorder characterized by the absence of pain perception and the inability to sweat.[1] It is due to a mutation affecting the Neurotrophic Tyrosine-Kinase Receptor (NTRK1) gene. Patients do not experience pain, rendering them susceptible to injuries due to the absence of protective reflexes. The clinical spectrum encompasses anhidrosis and intellectual disabilities.[2] Here, we describe a case of CIPA with its dermoscopic features and genetic study. A 5-year-old boy born out of second-degree consanguineous marriage presented with reduced sweating, parched skin, and recurrent high-grade fever since birth. Notably, fever intensified with physical exertion, particularly in hot weather. The child displayed an inability to sense pain or react to heat but remained responsive to pressure and touch. A history of recurrent biting of the tongue was present. The child had normal developmental milestones. Examination showed a few conical-shaped teeth [Figure 1a], trophic ulcers on the tongue [Figure 1b] and on the ball of the right great toe [Figure 1c]. Sparseness of hair [Figure 1d], fissures, and toe resorption [Figure 1c] were also noted. The child had fluctuating blood pressure and diminished deep tendon reflexes. Similar features were present in his maternal cousin.Figure 1: (a) Clinical image showing conical shaped teeth due to self-mutilation. (b) Trophic ulcers on the dorsum of the tongue due to self-mutilation. (c) A healed trophic ulcer with hyperkeratotic edge and resorption of the great toes. (d) Sparseness of hair on the frontal scalp with greying in a few areasLaboratory investigations revealed anemia, elevated platelet count, heightened IgE levels, and increased C-reactive protein. Magnetic resonance imaging of the brain was normal. Dermoscopy of the lower legs demonstrated a distorted pigment network, a reduction in white dots (representing eccrine openings), and preserved follicular white dots [Figure 2a]. Scales were double-edged and arranged in a net-like fashion, resembling bridal veil stinkhorn (bamboo mushroom) [Figure 2b]. Trichoscopy of the scalp revealed reduced hair density, peri- and inter-follicular scales, and hair casts [Figure 3a]. A skin biopsy from the lower leg showed a normal epidermis, absent superficial neural structures around vascular plexuses, and missing eccrine sweat glands and ducts [Figure 3b].Figure 2: (a) Dermoscopy shows furrows (black arrows) and ridges (black stars) with distorted of pigment network (black box). Note the absence of eccrine white dots with preservation of follicular white dots (yellow arrows). (Inset: clinical image of lower legs, white box indicates the site of dermoscopy). (b) Double-edged scales in furrows (black arrows) in a net like pattern, resembling veil of bamboo mushroom (inset). Note the absence of eccrine white dots in the ridges (black stars). [FotoFinder Medicam 1000, 20×, Polarised]Figure 3: (a) Trichoscopy shows sparseness of hair (maroon star), perifollicular scales (maroon arrows), and hair casts (blue circle). Note the white hairs (blue arrows). [FotoFinder Medicam 1000, 20×, Polarised]. (b) Histopathology shows normal epidermis with absence of superficial neural structures around vascular plexuses. Note the rudimentary hair follicles and absence of eccrine glands and ducts. [H and E, 100×]Genetic analysis revealed a pathogenic variant within the NTRK1 gene, situated precisely at Chr1:156834519, denoted as c.288-1G>A. This signifies an autosomal recessive inheritance and was examined at a depth of 72× during sequencing. Based on clinical features and genetic study, the diagnosis of CIPA was made. Prevalence of CIPA is 1 in 125 million newborns.[3] Diverse clinical features and paucity of facility for genetic studies are the obstacles in recognizing this condition. Typical features of CIPA, such as decreased sweating leading to hyperpyrexia, and insensitivity to pain causing recurrent skin injuries and wounds, were present. Self-mutilation of teeth and tongue resulted in broken, cone shaped teeth and trophic ulcers, respectively. Mental retardation[1] and febrile seizures[4] were absent, although they can be found in CIPA.[1,3] In CIPA, the number of sweat glands is found to be normal with absence of innervation to skin and glands.[4,5] Dermoscopy of normal skin on the lower legs shows eccrine ducts (acrosyringia) as white dots on the ridges [Figure 4a and b].[6] In this case, dermoscopy demonstrated missing eccrine white dots which correlated with absence of sweat glands in histopathology. It is possible that the lack of innervation to sweat glands results in disuse atrophy, leading to disappearance of eccrine glands. Thence, absence of white dots under dermoscopy was observed. Furthermore, absence of innervation causes parched dry skin, which was seen as scaling under dermoscopy. The scales were double-edged, prominently seen in furrows. They joined together to form a net-like appearance, resembling bridal veil stinkhorn, and correspond to hyperkeratosis. Distortion of the pigment network is probably due to atrophic rete ridges, while depigmented hair is due to decreased melanin in the hair follicles. These are preliminary findings, and further studies are required to validate them.Figure 4: (a) Clinical image of lower legs in an apparently healthy child showing dry skin. (b) Dermoscopy shows follicular white dots (black arrows), eccrine white dots (yellow arrows), and scales (yellow circles). Note the distortion of pigment network (yellow box). [FotoFinder Medicam 1000, 20×, Polarised]There are no specific guidelines for management. Parents were counseled about the nature of the disease and advised to look out for injuries, seeking appropriate advice from pediatricians, orthopedicians, and dental surgeons. It is recommended that families with CIPA should undergo prenatal screening in order to prevent the birth of another child with a similar condition. To conclude, dermoscopy in CIPA has not been described in the literature so far. Dermoscopic features were correlated well with histopathological changes. In this preliminary report, dermoscopy served as an adjunctive tool in the diagnosis of CIPA, in the context of clinical features and laboratory investigations. This case is reported because of its rarity. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.