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Year : 2014  |  Volume : 15  |  Issue : 2  |  Page : 79-82

Anhidrosis and nonhealing painless leg ulcer with osteomyelitis in a young boy

1 Department of Pediatric Medicine, R G Kar Medical College, Kolkata, West Bengal, India
2 Department of Dermatology, Venereology, and Leprosy, R G Kar Medical College, Kolkata, West Bengal, India

Date of Web Publication27-Aug-2014

Correspondence Address:
Sudip Kumar Ghosh
Department of Dermatology, Venereology, and Leprosy, R G Kar Medical College, Kolkata - 700 004, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2319-7250.139504

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The hereditary sensory and autonomic neuropathies (HSAN) are a group of very rare genetic disorders, characterized by prominent sensory as well as autonomic neuropathy without any motor involvement. Five main groups (type-I through type-V) of HSAN do exist. We report here a case of a chronic nonhealing leg ulcer in a young boy associated with anhidrosis, diagnosed as HSAN type-IV with osteomyelitis, for its rarity, and to emphasize the importance of considering this entity in the differential diagnoses of chronic nonhealing ulcers in the pediatric population.

Keywords: Anhidrosis, hereditary sensory and autonomic neuropathy type-IV, nonhealing ulcer, osteomyelitis

How to cite this article:
Dutta A, Ghosh SK, Chowdhury A, Ghosh A. Anhidrosis and nonhealing painless leg ulcer with osteomyelitis in a young boy. Indian J Paediatr Dermatol 2014;15:79-82

How to cite this URL:
Dutta A, Ghosh SK, Chowdhury A, Ghosh A. Anhidrosis and nonhealing painless leg ulcer with osteomyelitis in a young boy. Indian J Paediatr Dermatol [serial online] 2014 [cited 2021 Jun 23];15:79-82. Available from: https://www.ijpd.in/text.asp?2014/15/2/79/139504

  Introduction Top

The hereditary sensory and autonomic neuropathies (HSAN) are a group of rare autosomal recessive disorders, characterized by prominent sensory as well as autonomic neuropathy without any motor involvement. [1] HSAN are classified into five main groups (type-I through type-V) based on the inheritance patterns and clinical features. [2] HSAN type-IV is an exceedingly rare condition characterized by total insensitivity to pain and temperature associated with anhidrosis. Patients are liable to self-mutilate and may suffer from recurrent bouts of hyperpyrexia. Only a few reports of HSAN have been published in the dermatology literature. We report here a case of a chronic nonhealing leg ulcer in a young boy, diagnosed as HSAN type-IV with secondary osteomyelitis, for its rarity and interesting clinical presentation.

  Case report Top

A 4-year-old boy, born out of consanguineous parentage (first cousins), presented with multiple, painless, nonhealing ulcers on both the heels for the preceding 2 years. In addition, he had a history of recurrent bouts of high fever mainly during the summer season, which showed poor response to antipyretics. Since birth, he did not sweat even in the hot and humid weather. The boy had a history of repeated biting of his own lips, fingers, and toes, which led to self-mutilation. His birth and postnatal history was normal. His language and social development was delayed, but motor development was normal. He had normal bowel and bladder functions. There was no history of convulsion, abnormal movement, or history of similar illness in the first-degree relatives.

On examination, the boy was restless. We noticed a well-defined, nontender, deep-seated discharging ulcer (4 × 3 cm) with a necrotic base on his left heel. However, no evidence of discharge of any grain was found. The left ankle was hugely swollen [Figure 1]. A small shallow ulcer was also present on his right sole [Figure 2]a and b]. No regional lymphadenopathy was detected. The distal portions of a few fingers and toes showed signs of resorption. The range of motion was decreased in both the ankles. Although most of his teeth erupted normally, they were broken and lost [Figure 2c] due to repeated self-inflicted trauma. A few of finger and toe nails were dystrophic. However, his hair was normal. A few superficial ulcerations were evident on the tip of the tongue. The child was severely mentally retarded (full scale intelligent quotient = 30). Pain and temperature sensations were absent in all the limbs. There was no nerve thickening or motor deficit and vibration sense was normal. No other neurological abnormality was detected and the rest of the systemic examination was noncontributory. A starch-iodine test, done after sweating provocation, was negative. Pus culture from the leg ulcers grew out Staphylococcus aureus. Fungal and tubercular cultures were negative. Routine laboratory investigations including complete hemogram, renal profile, and serum uric acid level were normal apart from raised erythrocyte sedimentation rate and C reactive protein. Screening for HIV infection was negative. Nerve conduction velocity (NCV) studies and electromyography were normal. Skin biopsy showed normal histology with retention of eccrine glands. The boy was treated with systemic antibiotic. X-ray of the feet, done after 10 days of systemic antibiotic therapy, showed chronic osteomyelitic changes in the form of punched out erosion and osteolysis (in the posterio-inferior part) and ill-defined sclerosis (in the other parts) of right calcaneum [Figure 3].
Figure 1: Hugely swollen left ankle with discharging ulcer (picture at the time of presentation)

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Figure 2a and b: Healed ulcer on the right sole and resolving ulcer on the left heel (photograph taken 2-week after admission) (c) broken and absent teeth

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Figure 3a and b: Skiagram showing features of chronic osteomyelitis of the right calcaneum

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There was evidence of ulceration and presence of air in the adjacent soft tissue of the right heel. The radiographic features of the left foot were essentially normal.

Based on the clinical, laboratory, and radiological findings, a diagnosis of HSAN type-IV with secondary osteomyelitis of right calcaneum was made. The ulcers showed signs of healing with conservative management and the child was referred to orthopedics department for the management of bony changes.

  Discussion Top

Hereditary sensory and autonomic neuropathy type-IV is associated with several defects of the gene NTRK1 coding for the neurotrophic tyrosine kinase, a nerve growth factor receptor on chromosome 1q21q22. [3] These patients universally have congenital insensitivity to pain, recurrent febrile episodes, anhidrosis, self-mutilation, and mental retardation. [1] Multiple fractures, corneal ulceration, and aggressive behavior may also rarely be associated with this disorder. In addition to the absence of an axon flare following intra-dermal histamine, which is common to all types of HSAN, clinical diagnosis mainly depends on the fact that HSAN type-IV is the only HSAN that is associated with generalized anhidrosis. [4] There is no sweating with intradermal pilocarpine. [5] A NCV is usually normal. [2] Ultrastructural study of peripheral nerves reveals an almost complete lack of unmyelinated fibers and decreased number of small myelinated fibers. No evidence of demyelination or axonal regeneration has been noticed. [1] In the present case, the parents of the child did not give consent to undergo nerve biopsy and genetic study could not be done due to local unavailability.

Moreover, nerve biopsy studies may not be of practical benefit to the patient and it would not change the diagnosis or management of the condition. [6] Diagnosis of HSAN type-IV requires three clinical criteria, namely, anhidrosis, decreased pain perception, and mental retardation. [4] All of these features were evident in the present patient. The other features of HSAN type-IV in the form of signs of self-mutilation, presence of recurrent hyperthermic episodes (since infancy) in the presence of normal skin histology and NCV ruled out other possibilities including anhidrotic ectodermal dysplasia and also helped to reach the diagnosis in the present case.

Other variants of HSAN such as congenital sensory neuropathy (HSAN type-II), familial dysautonomia (HSAN type-III), and congenital insensitivity to pain (HSAN type-V) may mimic HSAN type-IV. [4],[7] Anhidrosis is the most important distinctive feature of HSAN type-IV, that is not present in other types of HSAN. Moreover, insensitivity to pain is not prominent in HSAN type-III. HSAN type-I is an autosomal dominant disorder that almost always affect the adults. Unlike HSAN type-IV, depressed deep tendon reflexes are a prominent feature of HSAN type-II and type-III. Self-mutilation is absent and there is only mild decrease in pain and temperature sensation in type-III HSAN. Mental retardation, which is common in HSAN type-IV is not a feature of HSAN type-V.

Self-mutilation and mental retardation may also be seen in cases of Lesch-Nyhan syndrome, where patients may present with growth retardation, hypotonia and delayed motor development. Sensory function remains intact, but motor function may be severely compromised.

They show different extra pyramidal features, such as, dystonia and choreoathetosis. In patients with Lesch-Nyhan disease, uric acid levels in the blood and urine are characteristically raised unlike in our patient. [8]

Anhidrotic ectodermal dysplasia is another important condition that presents with recurrent episodes of fever and anhidrosis. However, nervous system remains normal with intact pain and temperature sensation and histopathology shows absence of eccrine sweat glands in this condition. Other differentials of the present case were long standing poorly controlled juvenile diabetes mellitus, mycetoma, and leprosy.

However, detailed clinical examination and laboratory investigations could rule out these possibilities in the present case.

Hereditary sensory and autonomic neuropathy type-IV has been reported to be associated with Charcot arthropathy or joint subluxation and dislocation. Late secondary changes at the articular surface and osteonecrosis may also occur. Destructive changes of the calcaneum or other tarsal bones also have been rarely described in the literature. [6],[9] In this case, the radiological findings were more obvious in the right limb in spite of the fact that the left limb showed much more clinical signs of acute inflammation. This chronic osteomyelitic change of the right calcaneum was probably due to chronic or recurrent infections of the self-inflicted wounds or the trophic ulcers.

Hereditary sensory and autonomic neuropathy type-IV, rarely seen, is one of the most debilitating neuropathies of childhood with a high morbidity and a shortened life span. Apart from prevention and treatment of mutilating skin and bone lesions, no definitive therapy of HSAN type-IV is available.

Hence, early diagnosis is of paramount importance to prevent trauma to the anesthetized parts and appropriate management of the sequels of autonomic neuropathy. Furthermore, malignant hyperthermia and sepsis are major causes of mortality in the affected child with HSAN type-IV. Hence, every patient or their family members should be counseled about these potentially fatal complications. We further seek to emphasize the importance of considering this entity in the differential diagnoses of chronic nonhealing ulcers particularly when they are associated with anhidrosis and insensitivity to pain.

  References Top

1.Haworth AE, Thomas NH, Cook LJ, Ellison DW, Walker J. Hereditary sensory and autonomic neuropathy with anhidrosis (type IV). J R Soc Med 1998;91:84-6.  Back to cited text no. 1
2.Verhoeven K, Timmerman V, Mauko B, Pieber TR, De Jonghe P, Auer-Grumbach M. Recent advances in hereditary sensory and autonomic neuropathies. Curr Opin Neurol 2006;19:474-80.  Back to cited text no. 2
3.Tüysüz B, Bayrakli F, DiLuna ML, Bilguvar K, Bayri Y, Yalcinkaya C, et al. Novel NTRK1 mutations cause hereditary sensory and autonomic neuropathy type IV: Demonstration of a founder mutation in the Turkish population. Neurogenetics 2008;9:119-25.  Back to cited text no. 3
4.Axelrod FB, Gold-von Simson G. Hereditary sensory and autonomic neuropathies: Types II, III, and IV. Orphanet J Rare Dis 2007;2:39.  Back to cited text no. 4
5.Dua T, Sharma J, Singhal T, Arya VB. Hereditary sensory autonomic neuropathy Type IV. Indian Pediatr 2005;42:281-4.  Back to cited text no. 5
6.Marik I, Kuklik M, Kuklikova D, Kozlowsk K. Hereditary sensory and autonomic neuropathy type IV orthopaedic complications. J Pediatr Orthop B 2009;18:138-40.  Back to cited text no. 6
7.Karande S, Satam N. Hereditary sensory and autonomic neuropathy type IV. Indian Pediatr 2005;42:608-9.  Back to cited text no. 7
8.Jinnah HA, Baumann RJ. Lesch-Nyhan disease. e-medicine-Medscape. Available from: http//www.emedicine.medscape.com/article/1181356. [Last accessed on 2012 Aug 01].  Back to cited text no. 8
9.Rapp M, Spiegler J, Härtel C, Gillessen-Kaesbach G, Kaiser MM. Severe complications in wound healing and fracture treatment in two brothers with congenital insensitivity to pain with anhidrosis. J Pediatr Orthop B 2013;22:76-80.  Back to cited text no. 9


  [Figure 1], [Figure 2], [Figure 3]

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