Peri‐operative management of a patient with an ectodermal dysplasia (Rapp–Hodgkin) syndrome

Summary

We present the case of a 41‐year‐old man with Rapp–Hodgkin syndrome who underwent nasal septum deviation surgery under general anaesthesia. This syndrome is rare, with approximately 70 cases reported worldwide. It is one of a group of ectodermal dysplasia syndromes and results from the aberrant development of ectoderm during fetal development. Some of the clinical features may affect anaesthetic management. The most important considerations are potentially difficult airway management, the need for meticulous temperature control, and the importance of skin protection. This case was uneventful, but as there are few case reports on the management of patients with ectodermal dysplasia syndromes undergoing anaesthesia this report contributes useful knowledge. The pathogenesis and clinical features of Rapp–Hodgkin syndrome and the anaesthetic management for this patient are described.

Introduction

During embryonic development, the three primary germ layers evolve into the ectoderm, mesoderm and endoderm. The ectoderm differentiates into surface ectoderm and neuroectoderm. Surface ectoderm becomes the epithelial tissues of the skin, eyes, ears and the mucosal surface of the mouth, anus and nostrils. Hair, nails, tooth enamel, salivary glands, mucous glands and sweat also develop from surface ectoderm. Neural tissue develops from the neuroectoderm [1]. Ectodermal dysplasias are a group of around 150 disorders characterised by developmental defects in the structures derived from the embryonic ectoderm [2]. Rapp–Hodgkin syndrome (RHS) is one form of ectodermal dysplasia. Some consider RHS and Hay–Wells syndrome, also known as ankyloblepharon–ectodermal dysplasia–cleft lip/palate (AEC) syndrome, the same disease due to overlapping clinical features and the involvement of the same gene, TP63 [3]. This gene regulates epidermal proliferation and differentiation. Only 72 cases of RHS have been reported [4]. The clinical manifestations are heterogeneous and include cleft lip and/or palate, sparse hair, scalp or skin erosions, nail abnormalities, syndactyly, hypoplasia of the mid‐face, small mouth, micrognathia, dental abnormalities, vocal cord anomalies, lacrimal duct obstruction, anomalies of the eustachian tube, recurrent otitis media, hearing loss, abnormal respiratory mucous glands, depression of the immune system, recurrent respiratory infections, genitourinary abnormalities, inability to sweat and heat intolerance [3].

There is no cure for RHS, and treatment is symptomatic. However, innovative CRISPR/Cas9 gene editing technology may enable genetic repair in the future [5]. Patients with RHS may present for incidental surgery but frequently require dental, maxillofacial, orthopaedic and ear–nose–throat surgery. To our knowledge, there are no previous case reports on the anaesthesia care of patients diagnosed with RHS.

Report

A 41‐year‐old male with RHS (height 1.80 m, weight 81 kg) presented for surgical correction of nasal septum deviation. The patient had a history of hypohidrosis, frequent hyperthermia associated with exercise, micrognathia, alopecia, ungual dystrophy and oligodontia. He had a normal temperature on admission. He was not on any medication and had no other significant past medical history. Laboratory tests including full blood count, electrolytes and liver, renal and thyroid function were normal. Chest radiography was normal. He had never undergone a surgical procedure under general anaesthesia, although he had a past surgical history of minor dental repair under local anaesthesia. He had no family history of RHS. His diagnosis was made at the age of 19 years during investigation of xerosis, alopecia and exercise‐related heat intolerance.

The patient was positioned carefully and covered with a whole‐body forced air warming blanket (switched off). His core temperature prior to induction of anaesthesia was 36.5°C. General anaesthesia was induced with 2 mg.kg⁻¹ propofol, 3 μg.kg⁻¹ fentanyl and 0.6 mg.kg⁻¹ rocuronium. A 7.5‐mm internal diameter Ring–Adair–Elwyn (RAE) tracheal tube was inserted under direct laryngoscopy with a laryngoscope with a Macintosh blade without difficulty, after a Cormack‐Lehane 2A view was obtained. An oesophageal temperature probe was inserted, and a gauze throat pack placed in the oropharyngeal cavity. Anaesthesia was maintained with sevoflurane titrated to a Bispectral Index^® of between 40 and 60. The surgery took approximately 50 min. Oesophageal temperature was continuously monitored and maintained between 36–37°C, without the need for active warming or cooling. Before emergence and tracheal extubation, the patient received 1 g paracetamol, 30 mg ketorolac, 100 mg tramadol, 4 mg dexamethasone, 4 mg ondansetron and 150 mg sugammadex. In the post anaesthetic care unit, axillary temperature was monitored every 15 min for 1 h. Postoperative recovery was uneventful, and he was transferred to the ward, where the temperature was regularly monitored every 4 h. The patient was discharged home the following day (Fig. 1).

Figure 1.

Photograph of the patient, demonstrating micrognathia.

Discussion

Currently, there are about 150 different known types of ectodermal dysplasias. In an attempt to classify these, different subgroups are described according to the presence or absence of four primary ectodermal dysplasia (ED) defects: ED1 – trichodysplasia (hair dysplasia); ED2 – dental dysplasia; ED3 – onychodysplasia (nail dysplasia); and ED4 – dyshidrosis (sweat gland dysplasia) [6].

The three most recognised ectodermal dysplasia syndromes are ectrodactyly‐ED‐clefting syndrome, RHS and ankyloblepharon–ectodermal dysplasia–cleft lip/palate (AEC) syndrome or Hay–Wells syndrome [6]. It has been suggested that the distinction between RHS and Hay–Wells syndrome should be abandoned in favour of the broader AEC syndrome [3].

To date, there are no known case reports of RHS‐related anaesthesia procedures, and the anaesthetic recommendations derive from published reports about management of other ectodermal dysplasias.

The main issues related to patients with RHS undergoing surgery are the potential for a difficult airway, perioperative temperature dysregulation and skin fragility. Our suggested considerations for the peri‐operative management of patients with RHS are summarised in Table 1.

Table 1.

Clinical features and perioperative considerations for patients with Rapp–Hodgkin syndrome.

RHS is one of a large group of rare ectodermal dysplasia syndromes RHS may be considered part of AEC syndrome Caused by mutation of the TP63 gene (as in Hay–Wells syndrome) Family history frequent, but de novo cases may occur Abnormalities occur in hair, teeth, nails, face, palate, lips, ears, genitals, immune system, and sebaceous and sweat glands Predisposes to skin erosions and infections, inability to sweat, heat intolerance, frequent hyperthermia, airway abnormalities (e.g. cleft palate), ear disturbances and respiratory infections Recommendations: anticipate airway difficulties; position carefully and protect skin; monitor and control core temperature Avoid anticholinergic drugs and nitrous oxide (to prevent post‐operative middle ear dysfunction). Anti‐pyretic drugs may be appropriate to avoid fever. Consider regional anaesthesia Ambulatory surgery may not be suitable

RHS, Rapp–Hodgkin syndrome; AEC, ankyloblepharon–ectodermal dysplasia–cleft lip/palate.

Cleft lip, cleft palate, maxillary hypoplasia, micrognathia, loose teeth and abnormal vocal cords (e.g. stenosis) may predispose patients to difficulties with facial‐mask ventilation, supraglottic airway device insertion, or tracheal intubation. The 2022 American Society of Anesthesiologists guidelines for the management of difficult airway recommend awake intubation if the patient has combined predicted difficult intubation and ventilation with facemask/supraglottic airway, increased risk of aspiration, intolerance of brief apnoea or expected difficult invasive airway [7].

In RHS, abnormal sweat glands and the inability to sweat predispose patients to temperature increases, and hyperthermia and fever may be challenging. Accordingly, anticholinergic drugs should be avoided, and the use of antipyretic drugs may be appropriate for avoiding fever. Hyperthermia is uncomfortable for conscious patients, increases the metabolic rate and increases cardiovascular demand. Causes of intra‐operative hyperthermia include excessive warming, sepsis, uncontrolled metabolism (e.g. thyroid storm, neuroleptic malignant syndrome and malignant hyperthermia), transfusion reactions and the presence of blood in the cerebral fourth ventricle [8]. Special attention should be paid to temperature monitoring during the care of patients with RHS. All patients should have their temperature recorded before induction, every 30 min during surgery and every 15 min in the recovery room until the normal temperature is achieved [9]. The methods available to estimate body temperature include measurements in the pulmonary artery, distal oesophagus, nasopharynx, tympanic membrane, bladder, rectum and skin. The use of oesophageal probes provides an accurate estimation of the core temperature when properly placed in the distal oesophagus (approximately 45 cm from the adult nose). However, mispositioning may yield false results and lead to harm. Nasopharyngeal temperature monitoring can be achieved by positioning an oesophageal probe above the palate. Tympanic monitoring requires a probe to be placed in contact with the eardrum. The axillary temperature may be a reasonable alternative in selected patients if positioned carefully near the axillary artery and the patient's arms are kept to the side [8]. The core temperature is the best indicator for effectively detecting hyperthermia, fever and hypothermia [8], and patients with RHS are best monitored through a combination of methods to avoid errors.

Patients with RHS may have a degree of immunosuppression and abnormalities of the respiratory mucous glands may exist. Skin erosion may occur easily and may be difficult to treat. Careful positioning should be followed to protect the skin. The risks and benefits of using depth of anaesthesia monitoring electrodes, which may cause skin abrasions, should be discussed with the patient. Strict attention to eye protection should be followed. Fragile mucosal surfaces may predispose patients to lacerations and haemorrhage. Airway manipulation should be performed gently, and lubricants should be used liberally. Because of possible ear and eustachian tube dysfunction, nitrous oxide should be avoided to prevent postoperative hearing impairment and pain. Genitourinary abnormalities may complicate bladder catheterisation. Ambulatory surgery may not be suitable for these patients.

In conclusion, patients with RHS require a careful approach to airway management, continuous temperature monitoring under anaesthesia and careful positioning.