Patient characteristics in tardive COVID-19 pseudoperniosis: a case series of 16 patients.

BACKGROUND: Acute pseudoperniosis (PP) has a recognized association with COVID-19 and tends to occur without cold precipitation in young, healthy patients, often without a clear history of COVID-19. These lesions usually resolve within 2 weeks and without long-term sequelae. In the early months of 2021, patients with delayed and protracted PP began to emerge. We have called this presentation 'tardive COVID-19 PP (TCPP)'. AIM: To consolidate and expand knowledge on TCPP, we describe the clinical characteristics, treatments and outcomes of 16 patients with TCPP who were reviewed by our outpatient dermatology service. RESULTS: The initial clinical manifestations were erythema, swelling and PP of the fingers in 56.2%, and of the toes in 31.2%, desquamation in 56.2% and acrocyanosis in 12.5%. Ten patients had eventual involvement of all acral sites. The median duration of symptoms was 191 days. Six patients reported close contact with a confirmed or suspected case of COVID-19, but only two had positive COVID-19 tests. Four patients experienced complete or almost complete resolution of symptoms, while the rest remain under active treatment. CONCLUSION: Unlike acute PP, TCPP has a protracted and delayed presentation that is typically associated with profound acrocyanosis. Patients with TCPP represent a new phenomenon that is part of the post-COVID-19 syndrome, with risk factors and pathophysiology that are not yet fully understood. Our data indicate that likely predisposing factors for developing TCPP include young age, a preceding history of cold intolerance and an arachnodactyloid phenotype. Anorexia, connective tissue disorders or sickle cell trait may also predispose to TCPP. In addition, low titre antinuclear antibody positivity, the presence of cryoglobulins, or low complement levels may represent further risk factors. Finally, prolonged low temperatures are also likely to be contributing to the symptoms.

Endoscopic observations on laryngeal symmetry and movements in young racing horses.

An endoscopic survey of young race horses was performed to examine the prevalence and character of laryngeal movements during quiet respiration. The main aim was to determine whether those arytenoid movements which could possibly reflect the efficiency of left dorsal cricoarytenoid muscle function changed over a period of time. Of the 452 horses examined, 439 were Thoroughbreds and 23 were Standardbreds, 250 were less than 2 years of age (6-21 months), and 202 were 2 years old. One hundred and nine of these horses were examined again 16 months later. Arytenoid movements were given one of four grades. Grades 1 and 2 were considered normal and unlikely to be the result of abnormal left dorsal cricoarytenoid muscle function, whilst grades 3 and 4 were considered likely, or almost certainly, the result of abnormal left dorsal cricoarytenoid muscle function. The percutaneous prominence of the muscular process of left and right arytenoid cartilages, endoscopic arytenoid movement on left and right sides, age, sex and breed was recorded. Chi squared analysis was used to determine the association between age, breed, sex and the other recorded variables, and the presence or absence of abnormal laryngeal movements. At the first examination, 48% of the horses had grade 1, 37% grade 2, 15% grade 3 and 0.2% grade 4 left laryngeal movements. Of the horses examined I6 months later, 52% had grade 1, 33% grade 2, 14% grade 3 and 1% grade 4 left laryngeal movements. Fifteen percent of horses with grade 1 and 9% with grade 2 initially were found to be grade 3 at the subsequent examination. Conversely, 53% of horses with grade 3 initially were found to be grade 1 and 21% grade 2 at the subsequent examination. One horse that was grade 3 at the initial examination was grade 4 at the subsequent examination. Overall, 43% of horses were graded the same, 29% were given a better grade and 28% were given a worse grade. Age and sex were not associated with abnormal left laryngeal movements. The presence of abnormal arytenoid movements was significantly less in Standardbreds, but significantly higher in those horses that had a more prominent muscular process of the left arytenoid cartilage. The number of grade 2 and 3 laryngeal movements recorded on the left side was significantly higher than the right. It was concluded that asymmetrical laryngeal movements are common in young race horses; at this age laryngeal movements may interchange between what is considered normal and abnormal; the proportion of young horses with normal or minor variations in their left arytenoid movements that develop more obvious degrees of asynchrony is low (12%); and the proportion of horses considered to have endoscopic evidence of deficient left abductor muscle function that eventually develop laryngeal hemiplegia is also low (5%).

Neurogenic laryngeal paralysis in the dog.

Idiopathic laryngeal paralysis in dogs is now a frequently recognised disorder, particularly in certain breeds such as the Labrador retriever, Afghan hound and Irish setter. Since it occurs in the older animal, distinguishing the clinical signs and their significance from lower respiratory tract or cardiac disease can be challenging. At present little is known about its aetiology and therefore the treatment is directed at relieving the clinical signs. Recent work indicates that arytenoid cartilage lateralisation achieves the best results as a method of surgically correcting the laryngeal obstruction. However, it should be remembered that the potential benefits of surgery should be assessed for each individual, taking into account the presence of concurrent disease and lifestyle of the dog.

An experimental evaluation of castellated laryngofissure and bilateral arytenoid lateralisation for the relief of laryngeal paralysis in dogs.

The aim of this study was to compare the efficacy of 2 surgical procedures for providing an adequate laryngeal airway in dogs after surgically induced laryngeal paralysis. The laryngeal function of 10 healthy, adult experimental dogs was assessed by clinical examination, laryngoscopy, arterial blood gas measurement and analysis of tidal breathing flow-volume loops before, and after, bilateral recurrent laryngeal neurectomy. A castellated laryngofissure with vocal fold resection was done on 5 dogs and bilateral arytenoid cartilage lateralisation performed on the remaining 5 dogs. Six weeks later, the laryngeal function of the 10 dogs was reassessed, before the dogs were killed and a necropsy performed. The visible changes in laryngeal structure were recorded. Both surgical procedures alleviated some of the airway obstruction caused by the bilateral recurrent laryngeal neurectomy, but bilateral arytenoid cartilage lateralisation produced more consistent clinical improvement, a wider rima glottidis, increased inspiratory air flow and a significant increase in post-operative arterial oxygen tension.

Iohexol myelography in the horse.

Iohexol, a water soluble non-ionic contrast agent, was evaluated for myelography in the horse. Both 300 and 350 mg iodine/ml iohexol gave diagnostic cervical myelograms. Pathological changes were limited to extradural oedema and an increase in the number of white blood cells and specific gravity in the cerebrospinal fluid two days after myelography. This increase in white blood cells in the cerebrospinal fluid was, however, much less than that recorded by other authors using metrizamide and iopamidol contrast media. These findings indicate that iohexol is a less irritant myelographic contrast agent than those previously evaluated in the horse.

Further evidence for a central nervous system component in equine laryngeal hemiplegia.

Evidence for a central nervous system component of the distal axonopathy associated with equine laryngeal hemiplegia was found in this survey of 33 horses (control, 15; subclinical, 8; clinical, 10). Significantly higher numbers of axonal spheroids were present in sections of the lateral cuneate nuclei in layngeal hemiplegic horses than in those unaffected by the disease.

Surgical relief of severe laryngeal malformation in an English Bulldog.

A 22 month old English Bulldog was presented with progressive upper airway obstruction associated with an elongated soft palate, tonsillitis, everted laryngeal saccules and laryngeal malformation. Surgical management of the case consisted of resection of the elongated soft palate and everted laryngeal saccules, unilateral tonsillectomy and correction of the laryngeal stenosis. The latter was achieved by using a castellated incision through the laryngeal cartilages and first tracheal ring. From this case, it is postulated that, at least in some cases, the common upper airway obstruction syndrome in Bulldogs may not be due to laryngeal collapse as previously thought but rather to congenital malformation of the laryngeal cartilages.

The pathogenesis of equine laryngeal hemiplegia--a review.

Recent research on the muscular and nervous changes which occur in idiopathic equine laryngeal hemiplegia has indicated that many of the traditional concepts of the aetiology of this disease are erroneous. In light of the new knowledge gained, the various predispositions and possible causes of laryngeal hemiplegia are discussed, and it is suggested that the underlying mechanism of axonal damage in this neuropathy of horses may be related to abnormal energy metabolism in the axon.

Equine laryngeal hemiplegia. Part III. A teased fibre study of peripheral nerves.

Individual nerve fibres were isolated from the recurrent laryngeal and some distal hindlimb nerves, in an investigation of equine laryngeal hemiplegia. One hundred teased fibres were obtained from each of three sampling sites on both left and right recurrent laryngeal nerves, from 15 Thoroughbred horses. These fibres were graded descriptively and internode lengths measured. A distal distribution of pathology was demonstrated in all groups studied, but was most severe in the clinical group of horses. The predominant change was one of short thinly myelinated internodes interspersed amongst normally myelinated internodes, indicating remyelination of previously demyelinated areas of nerve fibre. Such pathological change was also reflected by the decreased mean internode length, and its increased variability associated with disease. However, it was determined statistically that these abnormal internodes were grouped along particular nerve fibres, rather than being randomly distributed between all nerve fibres. This is thought to indicate myelin sheath changes secondary to underlying axonal pathology. Thus it was concluded that the primary pathology was likely to be axonal in nature, while the high incidence of demyelination changes was a reflection of the chronic nature of the disease process. Thus, the distal distribution of pathology, the primary axonal involvement, the presence of changes in left and right recurrent laryngeal and distal limb nerves, all support the classification of equine laryngeal hemiplegia as a distal axonopathy.

Equine laryngeal hemiplegia. Part IV. Muscle pathology.

This study confirmed that neurogenic muscle pathology exists in intrinsic laryngeal muscles supplied by the recurrent laryngeal nerves in horses subclinically and clinically affected with laryngeal hemiplegia. An important additional observation was the occurrence in three out of four laryngeal hemiplegic horses of neurogenic muscle changes in a hindlimb muscle, the extensor digitorum longus, a muscle supplied by another long peripheral nerve. This finding suggests that a polynenropathy exists in laryngeal hemiplegic horses, and supports the classification of this disease as a distal axonopathy. Comparison of the degree of pathology in the intrinsic laryngeal muscles and that of the recurrent laryngeal nerves innervating them, demonstrated a strong correlation between the extent of damage in the distal left recurrent laryngeal nerve and the overall degree of muscle pathology. The muscle damage in clinically affected horses is a reflection of the nerve damage present in the most distal portion of the recurrent laryngeal nerve. The more variable pathological changes found in proximal levels of the left and right recurrent laryngeal nerves probably reflects the ongoing nature of the pathological process affecting nerve fibres. The existence of a subclinically affected group of horses, the earliest involvement of an adductor, the left cricoarytenoideus lateralis muscle, and the presence of changes in the right intrinsic laryngeal muscles all confirmed the findings of previous workers.

Equine laryngeal hemiplegia. Part V. Central nervous system pathology.

Evidence of long central nerve fibre degeneration (axonal spheroids) in the lateral cuneate nuclei was found in all eight Thoroughbreds affected clinically and subclinically with equine laryngeal hemiplegia, but in only one of six control animals. It was considered that these spheroids may signify a central nervous component of the disease process of laryngeal hemiplegia although until further investigations are performed no firm conclusions regarding the relationship of these findings with laryngeal hemiplegia could be made. Examination of the left and right nucleus ambiguus of clinical and subclinical laryngeal hemiplegic horses revealed no pathological alterations.

Equine laryngeal hemiplegia. Part I. A light microscopic study of peripheral nerves.

This light microscopic investigation of 15 Thoroughbred horses provided substantial evidence for the classification of equine laryngeal hemiplegia as a distal axonopathy. Morphologic and morphometric examinations were performed on resin embedded recurrent laryngeal nerves from control, subclinical and clinical laryngeal hemiplegic animals. In the latter group of animals some distal hindlimb nerves were also examined. A distally graded loss of myelinated fibres selectively affecting those of large diameter was demonstrated in both left and right recurrent laryngeal nerves. Morphologic evidence of similar pathological changes in long hindlimb nerves was also present. An explanation for the early involvement of the cricoarytenoideus lateralis muscle in the course of laryngeal hemiplegia, was offered by the demonstration of more large diameter fibres in the branch of the recurrent laryngeal nerve innervating it, thus making it more susceptible to the disease process.

Equine laryngeal hemiplegia. Part II. An electron microscopic study of peripheral nerves.

The recurrent laryngeal nerves were examined by electron microscopy in five control, four subclinical and four clinical laryngeal hemiplegic horses. In addition, the peroneal nerve was examined in two horses in the latter group. The distally distributed loss of large myelinated fibres in the left recurrent laryngeal nerve seen by light microscopy was confirmed. In addition, active axonal pathology was found to be more evident than indicated by light microscopic investigations. The onion bulb formations observed indicated the repetitive nature of the damaging influence to nerve fibres. Although the pathological changes were most obvious in the distal left recurrent laryngeal nerve, alterations similar in type and distribution were present in other areas of the left and right nerves, and in the distal hindlimb nerves. The observation of fibres with inappropriately thick myelin sheaths relative to their axonal calibre, was confirmed statistically by determining the regressions of axis cylinder perimeter against the number of myelin lamellae. In conclusion, the peripheral nerve pathology of equine laryngeal hemiplegia was demonstrated to be a distally distributed loss of myelinated fibres, with considerable active axonal damage, in conjunction with axonal atrophy. These features suggest that this disease may be classified as a distal axonopathy.

Stringhalt in horses: a distal axonopathy.

A detailed investigation of the neuropathology of a horse affected with stringhalt was performed. Qualitative and quantitative light and electron microscopy, and single teased fibre preparations of peripheral nerve demonstrated predominantly axonal degeneration, the stage of which was appropriate for the duration of clinical signs. There was selective involvement of large myelinated nerve fibres. A proximal to distal increase in the severity of pathological changes was present in the peripheral nerves. The long left recurrent laryngeal nerve was the most severely affected, followed in order by its right counterpart, the hindlimb and forelimb nerves. Neurogenic atrophy of muscles innervated by affected peripheral nerves also showed a distally graded increase in severity. No lesions were observed in the central nervous system. It was concluded that this disease should be classified as a distal axonopathy.

Right-sided laryngeal dysfunction in a horse.

A two year old Thoroughbred colt was presented after a clinical diagnosis of right sided laryngeal hemiplegia had been made. On endoscopic examination the right arytenoid cartilage was immobile during respiration while the left moved normally. Post-mortem examination revealed an abnormal shape of the cricoid and thyroid cartilages which resulted in absence of the right cricothyroid articulation. The defect was thought to be congenital in origin.

A review and some observations on stringhalt.

A review of the literature on stringhalt in horses is presented, including the aetiology, clinical signs, pathology and treatment of this disease. Three New Zealand outbreaks of stringhalt are reported and discussed. The occurrence of these (and most previously reported outbreaks) in the late summer and autumn, and the association of the disease with various weeds, indicates a likely toxic aetiology.

Roaring in Clydesdales.

An endoscopic survey was performed to assess arytenoid cartilage movement during quiet respiration in 48 Clydesdale horses. Physical characteristics which could influence the length of the recurrent laryngeal nerves were also recorded from these horses and the relationship of these characteristics to the presence of abnormal left arytenoid cartilage movements was assessed statistically. Some degree of abnormal arytenoid movement was observed in 50% of the animals over one year of age. No significant correlation between sex, age, estimated weight, height, or neck length could be found although affected animals were, on average, slightly taller, lighter and longer necked.