Hoffmann Disease Research Articles

Exploring the Efficacy and Safety of Interleukin‐23 Inhibitors in Dissecting Cellulitis of the Scalp: A Comprehensive Review

ABSTRACTBackgroundDissecting cellulitis of the scalp (DCS), also known as perifolliculitis capitis abscedens et suffodiens or Hoffmann disease, is a rare chronic inflammatory scalp condition with an unknown etiology. The US Food and Drug Administration (FDA) has recently approved multiple interleukin‐23 (IL‐23) inhibitors for chronic‐plaque psoriasis, and their off‐label use has shown promise in treating various dermatological conditions, including DCS. This review assesses the efficacy and safety of IL‐23 inhibitors for DCS, aiming to support potential FDA approval for severe refractory cases.MethodsA comprehensive literature search was conducted in February 2024 using MEDLINE, PUBMED, and Google Scholar with the keywords “Dissecting cellulitis,” “DCS,” “Interleukin‐23 inhibitors,” “IL‐23,” and “Biologics.” The search focused on identifying studies reporting the use of IL‐23 inhibitors in DCS treatment.ResultsThe search identified five cases where IL‐23 inhibitors were used to treat DCS. All patients were male, aged 17–65 years, with multiple comorbidities in four cases, primarily hidradenitis suppurativa and acne conglobata. The IL‐23 inhibitors Risankizumab, Guselkumab, and Tildrakizumab were used, resulting in significant clinical improvement, near‐complete remission, and hair regrowth. Additionally, psychosocial improvements were noted in two cases, with no reported adverse effects.ConclusionIL‐23 inhibitors have shown remarkable efficacy in treating severe DCS, with significant clinical and psychosocial improvements and a favorable safety profile. These findings support the consideration of FDA approval for IL‐23 inhibitors as a treatment option for refractory DCS cases, offering hope for patients with this challenging condition.

Aseptic Alopecic Nodule of the Scalp (NAAS) Simulating Hoffmann's Disease (HD), Efficacy of Intra-Lesional Corticotherapy: 03 Observations at the Bamako Dermatology Hospital (HDB)

The alopecic aseptic nodule of the scalp (NAAS) is a recently described entity known as a "pseudocyst of the scalp". It can be confused with dissecting folliculitis of the scalp (Hoffmann's disease) by certain clinical signs. We report three cases of NAAS mimicking MH with favourable evolution under doxycycline associated with intra-lesional corticotherapy. Case 1: A 36-year-old man presented with painful nodules of the scalp. Examination revealed two fluctuating subcutaneous nodules measuring 4 and 5 cm, both painful. The skin opposite the nodules was alopecic and not scarred. Case 2: A 28-year-old man presented with a scalp nodule that had been present for 3 months. Clinical examination revealed a fluctuating, painful subcutaneous nodule measuring 7cm, alopecic and non-scarring, with surrounding small patches of alopecia. In addition, inflammatory acne lesions were noted on the face. Case 3: A 33-year-old obese male smoker presented with a scalp nodule. Examination revealed a painful subcutaneous nodule measuring 3 cm, with smooth alopecic skin. Discussion: The pathophysiology of NAAS remains poorly understood, and a link with the spectrum of follicular occlusion pathologies has been suggested. Inflammatory acne was observed in two of our patients. The biopsy was non-specific; the pus came back sterile in all cases; after aspiration, the patients benefited from intra-lesional corticosteroid therapy associated with doxycycline 100mg/dr with a good evolution. Conclusion: Aseptic alopecic nodules of the scalp are clinically similar to folliculitis dissecans of the scalp. Certain clinical signs can help the practitioner to make the correct diagnosis in order to avoid aggressive treatment.

A rare case of type1 proximal spinal muscular atrophy (werdnig - hoffmann disease) – a case report and review of literature

Spinal Muscular Atrophy (SMA) is an autosomal recessive Motor Neuron Disease (MND) with mutation of Survival motor neuron 1 (SMN1) gene located in chromosome 5(5q13.2) characterized by diffuse proximal and distal muscle weakness. Here the authors report a case of SMA in a 3 months old male infant with hypotonia of proximal muscles in both upper limbs and lower limbs with characteristic fasciculations of tongue and confirmed by genetic studies.

Dissecting cellulitis of the scalp treated by tumour necrosis factor inhibitors: a case series.

Dissecting cellulitis of the scalp (DCS), also known as Hoffmann disease or perifolliculitis capitis abscedens et suffodiens, is a rare disease characterized by chronic inflammation of the scalp. Treatment is difficult and often disappointing. To report our experience of TNF inhibitors in a series of patients with DCS. We conducted a monocentric retrospective study of nine patients with DCS treated with TNF blocker after failure of other conventional treatments. After a mean duration of treatment by TNF inhibitors of 17 ± 16 months, four patients (44% versus 0%) had a Physician's Global Assessment score of 0 or 1. We observed a 67% reduction in the number of inflammatory nodules, an 88% reduction in purulent drainage and a 45% improvement in Dermatology Life Quality Index. The mean treatment satisfaction index was 6.6 ± 1.6 out of 10. Our study suggests that TNF inhibitors are effective against disease activity and may improve quality of life in the management of DCS refractory to conventional treatments.

Nutritional Support for Child with Werdnig–Hoffmann Spinal Muscular Atrophy

Some of the severe manifestations of Werdnig-Hoffmann disease are the pseudobulbar and bulbar syndromes complicated by the hypotrophy of the various degrees of severity. The clinical case of the nutritional support for the child with grade II hypotrophy that complicated the course of Werdnig–Hoffmann disease in one-year-old child is presented. The purpose of this study is to assess the effect of Clinutren Junior high-calorie formula for children from 1 to 10 years of age on the growth and development of the child diagnosed with type I spinal muscular atrophy. The results were analyzed according to the degree of change in the following anthropometric data: mid-arm circumference, mid-hip circumference, the size of the skin fold in the periumbilical region, as well as laboratory data, as follows: albumin, total protein, lymphocytes.

Spinal muscular atrophy

Spinal muscular atrophy (SMA) is one of the leading causes of death in infants and young children from heritable diseases. Patients diagnosed with SMA develop symmetrical progressive muscle weakness and atrophy secondary to degeneration of alpha motor neurons. Approximately 95% of patients have a homozygous deletion of survival motor neuron 1 (SMN1) gene in exon 7 with an autosomal recessive mode of inheritance. Considering the high frequency of consanguineous marriage in Tunisia, autosomal recessive disorders, such as SMA, seems to be more prevalent in our population. Between 1992 and 2019, 70 patients were referred to our department for SMA. We performed a retrospective analysis of the data of these 70 cases. The diagnoses were confirmed by clinical symptoms, electroneuromyography (ENMG), and sometimes by muscle biopsy. For each patient, we determined clinical features such as the age of onset, muscle weakness and atrophy, motor function and the disease progression. Polymerase chain reaction (PCR) combined with restriction fragment length polymorphism (RFLP) was performed for 33 patients to detect the deletion of exon 7 and exon 8 of SMN1 gene, as well as multiplex PCR for exon 5 and 13 of NAIP gene. 70 cases of chronic proximal spinal muscular atrophy are reported. The age of onset of these disorders is variable, ranging from the neonatal period to adulthood. Clinically, SMA is categorized into four types: type I is the most severe and primarily affects newborns (4.3% in our study), types II and III are intermediate forms(72.85%), and type IV is the mildest form with adult-onset which represented 22.85% of cases. Neurological examination found a myopathic syndrome in all patients, osteotendinous areflexia in the majority of cases (55/70 - 78.6%). Fasciculations were found in 15 cases (21.5%). Inbreeding was noted in about two-thirds of families (55.71%). The presence of similar cases was found in 20% (14/70). Bulbar involvement was rarely observed (5/70 - 7.14%). ENMG showed a chronic neurogenic pattern. Genetic testing was performed in only 33 SMA patients, 15 had homozygous deletion of exons 7 and/or 8 of SMN1 gene (45.4%) and 3 for the NAIP gene. All patients presenting SMA type 1 died early. In the other types of SMA, a slowly and progressive worsening occurred during follow-up. Several forms of SMA have been described in association with different gene mutations and significant phenotypic variability. The most frequent form of SMA is the autosomal-recessive proximal SMA, or SMN1-linked SMA. Type1 SMA (Werdnig–Hoffmann disease) is the most common and severe form, representing about 45% of SMA case. As was shown in our cohort,the clinical features associated with this disorder are muscle weakness and atrophy with a predominantly proximal muscle distribution. Lower limbs are more involved than upper limbs. Bulbar and respiratory muscles involvement is seen in advanced stage of the disease particularly in type1 SMA. With the advent of molecular biology techniques, SMN gene deletion study represents nowadays a useful and reliable tool to confirm the diagnosis of SMA suspected clinically. Deletions of NAIP gene were mainly seen in severely affected patients, it is considered as poor prognosis marker. The elucidation of the genetic and molecular basis of SMA described above, suggested several possible therapeutic approaches based on the general principle of increasing the expression of the SMN protein. These strategies include pharmacologic or gene-based therapies to increase SMN2 expression (leading to more full-length SMN mRNA), antisense oligonucleotide-based therapies to favor incorporation of exon 7 into SMN2-derived mRNA transcripts, and viral mediated therapies to replace the entire SMN1 gene. In December 2016, a new agent, nusinersen (an antisense oligonucleotide), was approved by the FDA. Early diagnosis and initiation of this treatment are necessary to achieve optimal outcomes. Many other novel therapies for SMA are in the pipeline. Supportive care remains mandatory in the management of SMA to slow or prevent respiratory failure, nutritional compromise, scoliosis, and joint contractures… Spinal muscular atrophy is a motor neuron disease of infancy, childhood and adulthood and the genetics and pathophysiology has received extensive study over the last twenty years. These studies shed a new light on the pathogenesis of the disease and permit the determination of new therapeutic target. Many disease modifying therapies are developed (some of them are now approved) and completely transform the natural course of the disease.

Werdnig-Hoffmann Disease in A Female Child: A Rare Case Report

Spinal muscular atrophies (SMAs) are rare degenerative diseases that affect motor neuron. It is inherited as autosomal recessive disorder and mainly affect male baby but female may be affected. Disease can occurs all age groups but more severe form of the disease generally involved paediatric age group. Most severe infantile form also known as type 1 SMA or Werdnig- Hoffmann disease usually presented before the age of 6 months with generalisedhypotonia with recurrent respiratory tract infection. Definite diagnosis is by genetic study and treatment is generally supportive and prognosis is poor. Here we present such rare disease in a female child.

Insufflation–exsufflation devices in post-operative respiratory failure: Case report

IntroductionPatients suffering from a neuromuscular disease have a greater likelihood of postoperative respiratory failure. Sometimes, this complication does not respond to non-invasive mechanical ventilation. Case reportPerioperative management of a patient with Werdnig–Hoffmann disease who underwent bilateral coronoidectomy due to trismus. The postoperative period was hampered by the patient's poor respiratory mechanics, inducing the appearance of atelectasis. Despite the application of preventive non-invasive mechanical ventilation, the patient suffered respiratory failure and required endotracheal intubation. Finally, the respiratory weaning was achieved after the application of insufflation–exsufflation devices associated with non-invasive mechanical ventilation. ConclusionThe application of insufflations–exsufflation devices in the immediate post-operative period of patients with neuromuscular diseases promotes the proper respiratory evolution of a patient considered impossible to extubate.

1857 Peer Counseling of Adolescent Handicapped Children after sex Education: The Pilot Study

BackgroundMost pediatric nurses recognize that the child with special needs requires the proper sex education, but we have avoided it so far, possibly unconsciously or just to avoid any unpredictable...

Medical Considerations of Long-Term Survival of Werdnig–Hoffmann Disease

To report intercurrent nonrespiratory complications of unprecedented survival for Werdnig-Hoffman disease (spinal muscular atrophy type 1 [SMA 1]). A retrospective chart review and caregiver questionnaire for 103 consecutively referred SMA 1 patients for whom death was prevented during infancy. Overall, 15 of 63 (23.8%) respondents had severe, symptomatic bradycardias. Thirteen of 25 males had bilateral cryptorchidism, and two were unilateral. Ten of 42 (24%) respondents had recurrent oral candidiasis, and eight (19.0%) had recurrent nonoral candidiasis. All patients had hip dislocation/subluxation. They had collapsing spines and scoliosis by 1 yr of age. Ninety-six had indwelling gastrostomy/nasogastric tubes before 24 mos of age. Twenty-six underwent fundoplication to decrease reflux. Fifty-seven were on modified elemental diets with reported benefits. About one half had early pubarche. Three patients had episodes of acute pancreatitis. One untreated patient died of candidal endocarditis at 4 mos of age, and a second child had mitral valve candidiasis on autopsy. Prolonged survival of SMA 1 results in a high incidence of concomitant medical conditions that need to be addressed.

Werdnig–Hoffmann disease with congenital hypothyroidism

Congenital hypothyroidism is often associated with other congenital anomalies. In some instances it is difficult to differentiate congenital hypothyroidism from Werdnig-Hoffmann's disease. We report a case of congenital hypothyroidism associated with Werdnig-Hoffmann's disease that appears to be the first of its kind in the literature.

Oxidative stress and disturbed glutamate transport in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a hereditary motor neuron disease, and three clinical subtypes of autosomal recessive SMA, including Werdnig Hoffmann disease (type 1), have been shown to be induced by deletion within the same genes. In order to clarify the pathogenesis of motor neuron degeneration in SMA, we immunohistochemically examine the expressions of oxidative stress-related materials (oxidative products) and glutamate transporters, which can prevent glutamate neurotoxicity, in five autopsy cases of SMA type 1. Age-matched controls did not show any deposition of oxidative products in the brain. In contrast, the abnormal deposition of 4-hydroxy-2-nonenal-modified protein, a product of membrane lipid oxidation, was observed in the spinal motor neurons in three cases, although the motor neurons did not show an increase of nitrotyrosine, which was observed in adult-onset amyotrophic lateral sclerosis. In addition, the nuclei of neurons and glial cells in the precentral gyrus, thalamus or cerebellar cortex were immunoreactive for 8-hydroxy-2′-deoxyguanosine in two cases, which was one of the most commonly used markers for oxidative DNA damage. Regarding glial glutamate transporters, three of five cases of SMA type 1 showed a reduction in immunoreactivity for excitatory amino acid transporter-1 (GLAST) in the ventrolateral nucleus of the thalamus, in which there was neither neuronal loss nor gliosis in routine histochemistry. One case, having mechanical ventilation, demonstrated a reduced expression of another glial glutamate transporter (GLT-1) throughout the central nervous system. These data suggest that oxidative stress and disturbed glutamate transport can partly be involved in the motor neuron devastation and/or latent thalamic degeneration in SMA type 1.

Anterior horn cell disease and olivopontocerebellar hypoplasia

To date, fewer than 30 cases of anterior horn cell disease with associated olivopontocerebellar hypoplasia have been reported. We describe five patients and review the literature on this uncommon disorder. In addition to a syndrome of progressive spinal muscular atrophy similar to that seen in Werdnig–Hoffmann disease, this disorder is characterised by hypoplasia of the olivary nuclei, pons, and cerebellum. Additional clinical features may include dysmorphism, abnormal eye movements, stridor, congenital joint contractures, and enlarged kidneys. Pontocerebellar hypoplasia may be associated with posterior fossa cystic malformations, cerebral atrophy, and a demyelinating neuropathy.

Familial pontocerebellar hypoplasia type I with anterior horn cell disease

We report the association of pontocerebellar hypoplasia and anterior horn cell disease in three female siblings. One child presented with the classical clinical and neuropathological features of pontocerebellar hypoplasia with associated anterior horn cell disease, described by Barth as pontocerebellar hypoplasia type I. This patient showed polyhydramnios, congenital contractures, respiratory insufficiency, hypotonia, areflexia, listlessness and myoclonic seizures. Postmortem examination revealed a loss of neurons and reactive gliosis in the pontocerebellum and in addition anterior horn cell atrophy resembling Werdnig–Hoffmann disease. Another sibling demonstrated the same clinical symptoms. However neuropathological findings showed evidence for pontocerebellar hypoplasia only. The third sibling was examined after induced fetal abortion because of prenatally diagnosed arthrogryposis. Anterior horn cell disease was obvious histologically whereas pontocerebellar hypoplasia could not be demonstrated due to cerebral autolysis. The similar clinical and neuropathological findings in the three reported siblings suggest a common genetic defect with different patterns of pontocerebellar hypoplasia and associated anterior horn cell disease. The gene defect of this rare disorder is still unknown. The ‘survival motor neuron’ gene of spinal muscular atrophy was not found in these three siblings.

A study of cell death in Werdnig Hoffmann disease brain

We examined the occurrence of apoptotic cell death in the autopsied brains of four patients with Werdnig Hoffmann disease (WH), using TdT-mediated in DIG-dUTP nick end labeling (TUNEL) and immunohistochemistry for apoptosis-related proteins. Three of the four patients, aged over 6 months, exhibited TUNEL-positive cells in the lateral nuclei of the thalamus, and one of the three patients also had TUNEL-positive cells in the cerebral cortex. The labeled nuclei did not show characteristic features such as nuclear fragmentation or apoptotic bodies, and synaptophysin-positive granules were observed around some of the TUNEL-positive cells, although none of the antibodies against glial markers could visualize TUNEL-positive cells. TUNEL-positive cells were not observed in other regions examined, including the spinal cord, medulla and cerebellum or in the brains of three age-matched controls. There were neither immunopositive structures for bcl-2 or p53 nor alteration of in situ expression of bcl-xs/l or bax in any subject, and the TUNEL-positive cells lacked immunopositivity against apoptosis-related proteins. The presence of these TUNEL-positive cells might suggest latent neurodegeneration in the thalamus before central chromatolysis of neurons or neuronal loss appears, although it is not clear whether apoptotic cell death is involved in this degenerative process.

Identification and characterization of a mouse homologue of the spinal muscular atrophy-determining gene, survival motor neuron.

Spinal muscular atrophy (SMA), the second most common fatal, autosomal recessive disease of infants, manifests as generalized muscle weakness. The most severe form (Type I, Werdnig-Hoffmann disease) is associated with quadriplegia, respiratory muscle paralysis and death in infancy. Less severe forms are classified as Type II and Type III, based on age of onset and ultimate motor disability. Some spinal motor neurons show chromatolysis and the number of these cells is decreased. Recently, SMA has been mapped to chromosome 5q11.2-13.3 (Gilliam et al., 1990), a region that contains three candidate genes: Survival Motor Neuron (SMN) (Lefebvre et al., 1995); Neuronal Apoptosis Inhibitory Protein (NAIP) (Roy et al., 1995); and p44, a subunit of transcription factor II H (TFIIH) (Carter et al., 1995; Bürglen et al., 1997). Homozygous deletions or deleterious mutations in SMN are present in all SMA patients, and in some affected individuals, deletions have been identified in one or both of the other genes. These extensive deletions may be associated with a more severe phenotype. We have identified and characterized the mouse homologue of SMN, MoSMN, which is 82% identical to SMN at the amino-acid level. Unlike the duplicated human SMN, MoSMN is present in single copy. Like its human counterpart, MoSMN is ubiquitously expressed, but unlike SMN, MoSMN does not appear to be alternatively spliced. In-situ hybridization analysis of the mouse nervous system revealed that MoSMN mRNA is expressed in spinal cord and throughout the brain, with relatively higher levels of expression in the hippocampus and cerebellum.

Electromyography and biopsy correlation with suggested protocol for evaluation of the floppy infant

Eighty infants with nonarthrogrypotic floppy infant syndrome (FIS) were evaluated between 1979 and 1990. Electromyographic data were correlated with results of muscle and nerve biopsies in 41 of 80 who had concomitant biopsies (38) or other diagnostic analyses (3). A diagnosis was made of Werdnig-Hoffmann disease (WHD) in 15, a congenital infantile polyneuropathy (IPN) in 3, neuromuscular transmission defect (NMTD) in 2, myopathy in 12, and presumed "central" hypotonia in 9. A very positive correlation rate between nerve conduction studies with electromyography and biopsy results was found in 93% (14 of 15) with WHD and 100% in IPN (3 of 3). However, only 4 of 10 infants (40%) with biopsy-proven myopathy had an abnormal EMG. Only once did the results of electromyography and biopsy conflict.

The Golgi apparatus of moptor neurons in amyotrophic lateral sclerosis

The Golgi apparatus plays a key role in the posttranslational processing of polypeptides destined for secretion, incorporation into plasma membranes, and fast axoplasmic transport. Dispersion or fragmentation of the Golgi apparatus, experimentally induced by microtubule-disrupting agents, is associated with decreased secretion of immunoglobulins and insulin. The Golgi apparatus is also involved in targeting of lysosomal enzymes and in the endocytosis of certain hormones, receptors, and toxins. There is a paucity of information on this important organelle in human neuropathological conditions. Using an organelle-specific antiserum we have examined by immunocytochemistry the Golgi apparatus of motor neurons in the spinal cord in 4 patients with amyotrophic lateral sclerosis and 1 patient with Werdnig Hoffmann's disease, 1 with infantile neuronal degeneration, 1 with adult-type familial bulbospinal atrophy, 1 with mitochondrial myopathy with cytochrome c oxidase deficiency, 1 with centronuclear myopathy, and 1 with Duchenne's muscular dystrophy, and in 9 age-matched control subjects. In all motor neuronopathies examined and in the patient with mitochondrial myopathy, 20 to 85% of neurons counted had "fragmented" Golgi apparatus. In age-matched control subjects and the other 2 patients with myopathies, 0 to 1.65% of motor neurons had fragmented Golgi apparatus. These findings suggest that the Golgi apparatus of motor neurons is involved in patients with amyotrophic lateral sclerosis and related motor neuron diseases, and perhaps in patients with certain fatal primary myopathies.

High incidence of spinal muscular atrophy type I (Werdnig - Hoffmann disease) in the Karaite community in Israel.

Spinal muscular atrophy (S.M.A.) type I (Infantile werdnig - Hoffmann Disease) was found in 4:1,600 (1:400) infants of the Egyptian Karaite community. This group constitutes a representative sample of the Egyptian Karaite community in Israel, which numbers at present somewhat more than 7,000. The community existed as a religious and reproductive isolate for over 10 centuries. The very high gene frequency, 0.05 for the autosomal recessive gene of S.M.A. type I, is probably the result of genetic drift.

Fetal movements and Werdnig-Hoffmann disease

It has long been known that women bearing a fetus with Werdnig-Hoffmann disease may experience reduced or qualitatively altered fetal movements. This phenomenon has been studied in 56 women who have borne 1 or more infants with this disease. A minimum of one-third of cases of Werdnig- Hoffmann disease are associated with reduced movements in the late third trimester. If present, and interpreted with care, reduced movements in this group of mothers, genetically at risk, are valuable prognostic indicators; as such the phenomenon can be of help in subsequent neonatal and later management. The qualitative changes in such movements are described.