Mutations in PIGB Cause an Inherited GPI Biosynthesis Defect with an Axonal Neuropathy and Metabolic Abnormality in Severe Cases.

Proteins anchored to the cell surface via glycosylphosphatidylinositol (GPI) play various key roles in the human body, particularly in development and neurogenesis. As such, many developmental disorders are caused by mutations in genes involved in the GPI biosynthesis and remodeling pathway. We describe ten unrelated families with bi-allelic mutations in PIGB, a gene that encodes phosphatidylinositol glycan class B, which transfers the third mannose to the GPI. Ten different PIGB variants were found in these individuals. Flow cytometric analysis of blood cells and fibroblasts from the affected individuals showed decreased cell surface presence of GPI-anchored proteins. Most of the affected individuals have global developmental and/or intellectual delay, all had seizures, two had polymicrogyria, and four had a peripheral neuropathy. Eight children passed away before four years old. Two of them had a clinical diagnosis of DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures), a condition that includes sensorineural deafness, shortened terminal phalanges with small finger and toenails, intellectual disability, and seizures; this condition overlaps with the severe phenotypes associated with inherited GPI deficiency. Most individuals tested showed elevated alkaline phosphatase, which is a characteristic of the inherited GPI deficiency but not DOORS syndrome. It is notable that two severely affected individuals showed 2-oxoglutaric aciduria, which can be seen in DOORS syndrome, suggesting that severe cases of inherited GPI deficiency and DOORS syndrome might share some molecular pathway disruptions.

Toenail abnormalities in rheumatoid arthritis patients are associated with radiographic damage and impact disability: a cross sectional study nested within a cohort.

OBJECTIVES: Cutaneous involvement is an extra-articular manifestation of rheumatoid arthritis (RA). This includes nail abnormalities, which are often overlooked. We described nail findings in RA patients currently attending an early arthritis cohort (n=145), and associated them with disease activity and/or damage, as well as patient-reported outcomes. METHODS: A standardised nail examination was performed in 122 patients (84.1% of the cohort), concomitant to the rheumatic assessment. Disability, quality of life and perceived nail-related health were also assessed. Nail findings and their location were recorded and classified according to standardised definitions. Logistic and linear regression models were used to investigate predictors of nail findings and to identify the impact of toenail findings on disability, which was evaluated with the HAQ. Patients consented to participate. RESULTS: Patients were primarily middle-aged females, with median follow-up of 9 years, and had disease under control. Most patients (62.3%) had at least one nail finding and these patients scored lower their nail-related health. The median (IQR) of findings/abnormalities per patient was 3 (2-5) and the number of nails affected per patient was 10 (2-12). Age (OR: 1.04, 95%CI: 1.007-1.074) and erosive disease (OR: 2.26, 95%CI: 1.1-5.1) were associated with nail findings. Toenail involvement was consistently associated with HAQ score out of normal range (OR=3.4, 95%CI=1.24-9.35, p=0.02). There was a linear association between the number of toenails affected and the HAQ score. CONCLUSIONS: Nail abnormalities are common and heterogeneous findings in RA patients; they are associated with erosive damage and impact disability.

Distal nail embedding treatment using autogenous nails.

A regrowing nail tip after nail avulsion may excessively curve and invaginate into the nail bed. This is treated as a type of ingrown toenail, and is known as distal nail embedding. In most cases, further growth restores the original shape evenly over the nail bed. However, it is often painful and such cases may require treatment. We report a surgical approach that we applied to six cases of distal nail embedding involving pain or deformity of nails caused by a nail tip invaginating into the nail bed and/or cessation of forward nail growth. As our method involves removing a portion of the embedded tip edge nail and inserting the removed nail into the remaining depressed portion, the nail can grow over the bulge. In all six patients in whom we applied this method, the pain and nail deformity resolved and there was no recurrence. We used autogenous nails, which can reduce the pressure imbalance on a nail bed, and this contributed to improving the morphology of nails and nail beds. In addition, the risk of a hypertrophied nail is reduced because half of the nail adheres to the nail bed. Special materials are unnecessary and this method can be conducted with simple outpatient department procedures. There were no cases of a fixed nail section detaching due to a bulge at the nail tip. The inserted nail was maintained in all cases for several months until the nail grew over the bulge.

Posttraumatic onychoheterotopia: A case and review of the pediatric literature.

BACKGROUND: Onychoheterotopia, or ectopic nail, is a rare nail condition in which nail growth occurs in areas other than the distal phalanges. The majority of cases in the literature are noted to be congenital; however, acquired cases have less commonly been described following either acute or chronic trauma. METHODS: We present a case of acquired onychoheterotopia in a child, with a corresponding literature review of acquired pediatric onychoheterotopia cases for comparison. RESULTS: There were a total of 10 cases of acquired onychoheterotopia in pediatric patients in the literature. Including our patient, 81.8% (9/11) developed an ectopic nail on the fingers. Crush injury preceded the ectopic nails in 45.5 % (5/11) of cases. Infection occurred in 27.3% (3/11). CONCLUSIONS: Although the incidence and prevalence of acquired onychoheterotopia are unknown, it seems to be an uncommon phenomenon. From our case and others from the literature, there may be associations with crush injury specifically. Further research will be needed to fully elucidate the pathophysiology and risk factors for ectopic nail growth.

Congenital malalignment of the great toenail: Conservative and definitive treatment.

Congenital malalignment of the great toenail, or ungual malalignment, is a rarely recognized disorder. It is characterized by lateral deviation of the longitudinal axis of the nail plate with respect to the distal phalanx, and if untreated, complications in the late teens and adulthood may arise. In this study, we have reviewed conservative and definitive treatments for this disorder.

Carpal tunnel syndrome and associated nail changes: Review and examples from the author's practice.

Carpal tunnel syndrome (CTS) is commonly seen by general practitioners and often presents with neurologic symptoms of nocturnal pain and paresthesia along the median nerve distribution. Approximately 20% of patients also present with cutaneous findings (ulcerations, blistering, sclerodactyly, nail dystrophy) characterizing a severe form called necrotic CTS. Necrotic CTS can also be associated with bone changes (acro-osteolysis). In the author's practice, combined nail and skin findings are not an uncommon presentation of CTS, although this form remains overlooked and underreported in the dermatological textbooks and studies. This manuscript aims to review the literature on CTS cases, with a specific focus on using associated nail findings as diagnostic clues. The literature review along with a few additional recent cases from the author's practice demonstrate that CTS is frequently accompanied by a variety of nail changes including koilonychia, longitudinal fissuring, Beau's lines, onychomadesis, melanonychia, nail thickening, hyperkeratosis, and ischemic ulcerations with paronychia. Furthermore, when these changes are limited to the second and third fingernails, they should prompt the diagnosis of CTS. Once suspected, diagnostic evaluation is not difficult and surgical management can resolve cutaneous findings and prevent irreversible changes such as acro-osteolysis.

Nail abnormalities identified in an ageing study of 30 inbred mouse strains.

In a large-scale ageing study, 30 inbred mouse strains were systematically screened for histologic evidence of lesions in all organ systems. Ten strains were diagnosed with similar nail abnormalities. The highest frequency was noted in NON/ShiLtJ mice. Lesions identified fell into two main categories: acute to chronic penetration of the third phalangeal bone through the hyponychium with associated inflammation and bone remodelling or metaplasia of the nail matrix and nail bed associated with severe orthokeratotic hyperkeratosis replacing the nail plate. Penetration of the distal phalanx through the hyponychium appeared to be the initiating feature resulting in nail abnormalities. The accompanying acute to subacute inflammatory response was associated with osteolysis of the distal phalanx. Evaluation of young NON/ShiLtJ mice revealed that these lesions were not often found, or affected only one digit. The only other nail unit abnormality identified was sporadic subungual epidermoid inclusion cysts which closely resembled similar lesions in human patients. These abnormalities, being age-related developments, may have contributed to weight loss due to impacts upon feeding and should be a consideration for future research due to the potential to interact with other experimental factors in ageing studies using the affected strains of mice.

Onychoscopy of non-infectious nail abnormalities in patients after allogeneic haematopoietic stem cell transplantation.

Nail abnormalities after allogeneic haematopoietic stem cell transplantation procedure (alloHSCT) are often reported. Usually, they are related to chronic graft-versus-host disease (cGvHD). So far, only clinical manifestations of selected nail abnormalities have been described, without the presentation of dermoscopic images. In this article, we present morphologic and dermoscopic manifestations of potential non-infectious nail abnormalities in patients after alloHSCT procedure based on reviewed literature and our own experience with dermoscopic iconography. In majority of studies published till now, nail changes are not connected to severity of other cGvHD symptoms; however, e.g. the presence of pterygium inversum unguis may be an indicator of lung dysfunction. As nail changes may be an early sign of cGvHD and always present in association with other manifestations, routine clinical assessment should include nails examination. Knowledge of possible presentation of nail involvement after alloHSCT may be valuable for treating physician.

A comparative study of onychomycosis and traumatic toenail onychodystrophy dermoscopic patterns.

BACKGROUND: Onychomycosis (OM) and traumatic onychodystrophy (OD) are common causes of toenail changes. A clinical diagnosis is often impossible without mycology. Dermoscopy is helpful in this setting but yet underexplored. Prospective comparative studies between OM and OD onychoscopic findings have not been previously performed. OBJECTIVES: We sought to determine distinguishing dermoscopic presentations of OM and traumatic OD. METHODS: We performed a prospective, observational study including patients presenting with ≥1 toenail onychodystrophy. All underwent onychoscopy, clinical and mycological examination. Based on these results, patients received a final diagnosis of OM or OD. Dermoscopic presentations of OM and OD patients were classified in patterns and compared. RESULTS: In all, 110 cases of OM and 82 of traumatic OD were compared. Statistical analyses revealed that the distal pulverized and the irregular spiked macular dermoscopic patterns were predictors of an OM diagnosis. The regular macular, the non-classifiable, the total and partial homogeneous background dermoscopic patterns correlated with traumatic OD diagnosis. CONCLUSIONS: We demonstrated that OM and traumatic OD have distinctive onychoscopic presentations. Dermoscopy may be an important ancillary tool to guide their differential.

Nail Changes in Sézary Syndrome: A Single-Center Study and Review of the Literature.

BACKGROUND: The onychodystrophies associated with Sézary syndrome (SzS) have rarely been described in the literature. We performed a retrospective analysis of SzS patients at a single institution and compared our data with previous publications. OBJECTIVES: The objectives of this study were to identify and describe the most frequent nail alterations in patients with SzS. METHODS: A retrospective analysis was performed with some prospective observations at the University of Pittsburgh from 1989 to 2017. RESULTS: We identified 54 patients with SzS out of 535 patients with cutaneous T-cell lymphoma. Nineteen patients with SzS had photos of their nail. All those patients exhibited some type of onychodystrophy. The most common types were paronychia (63.2%; 12/19), leukonychia (42.1%; 8/19), onycholysis (42.1%; 8/19), trachyonychia (31.6%; 6/19), and subungual hyperkeratosis (26.3; 5/19). Cluster analysis of our data in comparison with published data on the psoriatic nails indicated that while leukonychia, onycholysis, subungual hyperkeratosis, and nail discoloration were frequently observed in psoriasis, onychauxis, anonychia, distal notching, and onychoschizia occurred more commonly in patients with SzS. CONCLUSIONS: The most common nail manifestations in SzS patients included paronychia, leukonychia, and onycholysis. The nail manifestations in SzS patients appeared to be heterogeneous, while onychauxis, anonychia, distal notching, and onychoschizia seem to be specific to SzS in comparison with psoriasis.

A rare disease with a rare presentation: hemi-atrophy caused by fibromuscular dysplasia in a 27 month old girl.

We discuss the case of a 27-month-old girl afflicted with fibromuscular dysplasia. She presented with hemiatrophy of left upper and lower limbs, nail dystrophy, ulcers on the tips of her toes, cold and painful limbs, foot drop, and hypertension. The initial appearance started at 2 months of age and other diagnoses such as complex regional pain syndrome, reflex sympathetic syndrome, vasculitis and coagulation disorders had been considered. Angiography revealed that all the arterial branches of the left lower and upper limbs, from brachial to ulnar and radial, and from iliac and femoral to tibialis arteries were affected. Sural nerve biopsy confirmed the diagnosis. In the follow-up visits until 2 years after the patient's discharge she did not develop any new problem and her blood pressure was controlled by enalapril and amlodipine.

A rare case of skin blistering and esophageal stenosis in the course of epidermolysis bullosa - case report and literature review.

BACKGROUND: Epidermolysis bullosa (EB) constitutes a heterogenous group of rare multisystem genetically transmitted disorders comprising several blistering muco-cutaneous diseases with a monogenic basis and either autosomal dominant or autosomal recessive mode of inheritance. EB manifestation is not only limited to the skin. Systemic signs might involve the nose, ear, eye, genitourinary tract and upper gastrointestinal tract. The presence of particular symptoms is directly determined by a type of altered skin protein. Gastrointestinal manifestation of EB is most commonly reflected by esophageal stenosis due to recurrent esophageal blistering, followed by consequent scarring. CASE PRESENTATION: Here we present a case of a man with dystrophic EB and dysphagia, skin blistering, joints contractures and missing nails. To our knowledge, the presented man is the oldest one diagnosed with EB living in Poland. CONCLUSIONS: Management of an esophageal stricture in such circumstances is based on endoscopic dilatation. However, in most severe cases, placement of a gastrostomy tube is required. Despite great advances in medicine, a targeted therapy in the course of EB has not been established yet.

Pincer nail in a lupus patient.

Pincer nail is a transverse overcurvature of the nail plate that may appear in association with a variable number of diseases. We present a case report of a 28-year-old woman with pincer nail deformity associated with systemic lupus erythematosus. A renal biopsy confirmed class V lupus nephritis and treatment had included systemic steroids and cyclophosphamide. After 6 months there was a marked improvement of nail deformities.

Median canaliform dystrophy of Heller after cryotherapy.

Cryotherapy, widely used in the treatment of common warts, can cause long-term side effects when used in the treatment of warts near the nail bed. Here we present the case of a 11-year-old girl who developed canaliform dystrophy and long-term hypopigmentation following cryotherapy of warts on the proximal nail folds.