Expanding the clinical features of autoinflammation and phospholipase Cγ2-associated antibody deficiency and immune dysregulation by description of a novel patient.

BACKGROUND: Autoinflammation and phospholipase Cγ2-associated antibody deficiency and immune dysregulation (APLAID) is an exceedingly rare monogenic autoinflammatory disease. To date, only five cases have been reported with four distinct pathogenic mutations. OBJECTIVES: We present a novel case of APLAID, corroborated by molecular analysis, with newly described clinical findings including central nervous system vasculitis (CNSV); and distinctive histopathological characteristics that may expand our knowledge of this rare disease's phenotype. METHODS: This is a case report presentation of a 3-year-old boy, seen at a reference paediatric hospital in Mexico. His parents authorized the use of his clinical information and photographs. RESULTS: A 3-day-old boy presented to the emergency department with a vesiculo-pustular rash that resolved within 1 week. Two months later, he developed widespread papules and pseudovesicles that evolved into infiltrated plaques. He also had periodical flares of conjunctivitis, diarrhoea and erythematous blistering acral plaques triggered by upper respiratory infections. By the age of 10 months, he experienced seizures and CNSV. Laboratory work-up showed mild neutropenia, decreased serum levels of immunoglobulins and B-cell lymphopenia. A skin biopsy revealed a dense, perivascular and interstitial histiocytic and granulomatous infiltrate, with palisading granulomas, and leucocytoclastic vasculitis with karyorrhexis. APLAID syndrome was confirmed by Sanger sequencing of PLCG2 gene [heterozygous genotype LRG_376t1:c.2543T>C or p.(Leu848Pro)]. CONCLUSIONS: Presence of CNSV has not been previously described in APLAID, however as the number of reported patients with APLAID is very small, it is possible that the overall spectrum of clinical manifestations has not been completely elucidated. The herein identified p.(Leu848Pro) variant was also documented in a Portuguese patient, suggesting that it could be a PLCG2 gene 'hot-spot'.

Subcutaneous immunoglobulin for the treatment of deep morphoea in a child.

Morphoea, also known as localized scleroderma, is a disorder characterized by excessive collagen deposition leading to thickening of the dermis and/or subcutaneous tissues. Intravenous IgG therapy has induced improvement in some fibrotic conditions. The primary indication for subcutaneous IgG (SCIG) is in primary immunodeficiency disorders as replacement therapy; however, recently there has been considerable interest in SCIG as an immunomodulatory agent. We report an 11-year-old girl with deep morphoea who was successfully treated with SCIG.

Treatment of 18 children with scabies or cutaneous larva migrans using ivermectin.

In addition to onchocerciasis and other filarial diseases, ivermectin has been used for the treatment of scabies, head lice, larva migrans and gnathostomiasis. However, there is concern regarding the safety of its use in children under 5 years of age or weighing less than 15 kg. We present our experience in 18 children (aged 14 months to 17 years), with scabies or cutaneous larva migrans successfully treated with ivermectin. They included four cases of crusted scabies associated with immunosuppression and seven cases of common scabies four of whom had associated clinical mental retardation, immunosuppression or hypomobility. A further seven patients had cutaneous larva migrans. Fifteen patients were cured with a single dose of ivermectin, and three patients with crusted scabies required a second dose. None of our patients suffered significant adverse effects. We believe that ivermectin is a safe and effective alternative treatment of cutaneous parasitosis in children.

Frequency of toenail onychomycosis in patients with cutaneous manifestations of chronic venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) can originate onychopathy per se. We have anecdotally observed nail changes in patients with CVI, but there are few studies which determine the frequency of both onychopathy and onychomycosis in these patients OBJECTIVE: The aim of the study was to determine the frequency of nail pathology and onychomycosis in patients with CVI PATIENTS AND METHODS: We included 36 adult patients, both men and women, aged from 18 to 59 years, with clinically documented venous leg ulcers. All patients were examined by a dermatologist and the venous leg ulcers were classified according to severity in three grades. The nail changes were described and a mycological examination was performed. We obtained a small fragment of the nail for histological examination. In 27 patients, we also performed functional studies to determine the type of venous insufficiency. RESULTS: The ratio of women to men was 5 : 1. The mean age of patients was 46.39 +/- 8.51 years, men being slightly younger than women. Ten patients had ulcers of grade I severity, 12 had grade II, and 14 had grade III. The overall time of evolution of the cutaneous lesions was 11.02 +/- 10.11. Fourteen patients had superficial venous insufficiency, whereas 13 had deep venous insufficiency. Twenty-two (61.11%) of our patients had nail alterations. These nail changes were related more to the type of vascular affection than with the severity of cutaneous involvement. In more than half of the cases (59.09%), onychomycosis was the cause of the nail changes. The overall frequency of onychomycosis was 36.11%. The etiologic agent of onychomycosis was isolated in 38.46% of the cases, and Trichophyton rubrum was the most frequent agent. The histologic examination of the nail plate showed a low sensitivity (62%) but a high specificity (100%) in the detection of nail plate parasitization. No clinical differences could be established between the nail changes observed in patients with true onychomycosis and those with nonfungal onychopathy. CONCLUSIONS: Nail changes are common in patients with venous leg ulcer, and onychomycosis accounts for slightly more than half of the cases. We therefore recommend a routine mycological examination in patients wit nail changes and cutaneous manifestations of CVI, to diagnose or rule out onychomycosis, and therefore avoid overtreating patients without onychomycosis with antimycotics.

Angiosarcoma of the scalp.

An 82-year-old woman was seen at our Dermatology Department for a plaque on the right parietal scalp that had recently increased in size, and bled. The lesion had been present for 3 months. The patient had a previous diagnosis of chronic bronchitis, noninsulin-dependent diabetes mellitus, and hypertension, but no previous history of cancer. Physical examination revealed a 7 x 10 cm plaque, composed of a central necrotic and bleeding surface, surrounded by small purple-red satellite nodules. A biopsy showed an ill-defined infiltrative intradermal mass with a pattern of hypercellular sheets of large cells alternating with areas of dilated, irregular, blood-filled channels, dissecting the collagen bundles. The endothelial cells lining these channels were plump and pleomorphic, surrounded by other spindle-shaped cells with pleomorphic and atypical nuclei. The diagnosis of angiosarcoma was made, and the patient was sent to an oncology center for further evaluation and treatment, where a computed tomography head scan was taken revealing no erosion of the skull. The patient refused surgery, so radiotherapy was proposed. One month later, she developed lymph node enlargement of the left anterior cervical nodes. A needle aspiration biopsy was consistent with sarcoma. Two weeks later, she was started on palliative radiotherapy: a programmed dose of 4500 cGy was proposed of which she only received 3000 cGy because of treatment withdrawal and loss to follow-up. During this time, she showed partial initial response, but despite treatment the disease relentlessly progressed, with hemorrhage and severe pain being the most striking features.

Thalamic vascular lesions. Risk factors and clinical course for infarcts and hemorrhages.

BACKGROUND AND PURPOSE: The data of patients with an MRI-confirmed diagnosis of thalamic stroke were analyzed to identify risk factors and to describe the clinical syndromes according to the thalamic arterial territory involved. METHODS: We examined the records of all patients with a diagnosis of thalamic stroke confirmed by MRI who attended the National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez" from 1987 through 1995. A database containing demographic features, risk factors, clinical course, type and mechanism of stroke, and vascular territory was analyzed. RESULTS: Twenty-eight patients (19 men and 9 women; mean age, 48.2 years) had MRI-confirmed thalamic stroke. Infarct was present in 22 patients and hemorrhage in 6. Eleven (39.3%) patients were younger than 45 years. In these young patients, cigarette smoking was the main risk factor associated with the development of stroke. In young patients, isolated and multiple thalamic lesions were present in almost equal proportions. The remaining 17 patients were older adults (45 to 84 years of age). In such patients, most lesions were multiple and were associated with atherosclerosis-predisposing factors. The main distinguishing clinical feature for hemorrhages and paramedian infarcts in comparison with infarcts in the other thalamic territories was the presence of an altered level of consciousness. No patient died as a direct result of the stroke. CONCLUSIONS: Thalamic stroke commonly occurs in young adults. and its mechanism is often undetermined. Increased awareness of this type of stroke in young adults should lead to better delineation of its clinical features, course, and management.