A case of follicular keratosis with trichostasis on an amputated limb.
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Adult↗
Biomedical subjects
M F Jonkman
Publications and source records attributed to M F Jonkman.
Human orf complicated by mucous membrane pemphigoid.
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Anti-Bacterial Agents↗
[Oral pemphigus].
A 33-year-old man suffered from spontaneously developing blisters at the oral mucosa. Firstly, the bullous lesions were observed in the third molar region, but they spread progressively over the buccal and palatal mucosa. The bullous lesions ruptured spontaneously, resulting in erosive lesions and pain. Before being referred to an oral and maxillofacial surgeon, the patient consulted his family doctor, his family dentist, as well as an ear-nose-throat-specialist. The oral and maxillofacial surgeon took a biopsy in order to confirm the clinical diagnosis pemphigus vulgaris. The patient was referred to a dermatologist for treatment with systemic corticosteroids and a non-steroid immunosuppressive drug. Subsequently, the mucosal lesions healed.
Adrenal Cortex Hormones↗
Skin sensitivity to UVB irradiation in systemic lupus erythematosus is not related to the level of apoptosis induction in keratinocytes.
OBJECTIVES: Accumulation of apoptotic cells has been suggested to be involved in the pathogenesis of systemic lupus erythematosus (SLE). As sunlight exposure is one of the factors that can trigger disease activity, we hypothesized that UV light may induce increased numbers of apoptotic cells in SLE. METHODS: Fourteen SLE patients and 16 controls were irradiated with UVB to determine their minimal erythemal dose (MED). Subsequently, skin was irradiated with 1 MED and 2 MED, respectively, and after 24 h skin biopsies were analysed immunohistologically for the number of apoptotic cells and presence of pyknotic nuclear debris. RESULTS: MED was significantly decreased in SLE patients and the presence of decreased MED was associated with a history of butterfly rash. Decreased MED was not related to other skin-related ACR criteria or to autoantibody specificities. No differences were detected in the numbers of apoptotic keratinocytes between patients and controls or in the amount of pyknotic nuclear debris following 1 and 2 MED irradiation, respectively. Absolute UVB doses were correlated with the number of apoptotic keratinocytes; dose-responses did not differ significantly between patients and controls. CONCLUSIONS: Increased sensitivity of SLE patients to UVB, although associated with a history of malar rash, is not related to increased induction of apoptosis or increased levels of secondary necrosis in the skin. Thus, compared with controls, UVB-induced apoptosis is not increased in SLE patients under physiological conditions.
Adult↗
Antiepiligrin cicatricial pemphigoid without mucous membrane involvement.
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Autoantibodies↗
Inflammatory epidermolysis bullosa acquisita with coexistent IgA antibodies to plectin.
We present a case of inflammatory epidermolysis bullosa acquisita (EBA) with IgA antibodies to plectin. Analysis of lesional skin biopsies by electron microscopy revealed the split level to be in the sublamina densa zone, corresponding to the diagnosis of EBA. Direct immunofluorescence of perilesional skin demonstrated u-serrated depositions of IgG and IgA that under immunoelectron microscopy were shown to be located in the sublamina densa. In contrast, indirect immunofluorescence on salt-split skin revealed circulating IgA antibodies that stained the roof rather than the floor of the blister. Immunoblotting showed these serum antibodies to be directed to the cytoplasmic hemidesmosomal antigen plectin. The antiplectin specificity of these antibodies was confirmed by 'knockout' immunofluorescence analysis; the serum IgA did not bind to skin sections of a patient with plectin-deficient epidermolysis bullosa. To our knowledge, this case demonstrates for the first time the existence of IgA antibodies against plectin.
Aged↗
Life-long course and molecular characterization of the original Dutch family with epidermolysis bullosa simplex with muscular dystrophy due to a homozygous novel plectin point mutation.
Plectin is one of the largest and most versatile cytolinker proteins known. Cloned and sequenced in 1991, it was later shown to have nonsense mutations in recessive epidermolysis bullosa with muscular dystrophy. A dominant mutation in the gene was found to cause epidermolysis bullosa simplex Ogna without muscular dystrophy. Here we report the DNA sequencing of the plectin gene (PLEC1) in a Dutch family originally described in 1972 as having epidermolysis bullosa with muscular dystrophy. The results revealed homozygosity for a new plectin nonsense mutation at position 13187 and its specific 8q24 marker haplotype profile. Western blotting of cultured fibroblasts and immunofluorescence microscopy of skin biopsy confirm that the plectin protein expression is grossly reduced or absent. A summary of the life-long clinical course of the two affected brothers homozygous for the new E1914X mutation is given.
Base Sequence↗
Follicular non-Hodgkin's lymphoma with refractory paraneoplastic pemphigus: case report with review of novel treatment modalities.
In this paper a patient with a non-Hodgkin's lymphoma (NHL) and paraneoplastic pemphigus (PNP) is described. PNP is a very rare, painful mucocutaneous intraepithelial blistering disease associated with occult or confirmed malignancy. Patients with PNP show severe, progressive mucocutaneous disease with a high mortality rate, because of drug-induced infectious complications. The patients sometimes benefit from high doses of oral corticosteroids. However, pulse therapy with high doses of prednisolone (or dexamethasone) in combination with other immunosuppressants induces variable and inconstant results. Intravenous immunoglobulin (IVIg) has been applied in different cases of PNP with encouraging results. Plasmapheresis or plasma exchange (PE) in combination with corticosteroids and/or cyclophosphamide or azathioprine showed similar rapid and beneficial results in association with decreasing auto-antibody levels in this group of refractory pemphigus. Another interesting therapeutic option is rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, which is found on the surface of normal and malignant B-lymphocytes. Administration of rituximab for patients with PNP in combination with follicular NHL is not always successful regarding oral lesions as we report in this case. PE leading to prompt depletion of autoreactive antibodies combined with immunosuppressants or synchronisation of PE with IVIg seems the best treatment modality for this refractory group, but the therapeutic value and appropriate timing of rituximab obviously deserve further evaluation in patients with low grade NHL and PNP.
Adrenal Cortex Hormones↗
A very mild form of non-Herlitz junctional epidermolysis bullosa: BP180 rescue by outsplicing of mutated exon 30 coding for the COL15 domain.
Mutations in the gene COL17A1 cause non-Herlitz junctional epidermolysis bullosa. Here, we describe a patient who, despite two heterozygous mutations in COL17A1, has an extremely mild form of the disease missing most of the characteristic clinical features. DNA analysis revealed a frame-shift mutation 3432delT and a nonsense mutation 2356C-->T (Q751X). cDNA analysis showed that the deleterious effect of the latter mutation was skirted by deleting the premature termination codon containing exon 30. In this way, the reading frame was restored, resulting in a 36 nucleotides shorter mRNA transcript. Immunoblot analysis showed expression of the 180-kDa bullous pemphigoid antigen (BP180) with a slightly higher SDS-PAGE mobility, in line with the deletion of 12 amino acids from the COL15 domain. Immunofluorescence of skin sections showed diminished, but correctly localised expression of BP180, and this, in concert with the mild clinical phenotype, suggests that this COL15 mutated BP180 is still partly functional.
Autoantigens↗
U-serrated immunodeposition pattern differentiates type VII collagen targeting bullous diseases from other subepidermal bullous autoimmune diseases.
BACKGROUND: Epidermolysis bullosa acquisita (EBA) can be differentiated from other subepidermal bullous diseases by sophisticated techniques such as immunoelectron microscopy, salt-split skin antigen mapping, fluorescence overlay antigen mapping, immunoblot and enzyme-linked immunosorbent assay. OBJECTIVES: To determine whether the diagnosis can also be made by routine direct immunofluorescence microscopy. METHODS: We studied frozen skin biopsies from 157 patients with various subepidermal immunobullous diseases. RESULTS: We found three distinct 'linear' fluorescence patterns at the basement membrane zone: true linear, n-serrated and u-serrated. The true linear pattern, often seen in conjunction with either the n- or the u-serrated pattern, was found in any subepidermal immunobullous disease with nongranular depositions. In bullous pemphigoid, mucous membrane pemphigoid, antiepiligrin cicatricial pemphigoid, p200 pemphigoid and linear IgA disease the n-serrated pattern was found, corresponding with depositions located in hemidesmosomes, lamina lucida or lamina densa. However, in EBA and bullous systemic lupus erythematosus the u-serrated staining pattern was seen, corresponding with the ultralocalization of type VII collagen in the sublamina densa zone. The diagnosis of EBA with IgG or IgA autoantibodies directed against type VII collagen was confirmed by immunoelectron microscopy, salt-split skin antigen mapping, fluorescence overlay antigen mapping or immunoblotting. CONCLUSIONS: Using this pattern recognition by direct immunofluorescence microscopy we discovered several cases of EBA which would otherwise have been erroneously diagnosed as a form of pemphigoid or linear IgA disease.
Basement Membrane↗
Features of epidermolysis bullosa simplex due to mutations in the ectodomain of type XVII collagen.
BACKGROUND: Mutations in COL17A1, coding for type XVII collagen, cause junctional epidermolysis bullosa with an ultrastructural plane of cleavage through the lamina lucida of the epidermal basement membrane. OBJECTIVES: To identify the COL17A1 mutations in a child with reduced type XVII collagen expression and intraepidermal blister formation. PATIENT AND METHODS: Protein expression and level of tissue separation were studied by immunofluorescence and electron microscopy. The mutations were identified by analysing the patient's DNA and mRNA. RESULTS: Immunofluorescence microscopy performed on nonlesional skin demonstrated absence of the type XVII collagen endodomain and presence, although reduced, of the shed ectodomain. Electron microscopy showed that the plane of cleavage was through the basal cells, not through the lamina lucida. Two heterozygous mutations were identified in COL17A1: a new 3'-acceptor splice-site mutation in intron 21 (1877-2A-->C), and a deletion in exon 48 (3432delT). The splice-site mutation in intron 21 results in alternative transcripts of which two are in-frame, with deletions of the first nine codons of exon 22 and the entire exon 22, respectively. By Western blot analysis, a type XVII collagen molecule was detected that was slightly smaller than normal. CONCLUSIONS: Occasionally mutations in the COL17A1 gene may result in split levels suggesting epidermolysis bullosa simplex rather than junctional epidermolysis bullosa.
Autoantigens↗
[From gene to disease; epidermolysis bullosa due to mutations in proteins in or around the hemidesmosome].
Epidermolysis bullosa is a group of hereditary mechanobullous dermatoses in which detachment of the skin and mucosa in or around the epidermal basement membrane takes place from birth on. The clinical manifestations vary from abnormalities in the nails to painful mutilation of the skin, eyes, mouth, throat, oesophagus and locomotor apparatus. Ten genes have been identified that can cause a form of epidermolysis bullosa. These genes code for proteins in or around the hemidesmosome, the site of anchorage of the basal cell to the basement membrane. The prevalence of epidermolysis bullosa is about 1 in 22,000. The diagnosis is on the basis of the medical history, clinical findings, immunofluorescence microscopy, electron microscopy and DNA studies. The current treatment is still primarily symptomatic and prophylactic.
Basement Membrane↗
Natural repair mechanisms in correcting pathogenic mutations in inherited skin disorders.
This review assesses molecular aspects of the rescue of disease-causing mutations in genodermatoses by means of naturally occurring secondary genetic phenomena. Such data have important implications for the design of gene therapy approaches for inherited skin diseases. Reversal of the phenotype depends on three elements: the number of cells involved; the degree of gene reversal; and the specific timing of the reversion. If reversion occurs in somatic cells, revertant mosaicism may occur. This is the situation in which a patient's skin is generally affected by the genodermatosis, but islands of normal skin stand out. These reflect the presence of revertant cells that are sufficient to restore a normal local skin phenotype. Reversion of the original mutation may also be partial, in which case the phenotype may display no, or only limited, improvement. Nevertheless, the phenotype may ameliorate with age if the reverted cells preferentially expand in time or if the time of onset of reversion is after birth. In essence, the complexities of naturally occurring rescue processes are important to understand because the inherent mechanisms may provide clues and insight into optimal therapeutic gene manipulation, and the possibility of mimicking nature in the management of patients with diverse genodermatoses.
Frameshift Mutation↗
Bullous eosinophilic cellulitis (Wells' syndrome) associated with Churg-Strauss syndrome.
We report a patient with Churg-Strauss syndrome (CSS) with asthma, eosinophilia, nasal polyposis and ANCA-associated multisystem vasculitis, who's skin eruption started with erythematous urticarial-plaques followed by haemorrhagic bullae. Histology of the plaques revealed 'flame figures' in the dermis with no granulomatous or vasculitic process, consistent with the diagnosis of eosinophilic cellulitis or Wells' syndrome. The association of CSS and Wells' syndrome observed in this patient may have a common pathogenesis. CSS may induce Wells' syndrome by an unknown factor.
Cellulitis↗
[Spontaneous blood blister formation swellings of the oral mucosa].
An 88 year-old man was hospitalized because of bullous pemphigoid of the skin with detectable autoantibodies against type XVII collagen. During his stay in the hospital, he developed easily bleeding hemorrhagic bullous lesions of the oral mucosa, which were thought to be an oral manifestation of bullous pemphigoid. A thorough blood examination showed acquired haemophilia A, related to the development of autoantibodies against factor VIII.
Aged↗
Dexamethasone pulse therapy in pemphigus.
Pulse therapy with high-dose glucocorticoids was introduced 20 years ago as a treatment modality for autoimmune disease and transplant rejection. The most popular dermatological indication for pulse therapy is severe pemphigus. We reviewed the sequelae of 14 patients with pemphigus who were treated by pulse therapy. Seven of them reached complete remission, although three of them needed a new pulse course due to disease flare-up. Adverse events were minor and confined to 60% of all patients: temporary facial flushing during pulse administration, sleep disturbances during the first night after pulse administration, and mood changes occurred during the week of pulse therapy. The study showed the possibility of oral instead of an intravenous mute of dexamethasone pulse administration, which makes double-blind placebo-controlled trials ethically feasible. Fifty per cent of the patients reached complete remission. This retrospective study does not allow claims on the steroid-sparing effect.
Anti-Inflammatory Agents↗
Persistent failures in gene repair.
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Animals↗
Truncated typeXVII collagen expression in a patient with non-herlitz junctional epidermolysis bullosa caused by a homozygous splice-site mutation.
SUMMARY: Type XVII collagen (180-kDa bullous pemphigoid antigen) is a structural component of hemidesmosomes. Mutations in the type XVII collagen gene (COL17A1) have been established to be the molecular basis of non-Herlitz junctional epidermolysis bullosa (JEB-nH), an inherited skin blistering disorder. Here we report for the first time truncated type XVII collagen expression, caused by homozygosity for a COL17A1 donor splice-site mutation (4261+1 g --> c), which was identified by PCR amplification on genomic DNA. By RT-PCR and sequencing of cDNA derived from mRNA from the patient's cultured keratinocytes, we provide evidence of cryptic splicing and exon skipping, most abundantly of exon 52. JEB-nH patients with COL17A1 splice-site mutations resulting in an exon skip often have no immunologically detectable type XVII collagen. However, in our patient with the generalized atrophic benign epidermolysis bullosa subtype, a small amount of type XVII collagen was detectable in the skin, and immunoblotting of cultured keratinocytes revealed that the 180-kDa protein was 10 kDa shorter. We hypothesize that the function of this truncated type XVII collagen polypeptide, which is expressed at low levels, is impaired, explaining the JEB-nH phenotype.
Aged↗