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Congenital (non-bullous) ichthyosis is a rare group of keratinizing disorders which can be tentatively subclassified based on clinical criteria, analysis of transglutaminase 1 gene mutations and electron microscopy of epidermis. We studied 83 patients who were all on topical therapy and in 16 cases also on oral retinoids. Three main groups of patients were distinguished: (A) those with transglutaminase 1 gene mutations (n=44), (B) those without transglutaminase 1 gene mutations showing a coarse, generalized scaling (n=19), and (C) those without transglutaminase 1 gene mutations showing only fine or focal scaling (n=20). On clinical scoring, patients in group A were more hyperkeratotic and less erythematous than those in group B (p < 0.05). Anhidrosis was recorded in nearly all patients (> or = 80%), but ectropion and a collodion phenotype at birth were more common in group A versus other groups. Ultrastructurally, a high frequency of type I (Anton-Lamprecht's classification) was found in all three groups (37-63%), 20 cases of type II in group A and a few cases of types III and IV in groups B and C, respectively. In conclusion, transglutaminase 1 gene mutation is a major cause of congenital ichthyosis in Sweden and Estonia, and is often associated with severe scaling and ultrastructural type II in corneocytes. The transglutaminase-unrelated cases are more heterogeneous, probably reflecting a more varied aetiology.

Congenital ichthyoses are a group of heterogeneous disorders of cornification. Autosomal recessive congenital ichthyosis (ARCI) can be clinically subdivided into congenital ichthyosiform erythroderma and lamellar ichthyosis. Ultrastructurally, ARCI is classified into four groups: ichthyosis congenita (IC) types I-IV. The genetic background of the ARCI disorders is heterogeneous, but only one disease gene, transglutaminase 1, has been detected so far. We describe six patients with severe congenital ichthyosis from six different Scandinavian families. They could not be classified ultrastructurally into the four IC groups because of atypical findings of electron microscopy. These included abnormal lamellar bodies, alterations in keratohyalin, remnant organelles and lipid inclusions in the upper epidermal cells, which resembled the ultrastructural findings of harlequin ichthyosis (HI), although the HI phenotype was not present at birth. Some clinical features, such as thick scales, erythroderma, alopecia and ectropion were common to all patients. Ichthyosis was usually accentuated in the scalp and four patients had clumped fingers and toes. None of the patients carried the transglutaminase 1 mutation. We conclude that ultrastructural findings resembling those detected in previous HI cases (type 1 and 2) can also be found in patients who do not have classic clinical features of that rare ichthyosis. This may be due to lack of specificity of ultrastructural markers for HI or to its clinical heterogeneity.

Background: Erythropoietic protoporphyria (EPP) is an inherited disease caused by deficient activity of ferrochelatase in the heme biosynthetic pathway. Accumulation of protoporphyrins and light exposure results in acute phototoxic skin reactions. The histopathologic findings of the light-exposed skin are thickening of the superficial dermal vessel walls and amorphous deposits around the vessels, but the origin and detailed composition of the perivascular material have been unclear., Objective: The vascular morphology and composition of the perivascular material were studied in the skin samples of patients with EPP., Methods: Skin biopsy specimens of 8 patients with EPP representing 7 Finnish EPP families with different genotypes were studied by means of light and electron microscopy and immunohistochemical methods., Results: The characteristic finding was thickened, periodic acid-Schiff-positive vessel walls caused by concentric reduplication of basal lamina and excess of fine granular material at the basal membrane zone in the superficial dermis. The perivascular deposits in the vicinity of vessel walls had a homogeneous or fine granular appearance without filaments. Direct immunofluorescence showed constant IgG deposits together with IgA, IgM, and C3 in the vessel walls. In immunohistochemistry, collagen IV and laminin could be demonstrated at the vascular basal membrane together with serum amyloid P protein, kappa and lambda light chains, and a 90-kd glycoprotein., Conclusion: The vascular involvement indicates that the blood vessel walls in the papillary dermis are the primary tissues affected during an acute photoreaction. The repeated acute damage and repair processes in the basement membrane zone result in thickening of the vessel walls. Perivascular deposits are a secondary and irreversible phenomenon resulting from the leakage and accumulation of different serum components. These changes were not found in the nonexposed skin, indicating that an increased level of erythrocyte protoporphyrin per se is not responsible for the cutaneous manifestations, but the interaction of solar radiation is mandatory. Amorphous deposits distinguish EPP from variegate porphyria and porphyria cutanea tarda; a histopathologic examination may be a helpful tool in differentiating porphyric and nonporphyric photosensitivity.

Autosomal recessive congenital ichthyosis (ARCI) is a rare, clinically and genetically heterogeneous genodermatosis. One gene (transglutaminase 1, on 14q11) and one additional locus (on 2q33-35, with an unidentified gene) have been shown to be associated with a lamellar, nonerythrodermic type of ARCI. We performed a genomewide scan, with 370 highly polymorphic microsatellite markers, on five affected individuals from one large Finnish family with nonerythrodermic, nonlamellar ARCI. The only evidence for linkage emerged from markers in a 6.0-cM region on chromosome 19p13.1-2. The maximum two-point LOD score of 7.33 was obtained with the locus D19S252, and multipoint likelihood calculations gave a maximum location score of 5.2. The affected individuals share two common core haplotypes, which makes compound heterozygosity possible. The novel disease locus is the third locus linked to ARCI, supporting previous evidence for genetic heterogeneity of ARCI. This is also the first locus for a nonlamellar, nonerythrodermic phenotype of ARCI.

Autosomal recessive congenital ichthyosis (ARCI) is a group of inherited disorders of cornification in which progress has recently been made in the identification of pathogenic mechanisms causing the disease. Transglutaminase 1 (TGM1) has been found as a defective gene in a large fraction of patients with lamellar ichthyosis (LI), a severe inherited scaling disorder of the skin. We have previously performed molecular genetic studies of 38Finnish ARCI families and found six different mutations in 13 families of 38 (34%). In this study we compared the molecular genetic alterations with clinical and electron microscopic findings of these patients. Families were classified by electron microscopy in ichthyosis congenita (IC) types I, II, III, IV and a non-defined group. TGM 1 gene mutation was found in all of the IC type II and 1/3 of the IC type 1 families. Although electron microscopy is not always used to classify ARCI patients, it can distinguish groups which are parallel with molecular genetic findings. This finding might be useful in the classification of ARCI patients for further linkage studies. Clinically typical phenotype of the TGM1 mutation carrier includes large, thick, brownish scales, but ichthyosis of some of these patients tends to be milder.

Autosomal recessive congenital ichthyosis (ARCI) is a rare, heterogenous keratinization disorder of the skin, classically divided into two clinical subtypes, lamellar ichthyosis (LI) and nonbullous congenital ichthyosiformis erythroderma (CIE). Recently, strong evidence for the involvement of the transglutaminase 1 gene (TGM1) in LI has evolved. We have studied ARCI in the isolated Finnish population, in which recessive disorders are often caused by single mutations enriched by a founder effect. Surprisingly, five different mutations of TGM1 (Arg141His, Arg142Cys, Gly217Ser, Val378Leu, and Arg395Leu) were found in Finnish ARCI patients. In addition to affected LI patients, we also identified TGM1 mutations in CIE patients. Moreover, haplotype analysis of the chromosomes carrying the most common mutation, a C-->T transition changing Arg142 to Cys, revealed that the same mutation has been introduced twice in the Finnish population. In addition to this Arg142Cys mutation, three other mutations, in Arg141 and Arg142, have been described elsewhere, in other populations. These findings suggest that this region of TGM1 is more susceptible to mutation. The corresponding amino acid sequence is conserved in other transglutaminases, but, for example, coagulation factor XIII (FXIII) mutations do not cluster in this region. Protein modeling of the Arg142Cys mutation suggested disruption or destabilization of the protein. In transfection studies, the closely related transglutaminase FXIII protein with the corresponding mutation was shown to be susceptible to degradation in COS cells, further supporting evidence of the destabilizing effect of the Arg142Cys mutation in TGM1.

We report on a 10-year-old Caucasian male with a prematurely aged appearance, delayed bone maturation and dental development, pronounced acro-osteolysis with brachydactyly, and distinctive cutaneous findings including hard, confluent skin lesions with some clinical and histologic resemblance to those of juvenile hyaline fibromatosis (JHF). He also had hyperopia, sensorineural hearing loss, and elevated TSH. Linear growth and intellectual functions were normal. We believe that this patient represents a new progeroid disorder.

Some alphaviruses, e.g. Sindbis, cause an acute febrile illness associated with papular rashes and arthralgia. The diagnosis is usually serological and, hence, the histopathology of the rashes has been poorly elucidated. We report on two patients with rapidly healing eruptions associated with Sindbis virus infection. The histopathology of the rashes showed large, pronounced lymphohistiocytic infiltrates with atypical lymphoid cells around the hair follicles, changes not usually seen in rapidly-healing dermatoses.

The epidermis serves an important protective function, which it manifests by producing an extensive cytoskeletal architecture, the unique feature of which are keratin filaments. Through studies that began with epidermolysis bullosa simplex (EBS) and now extend to a group of autosomal dominant human blistering skin disorders it was discovered that defects in the keratin genes lead to cell fragility and degeneration upon mechanical trauma. In most cases of EBS, point mutations occur in the keratin 5 (K5) and K14 genes expressed in the basal layer of the epidermis. The precise location of the mutation and the degree to which it causes perturbations in filament assembly correlate with disease severity. In the present study, we examine a case of EBS, which clinically lies at the severe end of the spectrum of Dowling-Meara EBS and which shows keratin filament clumping in suprabasal as well as basal cells. We show that one of the two K14 alleles has a single point substitution, giving rise to a Y129D mutation. This mutation resides 4 residues internal to the R125C/H hotspot known to account for the majority of Dowling-Meara cases. We provide functional and structural evidence to suggest why the Y129D mutation may be capable of creating such a severe form of EBS.

Malacoplakia, an inflammatory disease characterized by accumulations of phagocytic macrophages, occurs primarily in immunocompromised individuals. Cutaneous involvement is rare. Two men, each with a renal allograft, had expanding nodules on the temple and perianal area (case 1) and perianal, inguinal, and scrotal skin (case 2). Lesions resolved after combined surgical and antibiotic therapy. Histopathologic examination showed dense infiltration with large phagocytic macrophages containing round, concentric, laminar Von Kossa stain-positive inclusion bodies. Histiocytes had positive results for CD 68, lysozyme, and alpha 1-antitrypsin. Electron microscopic examination demonstrated rare intracytoplasmic inclusion bodies with concentric electron-dense laminations of calcium (Michaelis-Gutmann bodies.) Cutaneous malacoplakia should be considered in the differential diagnosis of nodules or draining ulcers, particularly in immunocompromised patients. Because Michaelis-Gutmann bodies are difficult to identify, specimens should be evaluated for cutaneous malacoplakia by immunohistochemical or electron microscopic means.

Migrating keratinocytes actively involved in reepithelialization in dermal wounds acquire a collagenolytic phenotype upon contact with the dermal matrix. To determine whether this phenotype is associated with repair in other forms of wounds, we assessed collagenase expression in 50 specimens representing a variety of blistering skin diseases, including subtypes of epidermolysis bullosa, porphyria cutanea tarda, bullous pemphigoid, pemphigus, transient acantholytic dermatosis, and suction blisters. Distinct from that seen in chronic ulcers or in normal healing by second intention, reepithelialization in these blistering conditions was not necessarily associated with a complete loss of basement membrane, as determined by immunostaining for type IV collagen. Collagenase mRNA was detected in the basal keratinocytes of several specimens of epidermolysis bullosa simplex (six of 10) and of pemphigus (three of seven), as well as in one quarter of transient acantholytic dermatosis samples in the presence of an intact basement membrane. In contrast, three of nine porphyria cutanea tarda, one third of epidermolysis bullosa acquisita, and one of 10 bullous pemphigoid samples had collagenase-positive basal keratinocytes with the basement membrane disrupted. The collagenase-positive lesions generally represented older blisters with evidence of epithelial regeneration. Collagenase was also expressed in suction blisters at 2 and 5 d after induction of the blister, but was shut off when the epidermis had healed. Other metalloproteinases were expressed occasionally, if at all. Our results suggest that keratinocyte migration is associated with collagenase expression and that contact of keratinocytes with the dermal matrix is not necessarily needed for collagenase induction.

Functional disturbance of p53 tumor suppressor protein contributes to uncontrolled cell growth. Human papillomavirus (HPV) E6 oncoproteins bind to wild-type p53 and abrogate its function. Our objective was to elucidate the relation of aberrant p53 protein expression to HPV DNA and cellular atypia in male genital warts and premalignant lesions. Immunohistochemically detectable p53 protein expression was studied in 35 male anogenital warts with low-level or no keratinocyte atypia (histologically confirmed condylomata acuminata), in 25 lesions with bowenoid papulosis (BP; carcinoma in situ) histology, and in 10 non-condyloma lesions using immunostaining with three established antibodies recognizing full-length wild-type accumulated p53 protein, or its conformational mutants. HPV DNA specific for HPV 6/11, 16/18, or 31/33/35 was identified by in situ hybridization or by polymerase chain reaction (PCR) - based amplification. Both nuclear and cytoplasmic keratinocyte immunostaining for p53 protein was detected in 41% of condylomata with no keratinocyte atypia and in 42% of condylomata with slight nuclear atypia or with bowenoid papulosis histology. No association of aberrant p53 expression with any specific HPV type or with HPV DNA was observed. Normal skin and some other penile dermatoses were negative for p53 immunostaining. In the follow-up biopsies of 16 BP patients, treated with CO2 laser, recurrence of atypia was seen exclusively in lesions initially positive for both HPV DNA and p53 protein. Our results show that a few cells in male genital warts even with no cellular atypia may express abnormally sequestered or loss-of-function p53 protein, and that concomitant presence of any type of HPV DNA is associated with recurrencies or progression of premalignant changes.

Background: Macular atrophy or anetoderma is a rare skin disease of unknown pathogenesis, characterised by wrinkled or flaccid skin., Objective: The finding of anetoderma in 5 patients followed up because of false-positive seroreactions of syphilis prompted us to study the occurrence of antiphospholipid (aPL) antibodies in anetoderma., Methods: 14 unselected patients with primary anetoderma (PA) were collected from hospital records and clinical, immunological and histological findings were compared in the two patient groups., Results: Of the 5 patients, 3 fulfilled the criteria for antiphospholipid syndrome. In two cases, it was secondary to systemic lupus erythematosus (SLE). Of the 14 PA patients 1 had aPL antibodies and 4 had borrelia antibodies. Two patients had thyroid antibodies; 1 of them developed SLE. In several biopsy specimens, microthromboses were seen in both patient groups., Conclusion: On the basis of this study and our previous findings, it seems that anetoderma is more often associated with aPL-positive SLE or lupus-like disease than with aPL-negative disease. Immunological mechanisms play an important role in both primary and secondary anetoderma. The meaning of false-positive serological tests for syphilis or borrelia and aPL antibodies is not clear, but they may be reacting to some still unidentified antigen. Probably, various systemic as well as local inflammatory and non-inflammatory processes, e.g. microthromboses, can trigger anetoderma via still unknown pathomechanisms.

Background and Objectives: We have evaluated the efficacy of CO2-laser in eradicating human papillomavirus (HPV) DNA from genitoanal skin lesions., Study Design: Biopsies of 38 male patients with histologically confirmed HPV-infection after an average of 2 years of follow-up were analyzed. Post-treatment biopsies were obtained from all residual or recurrent HPV-suspect (acetowhite) lesions in 23 patients., Results: After an average of three separate CO2-laser treatments, 15 of 38 patients were devoid of any clinical or acetowhite lesions. By in situ hybridization (ISH), the frequency of HPV-types 6/11 decreased from 52% to 26%, and HPV-types 16/18 decreased from 48% to 17%, respectively, in 23 patients biopsied twice. When ISH-negative biopsies were further analyzed with polymerase chain reaction (PCR) and southern blotting (SB) for HPV-16, HPV-types 16/18 were detected in a total of 65% of biopsies before CO2-laser therapy, and in 61% after the therapy. The cure rate achieved with CO2-laser was 39% (15/38) according to clinical, 61% (14/23) according to histopathological, and 26% (6/23) according to molecular biological criteria. The frequency of Bowenoid papulosis was reduced from 57% (13/23) to 17% (4/23)., Conclusions: Although CO2-laser is ineffective in eradicating HPV genome from therapy-resistant penile warts, the treatment reduces the recurrence of atypical changes and visible warts.

Based on electron microscopic features, recessive congenital ichthyoses have recently been divided into four subgroups designated ichthyosis congenita (IC) types I, II, III and IV. Type II is characterized by cholesterol clefts in the horny cells, type III by perinuclear elongated membranes in the granular and horny cells, and type IV by masses of lipid membranes in granular and horny cells. Clear electron microscopic criteria for type I are lacking, although the presence of lipid droplets in the horny cells has been suggested as a criterion. In the present study we included ichthyosis patients with (i) recessive inheritance, (ii) erythrodermic fine scaling, (iii) lack of fine structural markers of IC types II-IV. Patients with ichthyotic syndromes were excluded. The case material consisted of 21 patients from 14 families. Eight were collodion babies at birth, but three were normal. Nine had ectropion, the flexures were affected in 12, and the palms and soles were thickened in all but one patient. On electron microscopy lipid vacuoles in the horny cells were common, but were absent in four patients. Changes in other lipid-related structures, including keratinosomes, were common. We conclude that currently type I can be diagnosed only by excluding the other types of ichthyosis. Clinically, IC type I corresponds to classical non-bullous congenital ichthyosiform erythroderma, but there is marked heterogeneity among affected individuals.

Two patients suffering from ichthyosis with unusual ultrastructural features were examined. One was a 14-year-old boy with ichthyotic skin since birth. The ichthyosis was initially erythrodermic and later presented as follicular hyperkeratosis. The other patient was an ichthyotic child who died 2 days after birth of respiratory distress syndrome. Although apparently not consanguineous, both families came from the same relatively isolated rural area and autosomal recessive inheritance seems likely. Light microscopy did not yield diagnostic features, but the ultrastructural findings in the granular and horny cells showed diagnostic lamellar membrane packages. Identical ultrastructural features have previously been published in one prematurely born baby who died soon after birth and once in a prenatal diagnosis in the same family; the disease was termed "ichthyosis congenita type IV".

Background: The homogeneous material found in the skin is commonly identified as amyloid. We describe a previously unknown disease that is caused by proteinaceous deposits and that does not fulfill the criteria of the earlier recognized amyloid diseases., Observations: The unusual deposits, which were initially found in the dermis, were ultrastructurally composed of fibrillar material with a tubular substructure. Immunohistologically, the material was tested using a large panel of antibodies, and the results revealed that it was unlike any commonly known proteinaceous material. The deposits later spread to other organs and disturbed the vital functions of the body., Conclusions: We describe a unique syndrome characterized by fibrillar extracellular deposits that was recognized and differentiated from other similar clinical syndromes by ultrastructural examination. Further biochemical analysis is necessary to identify the origin of the material.

We have examined a family with 4 members in three succeeding generations suffering from a severe keratinization disorder. The clinical phenotype, with symmetric plaques on the extremities, corresponded to erythrokeratodermia progressiva symmetrica. It was manifested at birth, however, and in addition to the hyperkeratotic plaques, follicular hyperkeratosis was also observed. Electron microscopy revealed multiple morphological changes such as myelinated membrane structures, or needles, which were similar to those occurring in ichthyotic disorders and tyrosinemia, as well as in harlequin fetuses, all of which were excluded clinically or biochemically in our patients.

The fine structure of Langerhans cells (LC) in four rare types of ichthyosis, namely recessive ichthyosis congenita type II, III and IV and ichthyosis hystrix Curth-Macklin was examined. Signs of LC activation were observed in eight of 21 patients. In IC type IV, the rare occurrence of a mitotic LC was observed. It is possible that LCs are secondarily activated in keratinization disorders.

We report on 3 patients with the cardio-facio-cutaneous (CFC) syndrome. Each of them was a sporadic case in the family. The severity of the psychomotor retardation varied from mild to severe. Skin manifestations were often minimal, but each patient had abnormally curly and brittle hair. A skin biopsy from one of the patients showed vellus hair cysts filled with keratin, and the hair follicles were surrounded by unusually thick fibrotic sheaths.

The extent to which the clinical diagnosis of male condylomata acuminata (CA) will be improved by histopathologic examination, immunohistochemical demonstration of papillomavirus common antigen (BPV), or demonstration of human papillomavirus (HPV)-specific DNA was studied. The relation of nuclear atypia to local cytodestructive therapy and specific HPV types was also analyzed. Altogether, the diagnosis could be histologically verified in 116 of 133 (87%) patients with clinically suspected penile CA. Of these, 69 (59%) had a positive result in in situ DNA hybridization for one or more of HPV types 6/11, 16/18, 31/33/35, or 31/35/51. Atypical cells were observed in 53 CA biopsies (46%), and there was a statistically significant correlation between this finding and the high risk HPV types 16/18, 31/33/35, and 31/35/51. Seventeen patients had neither histologic signs of condyloma acuminatum, nor detectable BPV antigen, and in situ hybridization showed HPV type 31/33/35 DNA in one biopsy, and HPV type 6/11 DNA in another. No correlation between the atypical changes and the type of previous therapy for the warts was found. Our results indicate that histopathologic examination supplemented with new HPV-specific methods is an important tool in diagnosing HPV infections.

We have compared the efficacy of digoxigenin- and biotin-labelled probes in detecting HPV DNA by in situ hybridization on paraffin-embedded tissue sections of 57 male condyloma-suspect genital lesions. Each biopsy was hybridized with at least three of the following four methods: digoxigenin-labelled HPV DNA probes (Dig-HPV), biotinylated HPV-DNA probes (Bio-HPV), and two commercial methods (ViraType in situ and PathoGene), both based on biotinylated DNA probes. The hybridization products were visualized with colourigenic enzyme substrates. In most biopsies, the 4 methods gave equal results although cross-hybridization was most often found with the low-stringency ViraType method. Dig-HPV 6/11 probes gave positive results about twice as often as either of the commercial methods. No such difference, however, was found for HPV 16/18 probes. DNA of any type of HPV 6/11, 16/18 or 31/33/35 or 51 was detected in 28/43 (65%) of lesions showing condyloma acuminatum histology but in none of the 14 biopsies with no histological signs of HPV infection. In HPV-positive condylomata with no cellular atypia. HPV 6/11 was detected in 87% (13/15), and HPV 16/18 in 27% (4/15). In biopsies with cellular atypia, HPV types 6/11 were detected in 62% (8/13), HPV types 16/18 in 46% (6/13), and HPV types 31/33/35 or 51 in 50% (6/12). In about 50% of the biopsies where at least one hybridization method gave a positive result, either one of the commercial methods gave a negative result.(ABSTRACT TRUNCATED AT 250 WORDS)

The recessively inherited congenital ichthyoses have ultrastructural features which indicate abnormal epidermal lipid metabolism. The ultrastructural markers of the three recessive congenital ichthyosis groups are lipid droplets in horny layers (type I), cholesterol clefts (type II) and membrane structures (type III). We describe six patients from five families belonging to the last group. The variable clinical phenotype alone does not allow the delineation of this disease, but together with the ultrastructural characteristics the subtype is unequivocal. In addition to the membrane structures, half of the cases showed abnormal keratinosomes and vesicular complexes. Membrane-bound vacuoles and needle-like slits were exceptionally found. The onset of the ichthyosis was variable, in contrast to other patients described under the heading recessive congenital ichthyosis.

Five patients with porphyria cutanea tarda (PCT) were treated with a prolonged, low-dose chloroquine regimen (250 mg twice weekly). Their skin symptoms disappeared, and the abnormal urinary porphyrin excretion normalized during treatment periods ranging from 6 to 17 (mean 11.8) months. The morphology of the skin was studied by light and electron microscopy methods before treatment, at the onset of remission, and 6-12 months later. In samples taken during remission, the PAS-positive thickening of the superficial dermal vessels was comparable to that before treatment. In electron microscopy, the vessels showed thickening because of reduplication of the basal lamina and perivascular deposition of amorphous material; no consistent changes were found during remission. The results show that the histopathological changes of the skin in PCT are of chronic nature, and are probably irreversible.

Skin manifestations were described in lupus anticoagulant (LA) positive and in LA negative SLE patients. Necrotic ulcers appearing at the beginning of the disease process characterized the 33 LA positive patients. Thirteen patients had a "peripheral vascular syndrome"; small leg ulcers of livedoid vasculitis type following deep venous thromboses, in 3 patients developing into pyoderma gangrenosum like ulcers and in 2 patients into pseudo-sarcoma Kaposi. The lesions were histologically characterized by capillary angiogenesis with extravasated red blood cells, sparse inflammatory cell infiltrates and microthromboses. Three patients had ulcers clinically and histologically resembling those seen in Degos' disease. Five patients had anetoderma showing elastic tissue depletion and microthromboses histologically. A different pattern of skin changes was seen in the LA negative patients. Our findings suggest that antiphospholipid antibodies play a pathogenetic role in the described skin manifestations of LA positive SLE patients.

In the heterogeneous group of recessive congenital ichthyoses the disorder of desquamation seems to be a basic problem. Desquamation is strongly dependent on the normal lipid metabolism of the keratinocytes. We describe a group of patients who have a typical clinical picture of large scale ichthyosis and cholesterol clefts in the thickened corneal layer, evidencing a disturbance of the lipid metabolism of the skin. The corneocytes also show a thin or absent cornified envelope, which could indicate a disturbance of protein synthesis. These patients have a severe ichthyosis, but good general health and no associated symptoms. This disorder has recently been named 'ichthyosis congenita type II' by the Heidelberg group on the basis of electron microscopic findings. According to the present examination this group corresponds clinically to the currently used diagnosis 'lamellar ichthyosis'.

A patient with dystrophic epidermolysis bullosa inversa was studied using electron microscopy and indirect immunofluorescence using antibodies to matrix macromolecules of the dermoepidermal junction zone. There was splitting below the lamina densa with an apparently normal basement membrane, but a lack of intact anchoring fibrils and with a disarranged papillary connective tissue. Indirect immunofluorescence examination with antibodies to type VII collagen, the major structural protein of anchoring fibrils, showed a normal linear staining pattern. Synthesis of type VII collagen which is unable to form stable, resistant anchoring fibrils may be a distinct feature of this subtype of recessive dystrophic epidermolysis bullosa.

The skin of 20 patients with variegate porphyria (VP) was studied using light, fluorescent, and electron microscopy. Twelve patients had skin symptoms and markedly increased fecal protoporphyrin excretion. Their sun-exposed skin was characterized by homogeneous PAS-positive thickening and IgG deposition in the vessel walls. The basic ultrastructural change was thickening of the vascular walls caused by reduplication of the basal lamina and perivascular deposition of amorphous material. Qualitatively similar but less prominent histopathological changes occurred in sun-protected skin in some of the patients. Six patients had no skin symptoms but an increased porphyrin excretion. The light microscopical changes were comparable to those in the patients with skin symptoms, but the ultrastructural changes were less severe. No abnormal histopathological changes occurred in two symptomless patients who had low lymphocyte protoporphyrinogen oxidase activity but normal fecal porphyrin excretion. These results show that the primary site of skin damage in VP is the vessel wall, and that histopathological changes of the skin also occur in porphyric patients who have never had skin symptoms. Factors determining the occurrence of skin symptoms in VP are discussed.

The pathogenesis of a rare form of the ichthyotic diseases, ichthyosis hystrix Curth-Macklin, was investigated by immunohistochemistry and electron microscopy. Monoclonal antibodies (Mabs) against keratins expressed in normal basal cells (PKK2 and KA1), Mabs against keratins only present in normal fetal skin (PKK1), and Mabs against keratins 1, 2, 10, and 11 (KA5 and K8.60) were used. The Mabs reacting with normal basel cells showed an increased reaction with many cell layers. The Mab PKK1 distinctly reacted with the basal cell layer, suggesting an expression of fetal keratins. Electron microscopic study of both normal-looking and involved skin revealed the keratinization disorder characterized by tonofilament shells, perinuclear vacuoles, and binuclear keratinocytes. The results suggest that there is no prematurity of keratinization, but rather a pathological expression of specific keratin genes leading to expression of fetal keratins in this form of ichthyosis hystrix.

We have studied the relationship of antibodies reacting with human retroviral core proteins to the disease outcome in Finnish mycosis fungoides (MF) patients in a prospective manner. Antibodies recognizing human T-cell leukaemia/lymphoma virus I (HTLV-I) or human immunodeficiency virus type 1 (HIV-1) core proteins were found in 12 of 14 MF patients as shown by the Western blot method. The antibody reactivities showed three patterns: three patients had antibodies cross-reacting with the gag-encoded core proteins of both HTLV-I and HIV-1; seven patients showed antibodies reacting with HTLV-I core proteins only; and the sera of two patients reacted with HIV p24 core protein only. When following the clinical course of these patients, we found that the three patients with antibodies cross-reacting with both viruses had the most fulminant clinical course, and the overall duration of MF was, on average, 4 years less than in the rest of the patients. None of the patients, however, became leukaemic, or showed any other features suggestive of acute T-cell leukaemia/lymphoma (ATL). Two patients, who did not show anti-retroviral antibodies during the follow-up, had a stable disease with plaque-type skin lesions. Histological or immunohistological typing of the skin infiltrates did not correlate with the disease outcome or the above antibody patterns. Our results thus raise the possibility that an unknown retrovirus, immunologically related to the known human retroviruses, may be aetiologically linked to MF.

88 cases of microscopical diapedesis of the red blood cells in the superficial blood vessels of the skin were investigated clinically, histologically and immunohistologically. Polymorphonuclear vasculitis (PMNV) was found in 27 cases, 18 of which also demonstrated immunoglobulins (mostly IgM) in the vessel walls. Complement (C3) was found in 16 cases. The cases with PMNV formed a uniform group as regards preceding infections, drug consumption, clinical features, and pathological urinalysis and laboratory data. The second group consisted of 21 cases of lymphocytic perivasculitis with immunoglobulins and/or complement (LP + ig/C3). It clearly differed clinically from the former group in three respects: urinalysis was normal, a slowing of the venous outflow was found in more than half of the cases and the duration of the disease was longer. The biggest group consisted of 40 cases of lymphocytic perivasculitis without detectable immunoglobulins in the vessel walls (LP). In this group the duration of the disease was shortest. The capillary resistance was lower than in the other groups. The results of this investigation indicate that there are at least three pathogenetically differing groups among the clinical purpuric conditions.

The light and electron microscopic structure of pityriasis rubra pilaris (PRP) is described in five patients. Hyperkeratosis, hypergranulosis, keratotic plugs in the follicular openings, acanthosis and focal parakeratosis were observed. A moderate perivascular infiltrate was seen in the upper dermis. Electron microscopy revealed moderately activated keratinocytes, a decreased number of tonofilaments and desmosomes, enlarged intercellular spaces, parakeratosis with lipid-like vacuoles and a large number of keratinosomes. Lymphoid cells were present in the epidermis in moderate numbers. At the dermo-epidermal junction, the basal lamina was focally split, containing gaps. Etretinate therapy produced moderate to marked clinical improvement. The histological picture improved but the typical signs of PRP, including follicular plugging, persisted. Ultrastructurally the cellular activity and the amount of hyperkeratosis and parakeratosis decreased, while increases in keratinosomes, intercellular substance, microvilli and desmosomes were observed during treatment.

An electron microscopic study was performed to demonstrate the pathological changes induced by long term PUVA treatment in recalcitrant psoriasis. Three patients developed mottling (hyperpigmentation and hypopigmentation) during two to three years of treatment. Three different types of morphological changes were found: disarrangement of keratinocytes, clustering and stimulation of melanocytes and homogenization of papillary dermis. Furthermore, the superficial blood vessels were loaded with the same type of amorphous granular substance. These changes might be specific to PUVA treatment or they might occur only in patients with previous treatment with, e.g., arsenic, methotrexate, anthralin + UVB or a combination of these.

A 27-year-old man had had Fanconi's anemia (FA) for 20 years. The patient had pancytopenia, retarded growth, hypogonadism, and chromosomal aberrations. He had freckle-like and darker pigmented macules scattered on his chest, shoulders, upper part of the back, and hips, with interspersed, hypopigmented areas. Biopsy specimens taken from both the hyperpigmented and hypopigmented spots showed a derangement of keratinocytes and nuclear abnormalities, more notable on sun-exposed skin sites. The patient also had numerous tumor-like, recalcitrant, viral warts. Immunologic studies showed normal humoral immunity, but there was evidence of depressed cell-mediated immunity. We speculate that the chromosomal aberrations, the depressed cell-mediated immunity, and the increased frequency of malignant neoplasms known to occur in patients with FA also reflect changes related to an increased susceptibility to viral infections.

A 36-year-old healthy man with atypical necrobiosis lipoidica of the face is described. The lesions were annular with a raised erythematous palpable border. The centres were slightly depigmented and atrophic, without telangiectasia or hair loss. Histopathological changes revealed prominent giant cells in small groups without clear granuloma formation. They were located at all levels of the drmis between the collagen bundles.

The uninvolved skin of patients with psoriasis was examined microscopically. Atypical nuclear features in keratinocytes and melanocytes were found in about half of the patients. The patients treated with psoralens and UV-A (PUVA) had significantly more of these changes than did patients without PUVA treatment, and the risk was dose dependent. Previous arsenic treatment and x-ray irradiation seemed to have a similar effect. The changes may have been due to the shortwave UV range of the light source.

Dark red nodules that drained an opaque amber liquid developed on the extensor surfaces of both legs in a 69-year-old woman receiving furosemide and spironolactone for congestive heart failure. In addition to asymptomatic cholelithiasis, the serum amylase, lipase, and uric acid levels were elevated. Other skin signs and joint manifestations of gout were absent. A biopsy revealed a granuloma with the needle-like crystals characteristic of gout.