Search

Background: An 8-year-old girl presented with hundreds of milia, measuring 1 to 2 mm; comedone-like lesions; skin-colored and hyperpigmented papules on the face, scalp, ears, neck, upper trunk, and lower arms along with diffuse scalp hypotrichosis; and pinpoint palm/sole pits. Onset was in early childhood and the disease was historically present in 6 generations., Objective: Our objectives were to delineate the clinical and histopathologic features and mode of inheritance as a base for gene studies., Methods: Eighteen family subjects were studied. Twenty-six skin biopsy specimens were examined. A detailed pedigree was constructed. A complete literature search was done concerning diseases with generalized basaloid follicular hamartomas., Results: The lesions were basaloid follicular hamartomas and other folliculocentric abnormalities. Inheritance was autosomal dominant. Extensive literature search confirmed the finding of a unique genodermatosis., Conclusion: A new genodermatosis termed dominantly inherited generalized basaloid follicular hamartoma syndrome was defined by delineating its clinical and histopathologic features and mode of inheritance and by extensive literature review.

In this study, an in vitro model of immune complex-mediated basement membrane zone separation caused by periphigoid antibodies, serum complement, and peripheral blood leukocytes is described. When cryostat sections of fresh-frozen normal human skin were treated with either of 4 bullous pemiphigoid sera containing complement-activating anti-basement membrane zone antibodies and subsequently incubated at 37 degrees C with normal human peripheral blood leukocytes and fresh human serum, leukocytes attached to 96% of the basement membrane zone in 100% of sections. Sixty-seven percent of the sections developed focal areas of basement membrane zone separation resembling dermal-epidermal separation described in early pemphigoid lesions. In control sections in which either leukocytes, pemphigoid antibody or fresh human serum were omitted, significantly less leukocyte attachment and basement membrane zone separation occurred. Evidence that leukocytes caused separation was supported by an absolute requirement for viable leukocytes during incubation, a high correlation between leukocyte attachment and separation and experiments showing that leukocytes attached to the basement membrane zone were activated. This study provides the first in vitro evidence directly supporting a functional role for immune-complex mediated inflammation in the pathogenesis of basement membrane zone separation and blisters in bullous pemphigoid.

Epidermolysis bullosa acquisita (EBA) is an immunologically distinctive disease with characteristic clinical features. These include extreme skin fragility, trauma-induced blisters and erosions, and healing with scars and milia. These clinical features are currently the major means of routinely distinguishing EBA from bullous pemphigoid (BP) and cicatricial pemphigoid (CP). In this study we describe five patients with EBA who presented with or developed clinical as well as histologic and immunohistologic features indistinguishable from those characteristic of BP or CP. At different times during the course of their disease, it closely resembled classic BP or CP and cases of BP or CP with atypical features or evolving features of EBA. To determine how often EBA might present and be misdiagnosed as BP, we reviewed our experience with bullous diseases and screened eighty-five "BP" sera for EBA antibodies. The results of this study show EBA can mimic the clinical, histologic, and immunohistologic features of BP and CP, suggest that a BP-like clinical presentation occurs in as many as 50% of EBA patients, and suggest that 10% of patients referred to medical centers and diagnosed as BP have EBA.

Direct immunofluorescence microscopy has shown that a linear pattern of immunoglobulin and/or complement deposition at the cutaneous basement membrane zone is a characteristic feature in a number of acquired bullous diseases and is occasionally observed in systemic lupus erythematosus. Immunoelectron microscopy has shown the linear pattern of immunofluorescence may be produced by immune deposits located either above the basal lamina (in the lamina lucida) or below the basal lamina (in the upper dermis). Distinguishing between these sites of immune reactant deposition may be of value in differential diagnosis. In this study we report a double immunofluorescent method by which skin biopsies with linear IgG immunofluorescence due to deposits above the basal lamina (bullous pemphigoid) could be distinguished from biopsies with deposits beneath the basal lamina (bullous systemic lupus erythematosus and epidermolysis bullosa acquisita). When skin sections were treated sequentially with rhodamine-labeled anti-human IgG followed by fluorescein-labeled antilamina lucida (pemphigoid) antibody and examined by fluorescence microscopy, the following results were obtained. In biopsies with IgG deposits in the lamina lucida, a single green fluorescent band was observed. In tissues with subbasal lamina deposits, either parallel and contiguous bands of green and yellow-orange fluorescence or a single band of yellow-orange fluorescence was observed. The method is simpler, quicker, and less expensive than immunoelectron microscopy and should be a useful technique for evaluating skin diseases with linear immunofluorescence at the basement membrane zone.

A patient had papular and nodular cutaneous deposits of mucin and cutaneous and systemic manifestations of lupus erythematosus (LE). Since many of the mucinous deposits occurred at sites that were clinically free of skin lesions of LE, we considered initially that the patient had both LE and papular mucinosis. However, after a review of the English literature and further study of the patient, it seemed more likely that the papular and nodular deposits of mucin were secondary to LE and not a previously unreported simultaneous occurrence of the two diseases in the same patient. To our knowledge, this is the third case report of a patient with papular and nodular cutaneous mucinosis secondary to LE. In addition to the case report, this article is concerned with a discussion of cutaneous mucinosis in LE and other "collagen vascular" diseases.

There is an expanding list of syndromes that combine ichthyosis with neuroectodermal and mesodermal defects. We present the case of a young woman with the following features: lamellar ichthyosis, dwarfism, mental retardation, nail and dental abnormalities, unusual facies, poor sexual maturation, punctate cataracts, and hair shaft abnormalities. There were no neurologic or auditory defects. Hair examination revealed pili torti, trichoschisis, bright and dark bands with polarizing microscopy, and a low hair sulfur content. The patient did not have aminoaciduria or immunoglobulin abnormalities. We believe that this case is a link between the ichthyosis-associated syndromes and the group of syndromes that have in common abnormal hair with clean transverse fractures (trichoschisis) and low sulfur content. A more complete examination of the hair in other patients with ichthyosis and associated abnormalities will probably reveal more patients with this new syndrome.

A superficial shave biopsy is described as a simple, essentially painless, more reliable method for the demonstration of the scabies mite, eggs, and feces in human skin.

It has been proposed that cutaneous inflammation and blister formation in bullous pemphigoid is caused by antibodies to the cutaneous basement membrane zone which active complement, thereby, attracting leukocytes to the dermal-epidermal junction. There is, however, no functional evidence which supports a role for pemphigoid antibodies in complement activation or leukocyte activity in skin. This study describes the in vitro attachment of human peripheral blood leukocytes to the dermal-epidermal junction of cryostat skin sections treated with 9/13 pemphigoid sera containing antibodies to the cutaneous basement membrane zone. A requirement for complement in the reaction was supported by the findings that only complement-fixing pemphigoid sera mediated the leukocyte response, a strong correlation existed between complement-fixation titers and leukocyte attachment titers and only leukocytes suspended in fresh serum but not buffer or heat inactivated serum attached at the junction. A requirement for antibody was supported by the observation that IgG fractions of 4 pemphigoid sera were as effective as whole sera in mediating leukocyte attachment. The leukocyte response was shown to be specific for complement-fixing pemphigoid sera since it was not observed with noncomplement-fixing sera or sera from 15 normal human and 22 nonpemphigoid disease controls. This study offers functional evidence for an interaction between pemphigoid antibody, complement and leukocytes in the immunopathogenesis of bullous pemphigoid and demonstrates that complement-fixing antibasement membrane zone antibodies may be important in initiating the cellular inflammatory events observed near the dermal-epidermal junction in vivo.

A patient had sensory radicular neuropathy. The patient demonstrated features characteristic of this entity: (1) recurrent trophic ulcerations of the hands and feet, (2) onset in early adulthood, (3) distal, dissociated loss of pain and temperature sensation far out of proportion to the loss of other sensory perceptions, and (4) complete sparing of motor function.

Generalized hyperpigmentation developed over 2 years in a 65-year-old woman. A diagnosis of pernicious anemia was made, and treatment with vitamin B12 led to complete reversion of her hyperpigmentation to normal. Literature pertinent to hyperpigmentation and its association with megaloblastic anemias is reviewed and several possible mechanisms are mentioned.

Previous immunofluorescent studies showing deposits of immunoglobulin and complement at the cutaneous basement membrane zone have provided evidence supporting a role for immune complexes in the pathogenesis of bullous pemphigoid. In this study the functional activity of the deposits has been examined using leukocyte attachment, a method for detecting and quantitating the biological activity of complement-activating immune complexes in tissues. When peripheral blood leukocytes suspended in serum complement were incubated with cryostat sections of lesional and adjacent normal-appearing skin from 9 patients with pemphigoid, skin from 11 normal controls and lesional skin from 14 nonpemphigoid disease controls there was significantly greater attachment of leukocytes to the basement membrane zone of lesional bullous pemphigoid skin compared to normal-appearing pemphigoid skin and skin of both control groups. A significant reduction in attachment in the absence of serum complement suggested the reaction was dependent on activation of complement by tissue-deposited complexes. Although leukocyte attachment was greater in lesional than normal-appearing pemphigoid skin, a comparison of the incidence and intensity of cutaneous IgG and complement immunofluorescence between the 2 groups showed no significant differences. Furthermore, no correlation between leukocyte attachment and serum titers of immunoglobulin G or complement-binding anti-basement membrane zone antibodies was observed. These results suggest that immune reactants in lesional pemphigoid skin are functional complement-activating immune complexes, that differences exist between the activity of complexes in lesional and normal-appearing pemphigoid skin and may explain why lesions develop at some sites and not others.

Definitions are offered for quality of health care, reasonable costs or fees, an appropriate share of the dermatologic market, and reasonable income or profit for dermatologists. Physician control of these items was almost complete in the recent past, but control is now passing rapidly to government in the form of regulations and to large health care corporations in the form of unbridled competition in the marketplace. Physicians, including dermatologists, must mobilize and unite to retain reasonable controls, especially over quality care and personal income. The Academy (as an organization of all of us) can help in this process, but individual dermatologists at local, regional, and national levels must play major roles in retention of controls.

The purpose of this study was to define the ultrastructural defects and pathogenesis of epidermolysis bullosa dystrophica-recessive (EBD-R). The only consistent ultrastructural alteration found in EBD-R was an absence of anchoring fibrils. In many specimens of nonblistered, nontraumatized EBD-R skin, absence of anchoring fibrils was the only ultrastructural abnormality observed. The possibility that lack of anchoring fibrils was a secondary change resulting from previous blistering and scarring was eliminated by our observation that anchoring fibrils were consistently absent in the never previously blistered skin of two newborns with EBD-R. In experimentally traumatized skin, the epidermis and dermis separated in the region of the epidermal-dermal junction normally occupied by anchoring fibrils. Basal lamina and dermal microfibril bundles appeared to be normal. Using recombinant grafts, we demonstrated that anchoring fibrils were not formed by EBD-R dermis when combined with EBD-R epidermis or normal epidermis. Anchoring fibrils were formed when normal dermis was combined with normal and EBD-R epidermis. These studies indicate that the defect in EBD-R resides in the dermis and that the defect may be associated with impaired formation of anchoring fibrils.

Bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA) are chronic blistering diseases associated with circulating complement (C)-binding anti-basement membrane zone (BMZ) antibodies and tissue-deposited immune complexes at the BMZ. Experimental evidence supporting a role for C-activating immune complexes in the pathogenesis of dermal inflammation and blisters has been reported in BP but not in EBA. In this study tissue-deposited immune complexes composed of EBA or BP antibodies were tested for generation of C-dependent chemotactic activity and the capacity to cause dermal leukocyte infiltration and dermal-epidermal separation (DES). Chemotactic activity was measured by the leukocyte attachment (LA) method. The capacity of complexes to mediate leukocyte infiltration and DES was examined in vitro using a newly described organ culture method. The results of LA showed immune complexes formed in vivo in EBA skin or in vitro by treating normal human skin with EBA antibodies were significantly more active in mediating C-dependent chemotaxis than complexes in BP skin or those formed with BP antibodies of equivalent or higher C-binding titers. Furthermore EBA antibodies and C caused leukocyte infiltration and DES in organ culture while BP antibodies did not. These results support a role for C-binding anti-BMZ antibodies in the pathogenesis of EBA lesions and demonstrate differences in the capacity of BP and EBA immune complexes to generate C-dependent chemotactic activity. These results suggest factors in addition to C-binding titers are important in the activation of C by BP and EBA immune complexes and suggest chemotactic factors other than those derived from C activation may be important in the recruitment of leukocytes in BP.

Five patients with disseminated cryptococcosis had lesions on the extremities resembling cellulitis, which evolved into areas of blistering and ulceration in three patients. All had underlying disease and were medically immunosuppressed. Disseminated cryptococcosis appears to present with cellulitis or herpes-like vesiculation more commonly than is currently appreciated. India ink preparations of aspirates from areas of cellulitis or Tzanck preparations from blisters may show characteristic organisms, and make possible an immediate diagnosis of cutaneous cryptococcosis. If cutaneous infection is confirmed by performing biopsies and growing cultures, dissemination must be presumed and the patient treated with a full course of systemic antifungal therapy. With increasing awareness of cutaneous involvement, some cases of disseminated cryptococcosis will be diagnosed sooner, leading to earlier therapy and improved prognosis.

Most of the world's population is eventually infected with herpes simplex virus type 1, type 2, or both. Most infected persons harbor latent virus in nerve ganglia for the rest of their lives. True primary infections, nonprimary first-episode infections, and recurrent infections can be asymptomatic or clinical, but all of these are contagious. Past estimates of recurrent herpes affecting 20% to 40% of the population are probably low because of inadequate studies of asymptomatic shedding and genital recurrences. Herpes infections are spread primarily by close personal contact but some are contracted by fomites and medical-dental procedures. Latent virus harbored by almost everyone with frequent reactivation to produce symptomatic or asymptomatic, infectious recurrent disease poses a huge problem for control or eradication of herpes simplex infections. Public health measures will probably fail because they require too much alteration of the public's life-styles. So far, antiviral drugs do not eliminate latent virus from infected ganglia. That naturally infected persons can be reinfected, superinfected, or autoinoculated raises serious questions whether vaccines will eradicate the disease, although they might control some serious manifestations and limit some spreading. The problem of eradicating herpes is different from that of eradicating smallpox, where latent infections with infectious recurrences did not exist.

Whole-skin grafts from a patient with lamellar ichthyosis were maintained on athymic nude mice for periods of 6 weeks to 4 months with excellent preservation of all gross and histologic features of the disease. In recombinant grafts composed of lamellar ichthyosis epidermis and normal dermis grown for periods up to 87 days on nude mice, the abnormal epidermis retained all the features of lamellar ichthyosis. Similar results were found in recombinants of lamellar ichthyosis epidermis and dermis. In recombinant grafts of normal epidermis and lamellar ichthyosis dermis, the epidermis remained normal and did not become ichthyotic. These observations support the hypothesis that the defective gene in lamellar ichthyosis acts directly on the epidermis as opposed to acting indirectly through a systemic abnormality or through an effect on neighboring dermis.

A woman with cutaneous vasculitis had a severe bullous eruption that was suggestive of erythema multiforme. The patient also had a history of recurrent urticaria that continued intermittently for over a year of follow-up examination. Skin biopsy specimens of both urticarial and erythema and multiforme lesions showed leukocytoclastic vasculitis. An illness resembling systemic lupus erythematosus (SLE) is suggested by transient, low-titer, positive antinuclear antibody tests, persistent deposits of immunoglobulin and complement in normal skin, arthralgias, circulating immune complexes, and chronic hypocomplementemia. This case is similar to cases previously reported as "hypocomplementemic vasculitis," an "unusual SLE-related syndrome," and "urticaria with vasculitis."

Ultrastructurally, the epidermal-dermal junction is composed of four component areas:(1) the basal cell plasma membrane with its specialized attachment devices or hemidesmosomes, (2) an electron-lucent area, the lamina lucida, (3) the basal lamina, and (4) the sub-basal lamina fibrous components, including anchoring fibrils, dermal microfibril bundles, and collagen fibers. The light microscopic "basement membrane" comprises only the sub-basal lamina fibrous zone. Other cell types, including melanocytes and Merkel cells, are also found at the epidermal-dermal junction. Structures at the junction derive their origin from the epidermis and dermis: the basal lamina is primarily of epidermal origin, the anchoring fibrils of dermal origin. The junction serves the following functions: (1) epidermal-dermal adherence, (2) mechanical support for the epidermis, and (3) a barrier to the exchange of cells and of some large molecules across the junction.

Hepes simplex usually presents with fairly characteristic skin lesions that are localized to small area. A less well appreciated presentation for herpes simplex is a varicelliform eruption that may be difficult to differentiate from chickenpox. We treated a patient with such an eruption who had systemic lupus erythematosus and was receiving oral prednisone. We also review seven other cases from the literature of varicella-like herpes simplex and discuss the role played by immuno-suppression in herpetic infections.

We encountered an unusual case of pemphigus foliaceus in which there were early clinical signs of dermatitis herpetiformis with eosinophilic spongiosis histologically. Numerous authors have appreciated that eosinophilic spongiosis occurs in early pemphigus foliaceus, usually in the preacantholytic stage when the lesions may clinically simulate dermatitis herpetiformis. Recognition of eosinophilic spongiosis may help differentiate early pemphigus from other vesiculobullous disorders.

Evidence supporting an immune complex pathogenesis of bullous lesions in systemic lupus erythematosus includes immune deposits, acute inflammation, and blister formation at the cutaneous basement membrane zone. Since cutaneous immune deposits are a general feature of lupus, an attempt has been made to determine whether deposits in lupus patients with blisters are functionally different from those in patients without blisters. Skin was obtained from 4 consecutive patients with blisters and 14 controls. The groups were matched for clinical and serologic features, duration and activity of disease, and treatment. Skin was examined by direct immunofluorescence for immune deposits and by the leukocyte attachment assay for quantification of complement-activating immune complexes. Clinically normal, viable skin from 1 patient with blisters and 1 patient without blisters was incubated in organ culture with normal human leukocytes and serum complement. All patients in both groups had immune deposits at the basement membrane zone with an equivalent incidence of the major Ig classes. Deposits in patients with blisters were slightly more intense and a linear pattern of fluorescence seen in 75% of these patients was not seen in controls. The leukocyte attachment assay showed significantly greater (p less than .02) cell attachment in patients with blisters (mean = 167) than in patients without blisters (mean = 64) and greater cell attachment in peribullous than normal skin from the same patient. Organ culture showed complement-dependent migration of leukocytes and histologic features similar to those in spontaneous lesions in skin from the patient with blisters but not in skin from the patient without blisters. These results provide evidence supporting immune complex and complement-dependent inflammation in the pathogenesis of bullous lesions in systemic lupus erythematosus.

Rapid advances have occurred in the characterization of human papilloma virus (HPV) types applying the new advanced techniques of restriction endonuclease analysis and molecular hybridization to human wart virus. Human papilloma virus can no longer be viewed as a single, homogeneous virus producing all varieties of clinical warts. At least three antigenically heterogeneous HPV types have been associated with common and plantar warts. Two additional HPV types have been found in patients with epidermodysplasia verruciformis. Condylomata acuminata and laryngeal papillomas contain viruses which are also distinct from the preceding viruses and may represent additional HPV types. This antigenic heterogeneity of HPV has important implications concerning the immunology of human warts which have not been taken into account in most previously published studies. Both antibody and cell-mediated responses may be seen in patients with active warts, but many patients with warts have no demonstrable immune reactions. The role of immunity in wart regression remains poorly understood. Nevertheless, the increased frequency of warts in patients receiving immunosuppressive drugs and with immune deficiency states and the immunologic alterations which occur in patients with regressing or cured warts compared to patients with active warts, particularly the increased frequency of cell-mediated responses and antibodies specific for viral antigens, support a possible role for immunity in the resolution of warts. The evidence to date, however, does not prove that immune mechanisms are directly responsible for the elimination of warts.

Because of latency and infectious recurrences, eradication of herpes simplex and herpes zoster from the world by vaccines is likely to be much more difficult to accomplish than eradication of smallpox. For some time we may have to settle for control of these diseases rather than their eradication. The live, attenuated varicella vaccine protects immunocompromised and normal persons against clinical chickenpox but it does not completely prevent subsequent infection with natural chickenpox virus or latency. With herpes simplex vaccines we may have to be satisfied with amelioration or control of clinical infections and diminution of latency and recurrent disease. Varicella zoster immune globulin plays a useful role in attenuation of varicella in immunocompromised or special-risk persons exposed to varicella zoster virus. Passive immunization for herpes simplex (herpes simplex immune globulin or other antibody preparations) has been studied very little. Maybe passive immunization will have a place in future therapies, especially for serious herpes simplex virus infections in immunocompromised hosts.

A case of multiple clear cell acanthomas is described with a review of the literature. This benign glycogen-rich epidermal tumor is generally unable to accept melanin and lacks phosphorylase or cytochrome oxidase activity. However, the basement membrane zone appears antigenically normal, as documented by the presence of epidermolysis bullosa acquisita antigen, bullous pemphigoid antigen, heparan sulfate proteoglycan, type IV collagen, and laminin by immunofluorescence microscopy.

A persistent shortage of full-time faculty exists in dermatology. Despite the addition of 124 new full-time faculty since 1971 through 1972, 136 training programs in 1974 through 1975 were actively seeking 88 new full-time faculty and believed they needed 243. With a net gain of 30 new faculty a year, it will take 2.93 years to add 88 new faculty that are being actively sought and 5.16 years to add 155 more that are urgently needed. During this eight years, demand for new faculty will increase, so that figures of need may remain essentially unchanged in 1982 through 1983 and between 1971 through 1972 and 1974 through 1975. Expertise that was most needed was in immunology, electron microscopy, histopathology, microbiology, and biochemistry; many accept faculty in any area or with no special training. Measures should be taken to attract and retain more dermatologists in full-time academic positions.

The purpose of this investigation was to study the formation and origin of basal lamina and anchoring fibrils in adult human skin. Epidermis and dermis were separated by "cold trypsinization." Viable epidermis and viable, inverted dermis were recombined and grafted to the chorioallantoic membrane of embryonated chicken eggs for varying periods up to 10 days. Basal lamina and anchoring fibrils were absent from the freshly trypsinized epidermis before grafting although hemidesmosomes and tonofilaments of the basal cells remained intact. Basal lamina and anchoring fibrils were absent from freshly cut, inverted surface of the dermis. Beginning 3 days after grafting, basal lamina was noted to form immediately subjacent to hemidesmosomes of epidermal basal cells at the epidermal-dermal interface. From the fifth to the seventh day after grafting, basal lamina became progressively more dense and extended to become continuous in many areas at the epidermal-dermal interface. Anchoring fibrils appeared first in grafts consisting of epidermis and viable dermis at five day cultivation and became progressively more numerous thereafter. In order to determine the epidermal versus dermal origin of basal lamina and anchoring fibrils, dermis was rendered nonviable by repeated freezing and thawing 10 times followed by recombination with viable epidermis. Formation of basal lamina occurred as readily in these recombinants of epidermis with freeze-thawed, nonviable dermis as with viable dermis, indicating that dermal viability was not essential for synthesis of basal lamina. This observation supports the concept of epidermal origin for basal lamina. Anchoring fibrils did not form in recombinants containing freeze-thawed dermis, indicating that dermal viability was required for anchoring fibrils formation. This observation supports the concept of dermal origin of anchoring fibrils.