Immunopathology of cicatricial pemphigoid: studies of complement deposition.

Immunopathologic investigations were conducted on the sera and oral mucosal tissue specimens of 23 patients with cicatricial pemphigoid. A linear, continuous basement membrane zone pattern was noted in 83% of oral mucosal biopsy specimens studied. This pattern is indistinguishable from the pattern noted in immunofluorescence studies of bullous pemphigoid, herpes gestationis, and some cases of desquamative gingivitis. Complement studies provided data supportive of classical pathway activation in cicatricial pemphigoid tissue. Deposition of IgA with Factor B, properdin, and C3 raised the possibility of alternative pathway activation, a question requiring further study. Circulating antibasement membrane zone antibodies were noted in the sera of two patients with cicatricial pemphigoid.

Scleromyxedema: a scleroderma-like disorder with systemic manifestations.

Scleromyxedema is a rare fibromucinous connective tissue disorder characterized by papular skin lesions associated with sclerosis and a serum monoclonal gammopathy. Little is known about either the natural history or the systemic manifestations of this disease. We reviewed the medical records of 19 patients with biopsy-proven scleromyxedema seen from 1950 to 1985 for evidence of systemic disease. There were 10 males and 9 females with a median age at diagnosis of 53 years. Monoclonal gammopathy was present in 13 patients. Eight patients complained of dysphagia; 3 had proximal esophageal dysfunction and 1 had total esophageal aperistalsis on barium swallow. Proximal muscle weakness was noted in 5, with an inflammatory myopathy in 3. Six patients complained of dyspnea on exertion. Of these, 5 had reduced diffusing capacity, 3 had reduced volumes, and 2 developed cor pulmonale. Pathologic changes characteristic of "scleroderma kidney" were demonstrated in 1 patient at postmortem. One patient had Raynaud's phenomenon and 2 had arthralgias/arthritis with noninflammatory synovial fluids. Although 8 of 12 patients treated with melphalan noted regression of their skin changes, no consistent improvement in the extracutaneous manifestations was demonstrated. Furthermore, 2 patients died of sepsis related to melphalan-induced myelosuppression, and 4 developed hematological malignancies following melphalan therapy. In conclusion, systemic manifestations in scleromyxedema are more prevalent than previously recognized, and can resemble those of scleroderma. Significant toxicity occurred with the use of alkylating agents in these patients, with treatment-related complications developing in 45% of patients treated with melphalan. The lack of definitive data regarding the natural history of this disease complicates the question of optimal therapy, but the use of alkylating agents should be reserved for those patients with severe debilitating skin disease.

Population-based study of herpes zoster and its sequelae.

The epidemiology of herpes zoster and its sequelae have been investigated in a community-based study. The incidence rates observed in Rochester, Minnesota, are lower than those determined in practice-based series; and this may reflect some selectivity in practice-based series compared to population-based studies. No significant sex difference or seasonal variation was observed but the incidence did increase markedly with age. An increase in incidence was also observed over the 15-year period studied. The dermatomal distribution of herpes zoster observed in Rochester was quite similar to previous studies, despite their inherent biases in case ascertainment, except for a lower proportion with cranial nerve zoster. Herpes ophthalmicus (V1) appears to affect a slightly different population than zoster of the other dermatomes, with elderly males being more at risk. Also, herpes ophthalmicus is associated with a higher complication rate compared to the other dermatomes primarily due to the fragility of the involved organ. The elderly are also at greatest risk for the most common complication, post-herpetic neuralgia. The rate of PHN is not significantly increased in any particular dermatome but is significantly decreased in lumbar herpes zoster.

Generalized elastolysis (cutis laxa).

Generalized elastolysis is a rare and unique systemic disorder of connective tissue in which the elastic fibers suddenly become fragmented, disorganized and fewer in number with the resultant production of such entities as cutis laxa, emphysema, aortic aneurysms and bowel diverticula appearing in the organ system involved, that is, skin, lung, vasculature or gastrointestinal tract. Presented here are three cases that, illustrate the typical features of this condition. In addition, 14 more cases were retrieved from the literature and the information reviewed. Various etiologic factors relating to the synthesis and degradation of elastic tissue are discussed in light of recent findings in the biochemistry of connective tissue.

Herpes gestationis.

Herpes gestationis is a rare, pruritic, blistering disease of the skin that occurs in pregnancy and the puerperium. Its recognition by those caring for the pregnant patient is important in determining appropriate care for the patient and in alerting the physician to possible effects on fetal outcome. Understanding of this disease has been rapidly expanding, and these advances are reviewed here through the use of an illustrative case report and a review of the literature. The evidence for significant risk of fetal morbidity and mortality, the potential indicators in patients who are at high risk, and the treatment approaches are stressed.

Incidence and trend of herpes progenitalis. A 15-year population study.

A population-based epidemiologic study of herpes progenitalis was conducted in residents of Rochester, Minnesota, for the 15-year period 1965 through 1979. Three hundred ninety-two patients (129 males, 263 females) were identified. The average annual incidence rate of herpes progenitalis was 50 per 100,000 population. A continuous increase in incidence was demonstrated throughout the study period (P less than 0.0005, trend test). In 1979, the incidence peaked at 128 per 100,000 population. The median age at onset was 24 years, and more than 80% of the patients were 18 to 36 years of age. Females predominated by 1.5:1 (P less than 0.001) and were, on the average, 4 years younger than the male patients. Although 15 pregnancies in the series were affected by herpes progenitalis, no neonatal herpes was noted, nor was the number of unfavorable outcomes of pregnancy unusual. No invasive or in situ genital carcinoma developed in patients after 1,544 person-years of follow-up.

Malignant pyodermas revisited.

The concept of malignant pyoderma (MP) has created controversy since its origin. The distinction of this disease from pyoderma gangrenosum was based on clinical criteria and response to treatment. Herein we discuss our current ideas on this entity and its possible relationship to Wegener's granulomatosis (WG). Follow-up data from the three original cases of MP are reported, as well as additional clinical and laboratory data from cases subsequently thought to represent MP. Many of these cases have similar clinical features such as facial and periauricular ulceration and occasionally signs or symptoms of WG, including positive titers of antineutrophil cytoplasmic antibodies (with a diffuse cytoplasmic staining pattern) (cANCA). MP represents a distinctive clinical disorder and may be a dermal manifestation of WG. Some cases of MP may represent pyoderma gangrenosum or other undefined systemic illnesses. Such cases of WG can be distinguished on the basis of clinical, histopathologic, and laboratory evidence including cANCA titers. MP should no longer be used as a final clinical diagnosis.

Pyoderma gangrenosum in childhood.

A review of our records disclosed eight children with pyoderma gangrenosum. All had associated inflammatory bowel disease, and four had arthritis. In three patients the bowel disease was severe and required resection of portions of the affected bowel. The cutaneous lesions had a chronic course (average duration, 2 1/2 years), and systemic therapy was required in seven cases. Previously reported cases of pyoderma gangrenosum in children are reviewed, and the management of this skin disorder in childhood is discussed.

A diffuse pustular eruption associated with ulcerative colitis.

Two patients each with a two-year history of chronic ulcerative colitis developed, over a 24- to 48-hour period, painful pustules involving the skin and oral mucosa. The pustular eruption was associated with a severe exacerbation of the colitis. Culture of the lesions and of the blood failed to reveal an infectious cause for the eruption. Histologic study of a pustule in case 2 revealed suppurative folliculitis. The lesions subsided rapidly in case 1 when intravenous hydrocortisone and intravenous and intramuscular antibiotics were administered, and further resolution occurred after colectomy. A similar rapid resoultion of the pustules occurred in case 2 after initiation of treatment with intramuscular cortisone acetate and antibiotics and with colectomy. This pustular eruption may represent a variant of pyoderma gangrenosum.

Beaded fluorescence pattern of FTA-ABS test associated with malignancy.

A beaded pattern of immunofluorescence (IF) occasionally occurs in routine FTA-ABS testing. This phenomenon strongly correlates with false-positive reactions in patients with SLE. We report on this IF finding in association with carcinoma of the colon.

Blastomycosis-like pyoderma.

Seven patients with blastomycosis-like pyoderma had skin lesions of four months' to six years' duration. The criteria for the diagnosis of blastomycosis-like pyoderma include the clinical presentation of large verrucous plaques with multiple pustules and elevated border, pseudoepitheliomatous hyperplasia with abscess histologically, and the growth of at least one pathogenic bacteria from the culture of a tissue-biopsy specimen. The differential diagnosis includes deep fungus infection (especially North American blastomycosis), bromoderma, pyoderma gangrenosum, mycobacterial infections, giant keratoacanthoma, and squamous cell carcinoma. Generally, the patients had one or more conditions that could have affected their systemic or local immunologic competence to infection. We believe that the clinical and histologic features in these cases of blastomycosis-like pyoderma were produced by an unusual, exaggerated, vegetating-tissue reaction to a primary or secondary bacterial infection.

Subcorneal pustular dermatosis and pustular psoriasis. A clinicopathologic correlation.

The relationship between subcorneal pustular dermatosis (SCPD) and pustular psoriasis is discussed on the basis of a study of 23 patients with SCPD seen at the Mayo Clinic, Rochester, Minn, since 1956. In seven of the 23 patients, pustular psoriasis subsequently developed, and in three other patients there was associated psoriasis vulgaris. It was impossible to make a histopathologic distinction between SCPD and some cases of pustular psoriasis. The response to therapy with sulfones was erratic, if not ineffective. Our data suggest that disease identical to SCPD is, in many instances, strongly associated biologically, clinically, and histopathologically with psoriasis, and that continued observation of the clinical course may further substantiate this relationship in many cases.

Condyloma acuminatum in Rochester, Minn., 1950-1978. I. Epidemiology and clinical features.

From 1950 through 1978, condyloma acuminatum was diagnosed in 746 residents of Rochester, Minn (246 male and 500 female subjects). With the number of cases increasing almost every year until 1975, the mean annual incidence rate reached 106.5 per 100,000 population in the period 1975 through 1978, apparently the highest reported to date. Among age groups, the rate was highest in the 20- through 24-year-old group. Female patients contracted the infection at a higher rate and at a younger age than male patients. Anal condyloma occurred in one third of the male subjects studied and recurrent condyloma in 30% of the male subjects. More female than male patients had lesions at multiple locations.

Condyloma acuminatum in Rochester, Minn, 1950-1978. II. Anaplasias and unfavorable outcomes.

A total of 746 patients residing in Rochester, Minn, received the diagnosis of condyloma acuminatum between 1950 and 1978. Anaplasia was present in six and subsequently developed in 36 patients during follow-up examination in 42 patients (one male and 41 female). One had invasive squamous cell carcinoma (vulva), six had severe dysplasias, 21 had moderate to mild dysplasias, and 14 had carcinomas in situ (CIS), of which 11 were cervical. In the female patients, 37 of the anaplasias were cervical and the other four were vulval or vaginal. The 11 cervical CIS amounted to 3.8 times the expected number of 2.9, based on an earlier study of cervical cancer incidence in the community. The risk of cervical CIS developing among patients with condyloma is significantly higher than expected. Neither laryngeal papilloma nor other unfavorable outcomes substantially affected the conceptus of 51 pregnancies in women with concurrent condyloma. There appears to be an association between condyloma and genital malignant neoplasms and a relationship of condyloma with sexually transmitted disease and warts.

Pyoderma gangrenosum and monoclonal gammopathy.

The records of eight patients with pyoderma gangrenosum and monoclonal gammopathy showed that all patients except one had an IgA paraproteinemia. To date, seven patients have had a benign course and multiple myeloma has developed in one. In seven patients, the onset of the pyoderma gangrenosum preceded the detection of the monoclonal gammopathy. The monoclonal gammopathy did not seem to influence the morphologic findings, course, or therapy of the pyoderma gangrenosum. In the one patient with myeloma, treatment of the myeloma caused accelerated healing of the skin lesions.

Skin cancer in patients with psoriasis treated with coal tar. A 25-year follow-up study.

For many years, crude coal tar has been used for the treatment of psoriasis. The possible carcinogenic effect of crude coal tar and ultraviolet (UV) radiation (Goeckerman regimen), considered individually or in combination, has been of some concern to physicians. A 25-year follow-up study was completed on 280 patients with psoriasis who were hospitalized and treated with crude coal tar and UV radiation at the Mayo Clinic, Rochester, Minn, during the years 1950 through 1954. The results of this study suggest that the incidence of skin cancer is not appreciably increased above the expected incidence for the general population when patients are treated with coal tar ointments. It seems that the Goeckerman regimen (topical crude coal tar combined with UV radiation) can be used with minimal risk for skin cancer in the treatment of psoriasis.

Treatment of scleromyxedema with melphalan.

Scleromyxedema is an uncommon cutaneous fibromucinous disease with a monoclonal protein, which has resisted a number of therapies. Eight cases followed up for as long as 12 years have provided an opportunity to observe the effects of melphalan treatment in this disease. The fibrohistiocytic and mucinous change of the skin in scleromyxedema and often the monoclonal protein can be controlled by low-dose chemotherapy. Although melphalan does not usually produce clinical toxic effects of importance, it is a myelotoxic drug and cytopenia is common; one patient died of acute myelomonocytic leukemia after ten years of successful therapy of the scleromyxedema, thus implying that long-term therapy may be dangerous by itself. These patients require close supervision. Leukocyte and platelet counts must be performed every three weeks, and the dosage of melphalan adjusted accordingly.

Incidence of psoriasis in Rochester, Minn, 1980-1983.

This population-based study was carried out using the medical records linkage data resource for the population of Rochester, Minn, at Mayo Clinic. There were 132 newly diagnosed cases of psoriasis identified during a 4-year period (1980 through 1983); 88% of the cases had been seen and diagnosed by a dermatologist. The overall crude incidence rate was 57.6 per 100,000 population; for men and women, the rates were 54.4 and 60.2, respectively. The overall sex- and age-adjusted (1980 US white population) incidence rate was 60.4 per 100,000 person-years. The highest rate of occurrence (112.6) was in the 60- to 69-year-old age group. Most of the cases of psoriasis diagnosed in this study (58%) were mild, and the patients had psoriatic lesions on less than 10% of their body. There are no other published incidence rates for this condition with which to make comparisons.

Idiopathic gingivostomatitis.

Atypical gingivostomatitis is recognized by a combination of clinical findings, a sharply marginated, deep red edematous quality to the attached gingiva, angular cheilitis, and a sore red tongue. Unfortunately, there are no general laboratory tests that are diagnostic of the condition, although biopsy of the gingiva shows a marked plasma cell infiltrate. The etiology remains obscure, although chewing certain gums or using some types of dentifrices precipitates the problem. The disease seems to involute spontaneously in some patients. Treatment is symptomatic.

Pruritus ani: could it be malignant?

The management of extramammary perianal Paget's disease should include a careful search for an associated carcinoma in the pelvic viscera by means of proctoscopy and x-ray. Such local malignancies as Bowen's disease, which may be pigmented and multifocal in this region, and invasive squamous cell carcinoma may first manifest themselves as pruritus ani.