Comedogenicity of current therapeutic products, cosmetics, and ingredients in the rabbit ear

Cosmetics continue to be used by acne-prone individuals. Often as more acne develops, more cosmetics are applied. In order to protect against this natural tendency, physicians should provide more patient information on the currently available products and ingredients. This presentation is designed to help in that effort. The data presented were gleaned from the rabbit ear assay, which is not an ideal animal model but is the best we have. If an ingredient is negative in the rabbit ear assay, we feel it is safe on the acne-prone skin. A strong, positive ingredient or cosmetic should be avoided. Ingredient offenders include isopropyl myristate and its analogs, such as isopropyl palmitate, isopropyl isostearate, butyl stearate, isostearyl neopentanoate, myristyl myristate, decyl oleate, octyl stearate, octyl palmitate or isocetyl stearate, and new introductions by the cosmetic industry, such as propylene glycol-2 (PPG-2) myristyl propionate. Lanolins continue to be a problem, especially derivatives such as acetylated or ethoxylated lanolins. Our most troublesome recent finding is the comedogenic potential of the D & C Red dyes. They are universally used in the cosmetic industry, especially in blushers. This may explain the predominance of cosmetic acne in the cheekbone area. All of these D & C Red dyes tested to date, the xanthenes, monoazoanilines, fluorans, and indigoids, are comedogenic. Actually, this is not surprising as they are coal tar derivatives. The natural red pigment, carmine, is noncomedogenic and can serve as a substitute for D & C dyes in blushers. Many finished products are comedogenic. Most troublesome to the dermatologists are the therapeutic tools that we use, such as Liquimat, Retin-A cream, Hytone, Staticin, Sulfoxl, Desquam-X, and Persadox HP cream. These should be reformulated. We have been unable to confirm that precipitated sulfur (U.S.P.) is a potent comedogen in the rabbit ear assay. Clinically, we still find sulfur quite effective as an adjuvant to the benzoyl peroxide therapy for the treatment of acne vulgaris. We would suggest that the bias against sulfur be reconsidered.     

Therapy of pemphigus

Pemphigus is a serious autoimmune skin disease associated with a high morbidity and a significant mortality rate. Prior to the advent of steroid therapy, mortality rates of 70–100% were reported.¹ With the use of corticosteroids and antibiotics, the mortality associated with pemphigus has dropped to 15–44%.^2,3 Currently, where corticosteroids are used in conjunction with immunosuppressives, the mortality rate is approximately 10–20%.⁴

Therapy of a pemphigus patient should include a thorough systematic evaluation. Accurate diagnosis, using clinical, histologic and immunofluorescent parameters, is important because the chemotherapy used can cause severe side effects, and untreated, active pemphigus can be fatal. Exogenous causes of pemphigus, especially drugs,⁵ like penicillamine⁶ and captopril,⁷ should be ruled out. Diseases associated with pemphigus should be considered in the evaluation of the patient.

The exact chemotherapy that should be used to treat each patient optimally is unclear. It is well recognized that corticosteroids are the most helpful agents in many patients, and the drugs of choice in severe or active disease.^8–10 However, severe and often life-threatening side effects are also associated with the prolonged administration of the high doses of corticosteroids used to treat pemphigus.^11,12 Alternative or adjuvant therapies are being used more frequently. This is an attempt to gain control of severe disease not controlled with corticosteroids,^13,14 to reduce maintenance steroid dose,^12,16 or to eliminate steroid therapy in mild disease in order to prevent the long-term side effects of corticosteroids.^9,16

At present at least eight therapeutic modalities have been reported as being effective in therapy of pemphigus: systemic corticosteroids; the immunosuppressive drugs, methotrexate, azathioprine, clyclophosphamide; gold; dapsone; sulfapyridine; and plasmapheresis. Emperic use of these therapies has yielded useful information. Since no prospective or retrospective controlled studies have been done to evaluate the effectiveness of one type of therapy versus another, the optimal combination of these therapies is currently not known.     

Cellular and molecular mechanisms in wound healing: selected concepts

The interactions among cells, structural and other proteins, and large and small molecules in the dermis is an extremely complex, and largely unknown subject in normal skin, so that these interactions in wounded skin are incapable of complete comprehension at present. The problem is compounded by the further reaction and interaction of formed structures within the dermis, such as blood and lymphatic vessels and nerves of all types, and adnexal structures, as well as interactions with the epidermis, which are separately reviewed in the following chapter. In spite of all of this, there are several areas in which research has provided rather extensive insight into the wound healing process. These areas will now be reviewed. A separate review has been provided in this volume of the results obtained using in vitro systems for studies of the wound healing process (Chapter 6).Wound healing has been traditionally divided into three phases: (1) the inflammatory phase, also known as the exudative, lag, or substrate phase; (2) the fibroblastic phase, also known as the connective tissue or proliferative phase; and (3) the remodeling phase, also known as the resorptive or differentiating phase. Although these phases are somewhat arbitrary, we will use them to organize our approach to the problem, dividing our discussion into the inflammatory phase—to which we shall give emphasis—and later developments. Various aspects of the phases of wound healing overlap extensively.     

Anatomie,Biologie, Physiologie und Grundzüge der Pathologie des Nagelorgans

The nail is the largest skin appendage. It grows continuously through life in a non-cyclical manner; its growth is not hormone-dependent. The nail of the middle finger of the dominant hand grows fastest with approximately 0.1 mm/day, whereas the big toe nail grows only 0.03–0.05 mm/d. The nails’ size and shape vary characteristically from finger to finger and from toe to toe, for which the size and shape of the bone of the terminal phalanx is responsible. The nail apparatus consists of both epithelial and connective tissue components. The matrix epithelium is responsible for the production of the nail plate whereas the nail bed epithelium mediates firm attachment. The hyponychium is a specialized structure sealing the subungual space and allowing the nail plate to physiologically detach from the nail bed. The proximal nail fold covers most of the matrix. Its free end forms the cuticle which seals the nail pocket or cul-de-sac. The dermis of the matrix and nail bed is specialized with a morphogenetic potency. The proximal and lateral nail folds form a frame on three sides giving the nail stability and allowing it to grow out. The nail protects the distal phalanx, is an extremely versatile tool for defense and dexterity and increases the sensitivity of the tip of the finger. Nail apparatus, finger tip, tendons and ligaments of the distal interphalangeal joint form a functional unit and cannot be seen independently. The nail organ has only a certain number of reaction patterns that differ in many respects from hairy and palmoplantar skin.     

Role of the epidermis and other epithelia in wound healing: selected concepts

In its normal state, the epidermis is a complex organ in which several cell types, including keratinocytes, Langerhans cells, and melanocytes coexist and interact in complex ways about which little is currently known. The keratinocytes undergo, first, cell division in the deeper layers of the stratum malpighii, then active migration and differentiation to rearrange themselves in the stratum granulosum for final differentiation into keratinized cells. The process by which these cells migrate in an orderly fashion from the undulating dermal-epidermal interface to the flat interface with the keratinized layer is not understood. It is known that few of the basalar cells are undergoing replication at any one time, so that a large, reserve “G^O” pool of cells exists.When there is an injury to the epidermis so that, for example, a portion is removed without damage being done to the dermis, the cell migration pattern changes, so that an increased number of keratinocytes is produced to replace those that have been damaged, killed, or removed. The kinetics of this process is, however, poorly characterized. Also, in states of inflammatory or metabolic injury to the epidermis, there are marked changes, again rather poorly characterized, in epidermal cell migration patterns, which often produce the parakeratotic crust and scale characteristic of many of those pathologic states. Finally, there are diseases—of which the prototype is psoriasis—in which there is a marked change in cellular proliferation and differentiation that, itself, constitutes or produces the major manifestations of the disease. Although the kinetic considerations in psoriasis have been well studied, the studies are difficult to interpret and questions regarding them abound. Recently this problem in nonwounded skin has been reviewed and critically analyzed by Gelfant.¹We face a large number of uncertainties about the division, migration, and differentiation of keratinocytes in normal, damaged, or pathologically altered epidermis. Further, there are many unanswered questions regarding other epidermal cell types, their interactions with each other and with keratinocytes, and the chemical and other signals that mediate those interactions. Thus, the problem of analyzing the role of the epidermis in wound healing, in which there is damage to the dermis as well as to the epidermis, becomes difficult, if not insolvable. Nevertheless, there are rather extensive experimental data regarding several aspects of the problem, including changes in cell morphology, mechanisms of cell migration, kinetics and patterns of cell migration, and factors controlling cell division. Some of these data on the role of the epidermis in wound healing will now be briefly examined.     

Photochemotherapy in cutaneous T cell lymphoma and parapsoriasis en plaques. Long-term follow-up in forty-three patients

Forty-three patients with clinical plaque- and tumor-stage mycosis fungoides, the erythrodermic/Sézary syndrome variant of mycosis fungoides, and parapsoriasis en plaques were treated with oral psoralens and ultraviolet A (PUVA). Pretreatment skin biopsies, evaluated by light microscopy, revealed seventeen diagnostic, seventeen suggestive, and nine nonspecific specimens. Clinical and histologic parameters were followed for an average of 38.4 months (range, 4-67 months). Twenty-five patients had complete clearing, and fourteen did not respond. Most patients in the complete-response group had either plaque lesions of mycosis fungoides or parapsoriasis en plaques prior to PUVA. Most patients in the no-response group had either tumor lesions or the erythrodermic/Sézary mycosis fungoides at the start of PUVA. In the no-response group the treatment modalities used prior to PUVA were twice the number used in the complete-response group. Patients in the complete-response group had clearing of their lesions after an average PUVA dose of 117 joules/cm2. Relapse occurred in seventeen patients after an average remission time of 6.3 months and responded to additional PUVA. Patients whose skin remained clear after the first course of PUVA continued to have clear skin for up to 58 months, with an average complete remission of 29.5 months by the end of the study period. Histologic evaluation before PUVA and at clearing revealed a definite trend toward a normal microscopic picture, but at least a mild inflammatory infiltrate usually persisted. At the end of the study period, the lesions of ten patients had entirely cleared for an average of 44 months, the lesions of five had cleared during a second course of PUVA, five had stable limited-plaque disease while receiving maintenance PUVA, eleven were undergoing electron beam radiation therapy or chemotherapy for progressive disease, ten had died, and two patients were lost to follow-up. Therefore, in the early stage of mycosis fungoides, PUVA may induce significant disease-free intervals. Prior treatment with a variety of modalities, the patient's age, and/or the duration of disease may affect response to PUVA.     

Laboratory diagnosis of herpes simplex virus type 1 and type 2 infections

Herpes simplex virus (HSV) is known to infect several body sites. Most commonly HSV infection results in lesions around the mouth or in the genital area. Infection at these sites may also be subclinical. Over the past decade HSV has been increasingly recognized as an important cause of both mild and severe diseases in a wide range of patients. Two distinct types of HSV are known, HSV-1 and HSV-2, and many antigens are shared between the two. Infection with either type of virus can occur early in life, although infection with HSV-2 becomes common only after puberty. The most common manifestation of HSV-1 infection is the orofacial “fever blister,” while HSV-2 is most often responsible for genital lesions.^1,2 Either virus type can, however, cause disease in almost any site of the body and can recur frequently. This recurrence of disease from an inapparent or latent state makes HSV infection unique among the common viral infections.Mistakes in diagnosis of HSV infections based on clinical findings alone are not uncommon. Herpetic lesions have been confused with allergic reactions, drug reactions, and lesions due to other infectious agents. Besides the medical importance of HSV in special situations, the social impact of having “herpes” is of considerable concern is almost everyone. Therefore, precise diagnosis of HSV infection is of paramount importance, particularly since effective antiviral therapy is available for many forms of the disease.Morphologically, all herpesviruses are alike (Fig. 1); therefore, it is not possible to differentiate members of the group by their structure alone. Although rapid techniques for diagnosis of HSV infection are constantly being refined and improved, virus isolation in tissue culture is still the most definitive method of detecting HSV, and it is the most widely used. In this chapter detailed procedures for HSV isolation and typing are described, with brief reviews on methods that have been used in conjunction with virus isolation when cell culture facilities are not available.     

Skin tumors

Most skin tumors can and do occur on the lower limbs, although some, such as papillary adenoma of the nipple and organoid nevus (nevus sebaceus of Jadassohn), are almost never seen at this site. The present discussion will be limited to selected tumors that occur most commonly on the lower extremities. It is important to recognize some neoplasms, e.g., acral-lentiginous melanoma, before they actually develop into tumors in the morphologic sense. It is also helpful to recognize that not all tumors (i.e., nodular swellings) are neoplastic, e.g., tungiasis. To this end, pathologic examination is essential and will be emphasized in this report.     

The soap chamber test. A new method for assessing the irritancy of soaps.

The chamber test for assessing the irritancy of soaps entails five weekday exposures to 8% solutions with readings of scaling, redness, and fissuring on the following Monday. Eighteen well-known toilet soaps were evaluated. Great differences were noted. Most had an appreciable irritancy potential. These results contrast with a number of studies which failed to show differences among soaps or which concluded that soaps were innocuous.     

Closure of simple heel ulcers by skin stretching

A majority of heel ulcers, at least to begin with, extend to dermis or to the fat pad in its superficial part and an appropriate skin closure can heal these ulcers as most of the padding is in tact. Since the skin is adherent to the deeper structures with fibrous bands it has to be stretched or undermined (by cutting the fibrous bands) to close the wound without tension. 17 feet in 11 patients (10 males; one female) in the 12-54 year age-group were operated upon and followed up. Because skin is adherent to deeper tissues by fibrous septae, stretching of skin was planned to mobilize it for a tension-free closure. Of the 17 feet, 13 could be re-examined after 30 months or more. Most of the minor recurrences were seen in the first 6 months after surgery. Major recurrences were seen in 2 feet (one case). The suture line did not show hyperkeratosis and the scar merged well into the surrounding skin after one year. Available data suggest that simple heel ulcers can be made to heal with a good scar by skin-stretching and suture, and, by radiography of the foot, it is worth separating those cases in which ulcer is not extending deep involving calcaneum. The size of the ulcer in heel is important for the success of the operation. The procedure is not intended for big wounds (>15 mm in width).     

Intravenous immunoglobulin as adjunct therapy for refractory pyoderma gangrenosum: systematic review of cases and case series

Pyoderma gangrenosum is an uncommon skin condition in which white blood cells, neutrophils, infiltrating the skin lead to destruction and ulceration. Because early treatment is a logical approach to reducing this damage, various different treatment methods have been tried including the use of immunoglobulin, a protein extracted from blood plasma containing antibodies, given by intravenous injection (IVIG). This study is a review of previously published studies using this technique. The authors from Harvard and hospitals in Boston, U.S.A., identified 49 patients who had received this treatment after the failure of other therapies, such as oral corticosteroids and cyclosporine, to improve the condition. Most had at least one underlying disease including cancer or inflammatory bowel disease such as ulcerative colitis. The skin damage affected different body sites such as the lower limbs or trunk. In most cases the patients were also receiving oral corticosteroids at the time of the IVIG treatment. Over half the patients responded completely to the treatment with IVIG in addition to steroids, with a substantial number of the remainder responding in part to this therapy. The most common side effect was nausea or headache although rashes and fever were also seen. Overall these results suggest that it is a potentially useful therapy for patients who have not responded to other medications used to treat this condition.     

Superior nuclear receptor selectivity and therapeutic index of methylprednisolone aceponate versus mometasone furoate

Although introduced more than 50 years ago, topical glucocorticoids are still the first line therapy for many inflammatory skin disorders such as atopic eczema, contact dermatitis and many others. Recently, significant improvements have been made to optimize the ratio of desired to unwanted effects. While with early compounds such as triamcinolone, topical side effects such as skin atrophy and telangiectasias can be observed rather frequently, newer drugs such as methylprednisolone aceponate or mometasone furoate have a significantly improved therapeutic index. The present study compared these two modern topical glucocorticoids, which possess the highest therapeutic index currently found, in terms of nuclear receptor selectivity in vitro and induction of the most important local side effects (skin atrophy and telangiectasias) in a relevant rodent model in vivo. We demonstrate that methylprednisolone aceponate displays higher specificity in nuclear receptor binding compared with mometasone furoate. Methylprednisolone aceponate was also markedly superior in terms of minimizing induction of skin atrophy or telangiectasias when compared with mometasone furoate. Based on these observations, methylprednisolone aceponate is expected to have a greater therapeutic index as compared with mometasone furoate, at least in the test systems used here. The degree to which this observation may translate into a clinical setting requires confirmation.     

History of pemphigus

The modern concept of pemphigus divides it into variants: pemphigus vulgaris, pemphigus vegetans, pemphigus foliaceus, pemphigus erythematosus (Senear-Usher syndrome), and pemphigus herpetiformis. These conditions are all related by the fact that they are all bullous diseases at some time during their clinical course and are histologically characterized by acantholysis. In pemphigus vulgaris and pemphigus vegetans, acantholysis is generally above the basilar cell layer (suprabasilar) or in the lower half of stratum spinosum. In pemphigus foliaceus, pemphigus herpetiformis and pemphigus erythematosus, acantholysis occurs in the granular cell layer or upper stratum spinosum. Autoantibodies to the intercellular cement substance of the epidermis are present in all the variants.

The changes in the concept of pemphigus over time has been reviewed.^1,2 The term “pemphigus,” itself, was first proposed by Boissier de Sauvages in his classification of skin diseases.³ He described pemphigus maior as an acute, febrile, blistering disease lasting only two weeks. Today, the diagnosis would probably be erythema multiforme.

Wichmann^4,5 was the first to describe pemphigus as a chronic bullous disease; he used the term, febris bullosa, to describe bullous eruptions of short duration. Unfortunately, few authors agreed with Wichmann's more restricted concept, and continental dermatologists continued to use the term pemphigus for a wide range of vesicular or bullous diseases. For example, Gilibert,⁶ in his monograph on pemphigus, included almost every disease with bullae in his classification. His “chronic pemphigus” most closely corresponds to the modern concept of pemphigus. Von Martius⁷ had an equally liberal definition of pemphigus, dividing it into 97 types.

Willan had a much more restricted view of the disease. In his classification of skin diseases, pemphigus vulgaris was a febrile, bullous eruption of short duration.⁸ He applied the term “pompholyx duitinus” to a chronic, bullous eruption, without inflammation and fever, similar to the modern concept of pemphigus vulgaris.     

Treatment of skin cancer using multiple modalities

Physicians concerned with modern treatment of skin cancer should be knowledgeable about the indications and contraindications of the five major modalities available for the treatment of skin cancer: electrosurgery, excision and suture closure surgery, radiation therapy, cryosurgery, and Mohs' chemosurgery. Flexibility in the application of these modalities is important if physicians are to offer patients the best method for the treatment of each skin cancer. Selection of the proper treatment method must take into consideration factors of cell type, size and depth, specific anatomic location, duration, primary or recurrent, single or multiple, degree of sun damage to surrounding skin, and age and general health of the patient. This review seeks to define the relative advantages and disadvantages, as well as indications and contraindications, of these five major modalities. This review also seeks to present relative guidelines for choosing treatment methods, including discussions of the previously mentioned factors.     

Graft versus host disease

Graft versus host disease (GVHD) occurs in 50% to 70% of patients receiving bone marrow transplants. It can also develop in immunosuppressed patients with malignancies who receive nonirradiated blood transfusions. Most work indicates that the primary mechanism of GVHD is cell-mediated. It is likely that humoral factors are involved as well. Cutaneous manifestations are the earliest and most frequent sign of the disease. These may be morbilliform, scarlatiniform, lichenoid, or sclerodermoid lesions. In acute GVHD, the skin, gastrointestinal tract, and liver are commonly affected. In chronic GVHD, findings similar to collagen vascular disorders are present. A skin biopsy establishes the diagnosis.     

Hydroquinone 4%, tretinoin 0.05%, fluocinolone acetonide 0.01%: a safe and efficacious 12-month treatment for melasma

This article describes a long-term, multicenter, open-label, 12-month study of once-daily fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05% (Tri-Luma Cream, hereinafter called TC [triple combination]) application in the treatment of melasma. A total of 228 patients with facial melasma were enrolled and treated; 173 patients (76%) completed the study. Most patients had 1 to 2 courses of treatment lasting approximately 6 months in total. TC cream showed a favorable safety profile. only 3 patients (1%) withdrew from the study due to treatment-related adverse events (AEs). A total of 129 patients (57%) experienced at least one treatment-related AE. Most AEs were expected application-site reactions that were mild and transient in nature and did not require remedial therapy. There were no cases of skin atrophy or skin thinning and only 6 cases of telangiectasia (5 mild and 1 moderate), most of which had improved by the end of the study. Results of the efficacy assessments were positive, with both the patient and the physician assessing melasma to be either completely or nearly cleared by the end of the study in more than 90% of cases. In this study, a once-daily application of TC cream over an extended period of 12 months showed no notable safety concerns and offered an effective treatment for melasma.     

Tumor viruses, oncogenes, and human cancer

We review the biology of transforming retroviruses and their relationship to cellular transforming genes (tumor oncogenes). Evidence is discussed for the involvement of a retrovirus in a newly described syndrome, "adult T cell leukemia/lymphoma," which has a high incidence of skin involvement. This virus is related to the animal retroviruses which induce tumors in susceptible hosts after a long latent period. Cellular transforming genes encode proteins which directly change the oncogenic potential of a cell. These genes, which are altered forms of normal cellular genes, have been isolated from a wide variety of human tumors. Viral and cellular transforming genes produce their changes by at least two different mechanisms: abnormally high production of the normal protein encoded by these genes, or normal levels of an altered form of the protein.     

Vitamin D and the skin: an ancient friend, revisited

Most vertebrates need vitamin D to develop and maintain a healthy mineralized skeleton. However, 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D(3)], the biologically active vitamin D metabolite, exerts a multitude of important physiological effects independent from the regulation of calcium and bone metabolism. We know today that the skin has a unique role in the human body's vitamin D endocrine system. It is the only site of vitamin D photosynthesis, and has therefore a central role in obtaining a sufficient vitamin D status. Additionally, the skin has the capacity to synthesize the biologically active vitamin D metabolite 1,25(OH)(2)D(3), and represents an important target tissue for 1,25(OH)(2)D(3). In keratinocytes and other cell types, 1,25(OH)(2)D(3) regulates growth and differentiation. Consequently, vitamin D analogues have been introduced for the treatment of the hyperproliferative skin disease psoriasis. Recently, sebocytes were identified as 1,25(OH)(2)D(3)-responsive target cells, indicating that vitamin D analogues may be effective in the treatment of acne. Other new functions of vitamin D analogues include profound effects on the immune system as well as in various tissues protection against cancer and other diseases, including autoimmune and infectious diseases. It can be speculated that the investigation of biological effects of vitamin D analogues will lead to new therapeutic applications that, besides cancer prevention, may include the prevention and treatment of infectious as well as of inflammatory skin diseases. Additionally, it can be assumed that dermatological recommendations on sun protection and health campaigns for skin cancer prevention will have to be re-evaluated to guarantee a sufficient vitamin D status.     

Electric fields and wound healing

There are many points of view from which one may consider the healing of wounded skin, several of which are dealt with in earlier chapters. We would like to focus on one aspect of wound healing that has received only scant attention: the possible role of electric fields in the migration of epithelial cells that must occur in order to heal wounded skin. This cell migration is one of the earliest signs of epithelial repair of epidermal wounds, both in mammals and in amphibians.¹ One important reason for the lack of attention to electrical aspects of skin healing can be attributed to the paucity of information, useful to an understanding of wound healing, about the mammalian skin's ability to generate electrical currents. The bulk of the literature on the electrical properties of mammalian skin is concerned with psychophysiology.^{2 4}There is some information about electrical properties of skin that may be relevant to wound healing. Some years ago, Herlitzka⁵ confirmed DuBois-Reymond's 1860 observation⁶ that about 1 microampere of current leaves small epidermal wounds made in human fingers when the wounds are immersed in saline. Much more recently. Illingworth and Barker⁷ have found currents with densities ranging from 10 to 30 μA/cm² leaving the stumps of accidentally amputated children's fingertips when the stumps are immersed in saline. We, working with Barker, have added to this information⁸ by studying the current-generating capacity of the glabrous epidermis of the cavy, and, particularly, the gradients of electrical potential that exist in the vicinity of wounds made in such skin. Subsequently, we have begun study of wound healing in a simpler system, larval Xenopus skin. We here will review this information, present some previously unpublished observations, and speculate on the possible relevance of this information to wound healing.     

Pemphigus vulgaris: the manifestations and long-term management of 55 patients with oral lesions

Perhaps surprisingly, the manifestations and management of patients with pemphigus vulgaris and oral lesions have been detailed only infrequently. The present study has examined the clinical features, diagnosis and management of a cohort of 55 patients, including three adolescents, with pemphigus vulgaris predominantly affecting the oral mucosa. There was about a 6-month delay from the onset of symptoms until presentation for diagnosis, longer in men than in women. Patients typically had multiple lesions affecting mainly the buccal and/or palatal mucosae, and over half the patients had lesions affecting non-oral mucosal sites. Nearly one-quarter (24%) had cutaneous involvement. Most patients were otherwise healthy with no other autoimmune disorders. Classical histopathological features of pemphigus vulgaris were present in all patients, as well as IgG intraepithelial deposits in all patients tested and circulating epithelial antibodies in most. Thirty-two patients were treated in the clinic, four responding to topical immunosuppressive therapy, the remainder needing and responding, at least in part, to systemic immunosuppression. Systemic corticosteroids often with adjunctive immunosuppressives, particularly azathioprine, were required in 87% of patients. In 18% of the patients, the disease resolved in 3 months, but 76% had recalcitrant disease. Adverse effects were seen in 78%, and two patients died, at least one as a consequence of immunosuppressive therapy. It is concluded that pemphigus vulgaris affecting the oral mucosa is still diagnosed only after considerable delay because patients, especially men, present late; it has a chronic course; it is often associated with lesions in other mucosae and/or skin; it can be resistant to currently available therapies; and immunosuppressive therapy frequently produces adverse effects, occasionally lethal.