Etiology

Ectodermal dysplasia syndrome results from aberrant development of ectodermal derivatives in early embryonic life. Genes responsible for the varied syndromes are located on different chromosomes and may be mutated or deleted.

Clinical Features

Individuals affected by EDS have abnormalities in different structures. Some EDS types are mild, while others are devastating. EDSs have been reported most often in whites, but they have also been observed in persons of other races. X-linked hypohidrotic ED has full expression only in males. Female carriers outnumber affected men, but females show little or no signs of the condition. The remaining EDSs have no gender predilection. Obvious manifestations of the disorders are not clinically apparent in newborns. Dental, hair, and nail anomalies are evident during infancy or childhood. The number of hair follicles, sweat glands, and sebaceous glands varies. Symptoms of a reduction in hair follicles vary from sparse scalp hair (usually short, fine and dry) to a complete absence of hair. Hair bulbs may be distorted, bifid, and small. Eccrine sweat glands may be absent or sparse and rudimentary, particularly in those with hypohidrotic EDS. In some cases, mucous glands are absent in the upper respiratory tract and in the bronchi, esophagus, and duodenum. The mouth may be dry from hypoplasia of the salivary glands; lacrimal glands also may be deficient. Teeth show abnormal morphogenesis or are absent. Nails are often brittle and thin or show abnormal ridging, but they may be grossly deformed. Other signs and symptoms like lack of breast development, deficient hearing or vision, cleft lip and/or palate and missing fingers or toes are also seen. The presence or absence of these abnormalities defines the different syndromes. Following are the best-defined syndromes within this group.

Hypohidrotic (anhidrotic) ED (Christ-Siemens-Touraine syndrome) is the most common phenotype in this group and is usually inherited as an X-linked recessive trait; autosomal recessive and autosomal dominant forms have been reported but are rare. It is characterized by several defects (e.g. hypohidrosis, anomalous dentition, onychodysplasia, hypotrichosis). Typical facies are characterized by frontal bossing; sunken cheeks; saddle nose; thick, everted lips; wrinkled, hyperpigmented skin around the eyes; and large, low-set ears. Because such characteristics are not obvious at birth, clinical clues for diagnosis in the neonatal period are extensive scaling of the skin and unexplained pyrexia. Dental manifestations include conical or pegged teeth, hypodontia or complete anodontia, and delayed eruption of permanent teeth. The prevalence of atopic eczema is high. Other common signs are short stature, eye abnormalities, decreased flow of tears and photophobia. Intelligence is normal.

Oral Manifestations

The oral findings are of particular interest, since patients with this abnormality invariably manifest anodontia or oligodontia, complete or partial absence of teeth, with frequent malformation of any teeth present, both deciduous and permanent dentitions (Fig. 19-1B and C). Where some teeth are present, they are commonly truncated or cone shaped. It should be pointed out that even when complete anodontia exists, the growth of the jaw is not impaired. This would imply that the development of the jaws, except for the alveolar process, is not dependent upon the presence of teeth. However, since the alveolar process does not develop in the absence of teeth, there is a reduction from the normal vertical dimension resulting in the protuberant lips. In addition, the palatal arch is frequently high and a cleft palate may be present (Fig. 19-2).

According to Bessermann-Nielsen, the salivary glands, including the intraoral accessory glands, are sometimes hypoplastic in this disease. This results in xerostomia, and the protuberant lips may be dry and cracked with pseudorhagades formation. As a related phenomenon, there may be hypoplasia of the nasal and pharyngeal mucous glands which leads to chronic rhinitis and/or pharyngitis, sometimes with associated dysphagia and hoarseness.

Hidrotic ED (Clouston syndrome) is inherited in an autosomal dominant manner; the homozygous state may be lethal. Clinical features include nail dystrophy associated with hair defects and palmoplantar dyskeratosis. Nails are thickened and discolored; persistent paronychial infections are frequent. Scalp hair is very sparse, fine, and brittle. Eyebrows are thinned or absent. Patients have normal facies, normal sweating and no specific dental defect is seen.

Histologic Findings

Skin histopathology documents the reduction in the number of sweat glands, hair follicles, and sebaceous glands associated with the different syndromes. In hypohidrotic EDS, the epidermis is thin and flattened. Eccrine sweat glands are few or poorly developed or are very rudimentary. Beyond the skin, mucous glands in the upper respiratory tract and bronchi are often reduced in number. Salivary glands may show ectasia of ducts and inflammatory changes.

Treatment

There is no treatment for the condition; however affected individuals with dental defects could be subjected to early dental evaluation and intervention beginning with dentures as early as two years.

Clinical Features

Chondroectodermal dysplasia is characterized by a number of ectodermal disturbances, including involvement of the nails and teeth as well as chondrodysplasia, polydactyly and sometimes congenital heart disease.

The nails are generally hypoplastic with marked koilonychia. The sweat mechanism has been reported to be normal in contrast to that in hereditary anhidrotic ectodermal dysplasia. The arms and legs are shortened and thickened. The bilateral polydactyly affects the hands and occasionally the feet. Many additional malformations are often present, although cardiac abnormalities are present in only about half of all cases.

Oral Manifestations

A discussion of both the systemic and oral manifestations of the disease has been published by Gorlin and Pindborg, by McKusick and his associates, and by Winter and Geddes.

The most constant oral finding is a fusion of the middle portion of the upper lip to the maxillary gingival margin eliminating the normal mucolateral sulcus. Thus, the middle portion of the upper lip appears hypoplastic.

Natal teeth, prematurely erupted deciduous teeth, frequently occur as well as congenital absence of teeth, particularly in the anterior mandibular segment. Tooth eruption is often delayed and those erupted are commonly defective, being small, cone-shaped, irregularly spaced and demonstrating enamel hypoplasia. Supernumerary teeth are also reported.

Treatment

There is no treatment for the disease. Some patients die in early childhood.

Epidemiology

The overall prevalence of oral lichen planus among Indians was 1.5%; it was highest (3.7%) in those people with mixed oral habits and lowest (0.3%) in nonusers of tobacco. The annual age-adjusted incidence rate was 2.1 and 2.5 per 1,000 among men and women, respectively (Bhonsle et al, 1979). The relative risk for oral lichen planus was highest (13.7) among those who smoked and chewed tobacco.

Etiology

The data available suggests that oral lichen planus is a T-cell-mediated autoimmune disease in which cytotoxic CD8+ T-cells trigger the apoptosis of oral epithelial cells. However, the precise cause of OLP is unknown. The CD8+ lesional T-cells may recognize an antigen associated with the major histocompatibility complex (MHC) class I on keratinocytes. After antigen recognition and activation, CD8+ cytotoxic T-cells may trigger keratinocyte apoptosis. Activated CD8+ T-cells (and possibly keratinocytes) may release cytokines that attract additional lymphocytes into the developing lesion. The lichen planus antigen is unknown, although it may be a selfpeptide. The expression or unmasking of the lichen planus antigen may be induced by drugs (lichenoid drug reaction), contact allergens in dental restorative materials or toothpastes (contact hypersensitivity reaction), mechanical trauma (Koebner phenomenon), viral infection, or unidentified agents. It is interesting to note that the disease is seldom seen in carefree persons; the nervous, high-strung person is almost invariably the one in whom the condition develops. The course of the disease is long, from months to several years, frequently undergoing periods of remission followed by exacerbations which often correspond to periods of emotional upset, overwork, anxiety or some form of mental strain. Other causes suggested include traumatism (since outbreaks often develop along scratch lines), malnutrition and infection.

An interesting association of lichen planus, diabetes mellitus and vascular hypertension has been described by Grinspan, the triad being described as Grinspan’s syndrome by Grupper. However, the reported associations between OLP and systemic diseases may be coincidental, because OLP is relatively common, it occurs predominantly in older adults, and many drugs used in the treatment of systemic diseases trigger the development of oral lichenoid lesions as an adverse effect.

Clinical Features

Oral lichen planus affects all racial groups, with a female-to-male ratio of 1.4:1. It predominantly occurs in adults older than 40 years, although younger adults and children can be affected. The skin lesions of lichen planus appear as small, angular, flat-topped papules only a few millimeter in diameter. These may be discrete or gradually coalesce into larger plaques, each of which is covered by a fine, glistening scale. The papules are sharply demarcated from the surrounding skin. Early in the course of the disease the lesions appear red, but they soon take on a reddish, purple or violaceous hue. Later, a dirty brownish color develops. The center of the papule may be slightly umbilicated. Its surface is covered by characteristic, very fine grayish-white lines, called Wickham’s striae. The lesions may occur anywhere on the skin surface, but usually are distributed in a bilaterally symmetrical pattern, most often on the flexor surfaces of the wrist and forearms, the inner aspect of the knees and thighs, and the trunk, especially the sacral area. The face frequently remains uninvolved. In chronic cases, hypertrophic plaques may develop, especially over the shins. The primary symptom of lichen planus is a severe pruritus that may be intolerable. In patients with OLP, scalp involvement (lichen planopilaris) and nail involvement is rare.

Oral Manifestations

The majority of patients with dermal lichen planus have associated oral lesions of the disease, according to the study of Shklar and McCarthy. Conversely, in a study of 115 patients with oral lichen planus by Andreasen, only 44% had skin lesions as well.

In the oral cavity, the disease assumes a somewhat different clinical appearance than on the skin, and classically is characterized by lesions consisting of radiating white or gray, velvety, thread-like papules in a linear, annular or retiform arrangement forming typical lacy, reticular patches, rings and streaks over the buccal mucosa and to a lesser extent on the lips, tongue and palate. A tiny white elevated dot is frequently present at the intersection of the white lines, known here also as the striae of Wickham. When plaque-like lesions occur, radiating striae may often be seen on their periphery.

Shklar and McCarthy have reported the following distribution of oral lesions: buccal mucosa, 80%; tongue, 65%; lips, 20%; gingiva, floor of mouth and palate, less than 10% (Fig. 19-3). These oral lesions produce no significant symptoms, although occasionally patients will complain of a burning sensation in the involved areas.

Vesicle and bulla formation has been reported in oral lesions of lichen planus, but this is not a common finding, and the diagnosis of lichen planus from the clinical appearance of the lesions is extremely difficult. This bullous form of lichen planus has been discussed by Shklar and Andreasen. Still another type, the so-called erosive form of lichen planus, usually begins as such and not as a progressive process from ‘nonerosive’ lichen planus. Nevertheless the vesicular or bullous form of the disease may clinically resemble erosive lichen planus when the vesicles rupture. Eroded or frankly ulcerated lesions are irregular in size and shape and appear as raw, painful areas in the same general sites involved by the simple or reticular form of the disease (Fig. 19-4). Despite the erosion of the mucosa, the characteristic radiating striae may often be noted on the periphery of the individual lesions.

An atrophic form of lichen planus occurs with some frequency and appears clinically as smooth, red, poorly defined areas, often but not always with peripheral striae evident. The term ‘chronic desquamative gingivitis’ was at one time used to describe a red, diffuse, painful condition of the gingiva, usually found in postmenopausal women and generally quite refractory to therapy. It is now generally accepted that this is not an entity but represents a variety of conditions including the oral manifestations of several dermatologic diseases, one of which is lichen planus (usually the atrophic or erosive form), occurring on the gingiva.

A hypertrophic form of lichen planus may also occur on the oral mucosa, generally appearing as a well-circumscribed, elevated white lesion resembling leukoplakia. In such cases biopsy is usually necessary to establish the diagnosis.

The oral manifestations of lichen planus may occur weeks or months before the appearance of the skin lesions; in fact, in the clinical experience of most investigators, the great majority of patients exhibiting oral lichen planus do not have skin lesions present at the time of presentation of the oral lesions. Indeed, many patients with oral lichen planus never manifest the cutaneous form of the disease, although most patients are not followed up for a sufficiently long time to be absolutely certain of this. Other mucous membranes may be affected also, such as those of the penis, vagina and epiglottis. The genitals are involved in as many as 25% of women with OLP, compared with only 2–4% of men with OLP. Involvement of these locations may occur concomitant with or independent of oral lesions.

A variety of drugs may cause lesions that appear clinically similar to lichen planus and are termed as lichenoid lesions. Oral mucosal lichenoid lesions may occur after the administration of systemic drugs such as nonsteroidal antiinflammatory drugs (NSAIDs), sulfonylureas, antimalarials, beta-blockers, and some angiotensin-converting enzyme (ACE) inhibitors. The period between the commencement of the drug therapy and the clinical appearance of OLP-like disease varies. In rare cases, oral mucosal lichenoid lesions occur after a dental restoration is performed or after the patient starts using a denture; the lag period varies. Patients with an associated allergy to metals or components of the appliance should be evaluated by means of patch testing. In many patients, a cause for the oral lichenoid lesions cannot be identified; in these patients, the disease is called idiopathic OLP. Oral lichenoid reactions are considered to be a part of the spectrum of graft-versus-host disease.

They are present as reticular, erythematous, erosive lesions or ulceration, with whitish streak similar to that of Wickham’s striae of lichen planus. Clinical manifestations of LR are very much similar to that of lichen planus. An important factor which distinguishes LR from lichen planus is its atypical location and absence of bilateral occurrence.

There is no specific test to diagnose LR. The widely accepted criterion is based on the observation of disappearance of the lesions after withdrawal of triggering agent and recurrence of the lesions when it is reintroduced.

Though histologically LR has superficial resemblance to lichen planus there are notable differences. The inflammatory infiltrate is diffuse and extends deeper into the lamina propria unlike the sharp band of infiltrate seen in lichen planus. Inflammatory infiltrate consists of plasma cells and eosinophils in addition to lymphocytes. Increased numbers of colloid or Civatte bodies may be present in LR compared to lichen planus. A perivascular chronic inflammatory cell infiltrate can be seen in drug related lichenoid lesions, which is not commonly found in lichen planus.

Proliferative verrucous leukoplakia, an unusual form of leukoplakia shares some demographic and clinical similarities with lichen planus. It occurs most commonly in older female patients and is not associated with tobacco usage. Microscopically it exhibits epithelial dysplasia with a band-like inflammatory infiltrate which on low-power can mimic lichen planus and is known as lichenoid dysplasia.

Identification and elimination of the triggering factors play a major role in the management of LR. Lichenoid lesions can take many months or longer to resolve. The malignant transformation rate is reportedly higher in oral lichenoid lesions which do not have all the typical clinical and histologic features of oral lichen planus.

Histologic Findings

Histopathologic examination of lesional tissue is the most relevant investigation in cases of OLP. Typical findings include hyperparakeratosis or hyperorthokeratosis with thickening of the granular layer, acanthosis with intracellular edema of the spinous cells in some instances, the development of a ‘saw tooth’ appearance of the rete pegs. Band-like subepithelial mononuclear infiltrate consisting of T-cells and histiocytes; increased numbers of intraepithelial T-cells; and degenerating basal keratinocytes that form colloid (Civatte, hyaline, cytoid) bodies, which appear as homogenous eosinophilic globules are consistently seen.

Degeneration of the basal keratinocytes and disruption of the anchoring elements of the epithelial basement membrane and basal keratinocytes (e.g. hemidesmosomes, filaments, fibrils) weakens the epithelial-connective tissue interface. As a result, histologic clefts (i.e. Max-Joseph spaces) may form, and blisters on the oral mucosa (bullous lichen planus) may be seen at clinical examination. B cells and plasma cells are uncommon findings (Fig. 19-5).

Immunoglobulin or complement deposits are not a consistent feature of OLP. In some instances, fibrinogen and fibrin are deposited in a linear pattern in the basement membrane zone. Colloid bodies contain fibrin, IgM, C3, C4, and keratin. Laminin and fibronectin staining may be absent in areas of heavy fibrin deposition and colloid body formation; this finding suggests basement membrane damage in these areas. Direct immunofluorescent studies of lichen planus by Daniels and Quadra-White have shown that nearly all specimens from oral lesions of this disease react with antifibrinogen and exhibit an intensely positive fluorescence that outlines the basement membrane zone with numerous irregular extensions into the superficial lamina propria. This particular pattern is characteristic of both lichen planus and lupus erythematosus. This is not present in pemphigoid or erythema multiforme, in both of which the fluorescence instead tends to form a patchy linear pattern, nor is it seen in pemphigus, in which the fluorescence has a granular pattern. These workers reported a general absence of immunoglobulins in lichen planus lesions while only a few specimens exhibited a fine granular fluorescence with anti-C3 (complement) at the basement membrane zone. They concluded that the pattern of fibrinogen deposition, in the absence of fluorescence by other reagents, is sufficiently unique to be used as a diagnostic criterion for oral mucosal lichen planus.

In OLP, electron microscopy is used principally as a research tool. The ultrastructure of the colloid bodies suggests that they are apoptotic keratinocytes, and recent studies of the endlabeling method revealed DNA fragmentation in these cells. Electron microscopy shows breaks, branches, and duplications of the basement membrane in OLP.

Differential Diagnosis

It is important that lichen planus be differentiated from other lesions of the oral cavity which may present a similar clinical appearance, but which may have a different prognosis. Oral lesions which bear superficial resemblance to lichen planus include lichenoid reactions, leukoplakia, candidiasis, pemphigus, cicatricial pemphigoid, erythema multiforme, syphilis, recurrent aphthae and lupus erythematosus (q.v.). Although microscopic examination of tissue may be necessary to establish a definitive diagnosis, the clinical characteristics of these various diseases are often sufficient to differentiate one from the other.

Malignant Transformation

There is some controversy regarding its malignant potential. There seems to be a slightly higher incidence of oral squamous cell carcinoma in patients with oral lichen planus than in the general population. The actual overall frequency of malignant transformation is low, varying between 0.3 and 3%. The forms that more commonly undergo malignant transformation are the erosive and atrophic forms.

Treatment

At present there is no cure, although various agents have been tried. Due to its minimal potential for malignant transformation, these patients used to be kept on longterm follow-up. Medical treatment of OLP is essential for the management of painful, erythematous, erosive, or bullous lesions. The principal aims of current OLP therapy are the resolution of painful symptoms, the resolution of oral mucosal lesions, the reduction of the risk of oral cancer, and the maintenance of good oral hygiene. As it is an autoimmune mediated condition, corticosteroids are recommended. In patients with recurrent painful disease, another goal is the prolongation of their symptom free intervals. The main concerns with the current therapies are the local and systemic adverse effects and lesion recurrence after treatment is withdrawn. Patients should be observed periodically, particularly those with the erosive or atrophic forms and those who also have a history of alcohol and tobacco misuse, because of the risk of malignant transformation.

Etiology

The cause of psoriasis is unknown. Patients do have a genetic predisposition for the disease; the disease has a strong association with HLA Cw6 and B57 region. Recent evidence suggests that in addition to these regions many other gene loci such as 19p13, 17q25, and 1q21 may also increase the susceptibility to this disease. The trigger event may be unknown in most cases but is likely to be an immunologic event. Significant evidence is accumulating that psoriasis is an autoimmune disease. Lesions of psoriasis are associated with increased activity of T-cells in underlying skin. Also of significance is that 2.5% of persons with HIV develop psoriasis during the course of the disease. Perceived stress can cause exacerbation of psoriasis. Some authors suggest that psoriasis is a stress-related disease and offer findings of increased concentrations of neurotransmitters in psoriatic plaques. The pathogenesis of psoriatic lesions is due to an increase in the turnover rate of dermal cells, from the normal turnover duration of 23 days to three to five days in affected areas (Fig. 19-6). As would be expected, there is also a dramatic increase in the mitotic index of psoriatic skin which is said to even surpass that of epidermoid carcinoma.

Clinical Features

Psoriasis of the skin is characterized by the occurrence of small, sharply delineated, dry papules, each covered by a delicate silvery scale which has been described as resembling a thin layer of mica. If the deep scales are removed, one or more tiny bleeding points are disclosed, a characteristic feature termed Auspitz’s sign. After removal of the scale the surface of the skin is red and dusky in appearance.

The cutaneous lesions, which are painless and seldom pruritic, may be few in number or extensive in distribution. The papules enlarge at the periphery and tend to become slightly infiltrating and elevated, smaller lesions coalescing to form large plaques of irregular outline. They are roughly symmetrical and are most frequently grouped on the extensor surfaces of the extremities, particularly the elbows and knees, the scalp, back and chest, face and abdomen. Involvement of the hands and feet, with the exception of the fingernail, is uncommon.

The disease commences with the appearance of a few small papules, which gradually increase in size. New lesions slowly arise over a period of weeks, months or even years. The disease may remain static for a long time, progresses slowly to involve more and more skin area, or exhibits acute generalized exacerbations. The disease is more severe in the winter and less severe in the summer as a result of increased exposure to ultraviolet light; patients who move to a warm sunny climate usually undergo improvement in their condition. Mental anxiety or stress almost invariably appears to increase the severity of the disease or induce acute exacerbations. Arthritis is a complication in about 12% of persons with psoriasis, according to Allen. Psoriasis is uncommon in children, and seldom does a primary attack occur after the age of 45 years; it most frequently arises in the second and third decades of life. The median age at onset is 28 years. Psoriasis is slightly more common in women.

Oral Manifestations

Most authorities consider psoriatic involvement of oral mucosa extremely rare and point out that many oral lesions occurring concomitant with psoriasis of the skin are actually other diseases such as leukoplakia or lichen planus. In fact some investigators deny the existence of oral psoriasis. For example, in a study of 100 patients with dermal psoriasis, Buchner and Begleiter found none with oral lesions of the disease. However, they did note in these patients an 11% incidence of angular cheilosis, 6% incidence of fissured tongue and 5% incidence of benign migratory glossitis. Nevertheless it has been reported that in occasional cases oral lesions have exhibited all histologic features of psoriasis and in some instances have been identical with the coexisting skin lesions.

Such lesions have been reported on the lips, buccal mucosa, palate, gingiva and floor of the mouth (Fig. 19-7). Clinically, they are described as gray or yellowish-white plaques; as silvery white, scaly lesions with an erythematous base; as multiple papular eruptions which may be ulcerated; or as small, papillary, elevated lesions with a scaly surface. Reports by Goldman and Bloom and by Levin emphasized the vagaries in the clinical appearance of oral psoriasis. Psoriasis of the gingiva was reported by Brayshaw and Orban and that of the alveolar ridge by Wooten and his associates in patients without skin lesions; however, cases of mucosal involvement without skin manifestations must be viewed with caution even though the histologic sections of the lesions do present a psoriasiform pattern. White and his associates have reviewed the literature on intraoral psoriasis while reporting an additional case. Fischman and his coworkers studied an oral lesion in a patient with skin lesions of psoriasis utilizing light and electron microscopy, as well as immunologic methods, and noted in all instances that the findings in the oral lesion were similar to those in the skin lesions. They concluded that true oral lesions do occur in psoriasis.

The general problem of ‘psoriasiform’ lesions of the oral mucosa has been reviewed by Weathers and his associates. These lesions included psoriasis, Reiter’s syndrome, benign migratory glossitis and ‘ectopic geographic tongue’, and the authors concluded that their exact interrelationship, if any, is still unknown.

Histologic Features

The microscopic appearance of psoriasis is characterized by uniform parakeratosis, absence of the stratum granulosum and elongation and clubbing of the rete pegs (Figs. 19-8, 19-9). The epithelium over the connective tissue papillae is thinned, and it is from these points that bleeding occurs when the scales are peeled off. Tortuous, dilated capillaries extending high in the papillae are prominent. Intraepithelial microabscesses (Monro’s abscesses) are a common but not invariable finding; they are reported by Pisanty and Ship to be absent in oral psoriasis (Fig. 19-10). Mild lymphocytic and histiocytic infiltration of the connective tissue is also typical, particularly perivascular and periadnexal in location.

Treatment

The lesions are usually benign but a few cases may be refractory to treatment. Treatments for more general or advanced psoriasis include UV-A light, psoralen plus UV-A light (PUVA), retinoids (e.g., isotretinoin, acitretin), methotrexate (particularly for arthritis), cyclosporine, and alefacept.

Etiology

Pityriasis rosea has often been considered to be a viral exanthem. Its clinical presentation supports this concept. It has an increased incidence in individuals who are immunocompromised. As with viral exanthems, a single outbreak tends to elicit lifelong immunity. Despite these tendencies, no single virus has been proven to cause the disease. A number of viruses have been studied for a link to PR, which include picornavirus and parvovirus B19. Other recent work demonstrated human herpesvirus 7 (HHV-7) viral DNA in the lesions and the plasma of patients with PR. However, because HHV-7 is frequently found in healthy individuals, its etiologic role is controversial. Lesions are also thought to be increased in individuals with high stress levels.

Clinical Features

The disease is more common in hot, dry climate countries like Australia, Malaysia and India. PR is more common in women than in men and commonly develops in children and young adults, although any age group can be affected. Pityriasis rosea is characterized by the appearance of superficial light red macules or papules, either generalized over most of the skin surface, with the usual exception of the face and hands, or localized to certain areas such as the trunk, thighs, axillae or groin. This generalized outbreak is frequently preceded by the appearance of a ‘primary lesion’ or ‘herald spot’ 7–10 days previously. This spot is brighter red and larger (3–4 cm in diameter) than the multiple eruptions which follow its appearance. The individual exanthematous lesions are commonly ovoid, with the long axis parallel to the natural lines of cleavage of the skin, and are covered by a thin silvery scale.

The lesions often manifest mild itching sometimes accompanied by headache and low-grade fever; cervical lymphadenopathy may also be present.

Pityriasis rosea usually runs its course in three to six weeks and seldom recurs. It is interesting that the disease occurs seasonally, being far more common in the spring and autumn than at other times.

Oral Manifestations

It was pointed out by Guequierre and Wright, and confirmed by others, that involvement of the oral mucous membranes occurs with some frequency in pityriasis rosea. The oral lesions appear either concomitantly with or subsequent to the skin manifestations; they are not present throughout the clinical course of the disease, but are usually prominent during its most severe phase.

The oral lesions usually occur only on the buccal mucosa, although both tongue and palatal lesions have also been recorded. They appear as erythematous macules with or without a central area of grayish desquamation. The lesions may be single or multiple, are irregular in shape, occasionally show a raised border and vary in size from a few millimeters to 1 or 2 cm in diameter. These lesions are asymptomatic and of no clinical significance. They clear simultaneously with the skin lesions.

Histologic Features

The microscopic changes in pityriasis rosea are not pathognomonic, but consist of slight acanthosis and focal parakeratosis with microvesiculation or simply sprinkling of leukocytes within the epithelium. In addition, edema, hyperemia and perivascular infiltration of lymphocytes, plasma cells and histiocytes are prominent in the superficial connective tissue. Increased amounts of CD4 T-cells and Langhans cells are present in the dermis; this observation may indicate viral antigen processing and presentation. The histologic features suggest little more than a nonspecific dermatitis.

Treatment

The most important part of treating patients with PR is reassurance that the rash will resolve. Relief of pruritus is helpful and can be accomplished by using topical steroids, oral antihistamines, topical menthol-phenol lotions, and oatmeal baths. Systemic steroids are not recommended. Although they suppress pruritus, systemic steroids do not shorten the overall disease; in fact, they may prolong or exacerbate the disease. Ultraviolet B (UV-B) light therapy may rapidly relieve pruritus in resistant cases. One must take into consideration the possibility of postinflammatory pigmentation with light therapy. The prognosis for PR is excellent. Patients may return to work or school because they are not considered to be contagious.

Etiology

Many suspected etiologic factors have been reported to cause EM. EM and SJS are both caused by drugs, but infectious agents are considered to be the major cause of EM. Today, EM minor is regarded as being triggered by HSV in nearly 100% of cases; many instances of idiopathic EM minor may be precipitated by subclinical HSV infection. A herpetic etiology also accounts for 55% of cases of EM major. Among the other infections, Mycoplasma infection appears to be a common cause. Drugs are reported in many documented cases of SJS and EM major. Sulfa drugs are the most common triggers.

Clinical Features

Erythema multiforme occurs chiefly in young adults, although it may develop at any age, the highest incidence is in the second to fourth decades of life and affects males more frequently than females. This disease is characterized by the occurrence of asymptomatic, vividly erythematous discrete macules, papules or occasionally vesicles and bullae distributed in a rather symmetrical pattern most commonly over the hands and arms, feet and legs, face and neck. The individual lesions may vary considerably in size even in the same patient, but are generally only a few centimeters or less in diameter. A concentric ringlike appearance of the lesions, resulting from the varying shades of erythema, occurs in some cases and has given rise to the terms ‘target’, ‘iris’, or ‘bull’s eye’ in describing them (Fig. 19-11). They are most common on the hands, wrists and ankles. Mucous membrane involvement, including the oral cavity, is common. The lesions make their appearance rapidly, usually within a day or two, and persist from several days to a few weeks, gradually fading and eventually clearing. Recurrence of the disease over a period of years is common, however.