Contact Dermatitis

Psoriasiform dermatitis seen with Bazex syndrome may involve the nose and the helices of the ears in addition to the palms and soles. In most reported cases, the appearance of the characteristic psoriasiform lesions preceded the diagnosis of the associated underlying malignancy. Skin scrapings for potassium hydroxide and fungal cultures should be performed, and skin biopsy of keratotic plaques is recommended to exclude psoriasis.

Case Report

A 70-year-old man with no personal or family history of psoriasis or other skin diseases developed psoriasiform dermatitis of the fingers, toes, and helices of the ears over a period of 3 months. He reported a history of cigarette smoking (1 pack per day) with significant consumption of alcoholic beverages over a period of 30 years. Results from a review of systems revealed progressive hoarseness and dysphagia, with a recent history of a 15-lb weight loss. On physical examination, psoriasiform plaques were seen on the palms and soles, as well as on the helices of the ears (Figure 1) and the tip and dorsum of the nose. There was a yellowish discoloration and dystrophy of all the fingernails and toenails (Figure 2). Results from potassium hydroxide preparations from scrapings of the palms and soles were negative, and fungal culture did not grow any pathogenic fungi.

Six weeks later, the patient developed bilateral cervical lymphadenopathy. Otolaryngologic examination consisted of direct laryngoscopy; imaging studies including magnetic resonance imaging and computed tomography scans; and laryngeal biopsy, which revealed a stage IV squamous cell carcinoma (SCC) confined to the head and neck area. Although the patient did not return for follow-up, management of the laryngeal SCC with surgery and postoperative chemotherapy completely cleared his skin and nail lesions without adjunct dermatologic treatments.

PLEASE REFER TO THE PDF TO VIEW THE FIGURES

Comment

Bazex syndrome (paraneoplastic acrokeratosis) was first described as a clinical entity by Gougerot and Rupp¹ more than 40 years prior to the coining of the disease's current widely used eponym of Bazex syndrome. In 1922, Gougerot and Grupper¹ described a patient with hyperkeratotic lesions on the nose, ears, palms, and soles in conjunction with an SCC on the tongue. Years later, Bazex and colleagues² described a patient with an SCC of the pyriform fossa and an associated psoriasiform dermatosis. Since that report, more than 110 cases of Bazex syndrome have been reported, most of which describe the condition as a cutaneous paraneoplastic syndrome characterized by psoriasiform lesions associated with an underlying malignancy of the upper aerodigestive tract (oropharynx, larynx, or esophagus), most often of the SCC subtype.^3-7

Bazex syndrome can be classified among the cutaneous paraneoplastic disorders that also include acanthosis nigricans maligna, erythema gyratum, necrolytic migratory erythema, and hypertrichosis lanuginosa acquisita.⁷ The cutaneous manifestations of Bazex syndrome are paraneoplastic in that the developing skin changes coevolve with an underlying malignancy; these cutaneous hallmarks of the syndrome do not, however, represent metastatic extensions of this malignancy. On the contrary, they may actually serve as harbingers of future oncologic progression.

The cutaneous changes observed in Bazex syndrome have been classified into 3 stages.³ In the first stage, psoriasiform changes of the fingers, toes, auricular helix, and nose are noted. In addition, the earliest stage of the syndrome is characterized by nail changes, including horizontal and vertical ridging, subungual hyperkeratosis, yellow discoloration, and nail dystrophy. During this stage, the primary tumor is considered asymptomatic. The second stage is primarily typified by proximal extension of the cutaneous changes observed in the first stage to involve the dorsum of the hands and feet, as well as the malar regions of the face. Local symptoms secondary to growth of the primary tumor also may surface during this stage. The third stage in the course of the syndrome is defined by progressive centripetal extension of the cutaneous disease process to affect regions of the arms and legs (nails, hands, elbows, knees, and feet), scalp, and trunk.^3-7 Other cutaneous changes that have been reported include hyperpigmentation, particularly in individuals with darker skin pigmentation,6 and development of bullous lesions.^5,8,9

Based on the initial dermatologic manifestations of Bazex syndrome, it is not surprising that the condition is often misdiagnosed as psoriasis or chronic dermatitis. Indeed, histopathologic examination of skin lesions in the syndrome is nonspecific and may mimic psoriasis or other more common dermatoses, demonstrating hyperkeratosis, parakeratosis, acanthosis, vacuolar degeneration of keratinocytes, and/or perivascular lymphohistiocytic infiltrate.^6,7,10 One potential distinguishing feature of Bazex syndrome, however, is specific psoriasiform involvement of the helix of the ear, as opposed to the entire ear, as would be more commonly expected in psoriasis.⁷ The tip of the nose also is involved in Bazex syndrome, which is an unusual location for psoriasis.

Extensive reviews of the literature reporting cases of Bazex syndrome demonstrate that most patients have been Caucasian, male, of French descent, and older than 40 years.^6,7 SCCs have accounted for nearly 60% of tumors found in patients with this syndrome, and adenocarcinomas have accounted for less than 10% of malignancies. Furthermore, the majority of the neoplasms have involved the oropharynx and larynx.⁷ These neoplasms may be silent and only present with lymph node metastases. Less commonly, primary tumors may occur in the lungs and esophagus. Rare cases of neoplasms of the prostate, liver, stomach, thymus, uterus, vulva, and lymphoid tissues also have been reported.¹¹ Numerous cases have been described in which the primary tumor could not be identified, and affected patients were diagnosed on the basis of metastases to cervical lymph nodes. In the vast majority of reported cases, the appearance of the characteristic psoriasiform lesions preceded the diagnosis of the associated malignancy.^6,7 Finally, the skin lesions either markedly improved or completely resolved in the great preponderance of patients in whom the underlying malignancy was either treated with chemotherapy and/or radiation therapy or surgical excision.^6,7,10-12 This was true of the patient presented in this report.

The pathogenesis of Bazex syndrome remains a mystery, though several authors have suggested an autoimmune etiology based on the common histologic finding of inflammatory infiltrates along the basal cell layer of affected skin regions.^5,8,9 The immune reaction may be humoral or cellular; the proposed mechanism states that cross reactivity between skin and tumor antigens may produce the characteristic cutaneous changes observed, because antitumor antibodies cross reacting with the epidermis or basement membrane zone could elicit an immunologic response resulting in basal cell layer damage.^13,14 Several authors also have proposed that the tumors may produce a host of growth factors that collectively lead to hyperkeratotic skin changes.^14,15

Ideal treatment of Bazex syndrome is eradication of the underlying malignancy. Unresectable or treatment-resistant tumors, however, pose a significant challenge for the clinician. Numerous studies have been conducted demonstrating equivocal efficacies of various standard dermatological therapies in the treatment of skin lesions occurring in this syndrome. Unfortunately, in the vast majority of patients, such treatment options as topical tar, topical and systemic corticosteroids, UVB irradiation, antifungals, and antibiotics have proven to be of little use.6,7 Gill and colleagues9 have reported that oral psoralen–UVA phototherapy may offer some promise of effective treatment in these patients. However, larger studies are required to further investigate the therapeutic benefits of this treatment option. Although the management of treatment-resistant cutaneous lesions in Bazex syndrome may prove problematic, it is clear that the clinician must be astute in recognizing this disease process in its earlier stages to identify and effectively treat any underlying malignancy as expeditiously as possible.

Acknowledgment—The authors wish to thank Dr. Eric Ehrsam for his assistance with the preparation of this manuscript.

Psoriasiform dermatitis seen with Bazex syndrome may involve the nose and the helices of the ears in addition to the palms and soles. In most reported cases, the appearance of the characteristic psoriasiform lesions preceded the diagnosis of the associated underlying malignancy. Skin scrapings for potassium hydroxide and fungal cultures should be performed, and skin biopsy of keratotic plaques is recommended to exclude psoriasis.

Case Report

A 70-year-old man with no personal or family history of psoriasis or other skin diseases developed psoriasiform dermatitis of the fingers, toes, and helices of the ears over a period of 3 months. He reported a history of cigarette smoking (1 pack per day) with significant consumption of alcoholic beverages over a period of 30 years. Results from a review of systems revealed progressive hoarseness and dysphagia, with a recent history of a 15-lb weight loss. On physical examination, psoriasiform plaques were seen on the palms and soles, as well as on the helices of the ears (Figure 1) and the tip and dorsum of the nose. There was a yellowish discoloration and dystrophy of all the fingernails and toenails (Figure 2). Results from potassium hydroxide preparations from scrapings of the palms and soles were negative, and fungal culture did not grow any pathogenic fungi.

Six weeks later, the patient developed bilateral cervical lymphadenopathy. Otolaryngologic examination consisted of direct laryngoscopy; imaging studies including magnetic resonance imaging and computed tomography scans; and laryngeal biopsy, which revealed a stage IV squamous cell carcinoma (SCC) confined to the head and neck area. Although the patient did not return for follow-up, management of the laryngeal SCC with surgery and postoperative chemotherapy completely cleared his skin and nail lesions without adjunct dermatologic treatments.

PLEASE REFER TO THE PDF TO VIEW THE FIGURES

Comment

Bazex syndrome (paraneoplastic acrokeratosis) was first described as a clinical entity by Gougerot and Rupp¹ more than 40 years prior to the coining of the disease's current widely used eponym of Bazex syndrome. In 1922, Gougerot and Grupper¹ described a patient with hyperkeratotic lesions on the nose, ears, palms, and soles in conjunction with an SCC on the tongue. Years later, Bazex and colleagues² described a patient with an SCC of the pyriform fossa and an associated psoriasiform dermatosis. Since that report, more than 110 cases of Bazex syndrome have been reported, most of which describe the condition as a cutaneous paraneoplastic syndrome characterized by psoriasiform lesions associated with an underlying malignancy of the upper aerodigestive tract (oropharynx, larynx, or esophagus), most often of the SCC subtype.^3-7

Bazex syndrome can be classified among the cutaneous paraneoplastic disorders that also include acanthosis nigricans maligna, erythema gyratum, necrolytic migratory erythema, and hypertrichosis lanuginosa acquisita.⁷ The cutaneous manifestations of Bazex syndrome are paraneoplastic in that the developing skin changes coevolve with an underlying malignancy; these cutaneous hallmarks of the syndrome do not, however, represent metastatic extensions of this malignancy. On the contrary, they may actually serve as harbingers of future oncologic progression.

The cutaneous changes observed in Bazex syndrome have been classified into 3 stages.³ In the first stage, psoriasiform changes of the fingers, toes, auricular helix, and nose are noted. In addition, the earliest stage of the syndrome is characterized by nail changes, including horizontal and vertical ridging, subungual hyperkeratosis, yellow discoloration, and nail dystrophy. During this stage, the primary tumor is considered asymptomatic. The second stage is primarily typified by proximal extension of the cutaneous changes observed in the first stage to involve the dorsum of the hands and feet, as well as the malar regions of the face. Local symptoms secondary to growth of the primary tumor also may surface during this stage. The third stage in the course of the syndrome is defined by progressive centripetal extension of the cutaneous disease process to affect regions of the arms and legs (nails, hands, elbows, knees, and feet), scalp, and trunk.^3-7 Other cutaneous changes that have been reported include hyperpigmentation, particularly in individuals with darker skin pigmentation,6 and development of bullous lesions.^5,8,9

Based on the initial dermatologic manifestations of Bazex syndrome, it is not surprising that the condition is often misdiagnosed as psoriasis or chronic dermatitis. Indeed, histopathologic examination of skin lesions in the syndrome is nonspecific and may mimic psoriasis or other more common dermatoses, demonstrating hyperkeratosis, parakeratosis, acanthosis, vacuolar degeneration of keratinocytes, and/or perivascular lymphohistiocytic infiltrate.^6,7,10 One potential distinguishing feature of Bazex syndrome, however, is specific psoriasiform involvement of the helix of the ear, as opposed to the entire ear, as would be more commonly expected in psoriasis.⁷ The tip of the nose also is involved in Bazex syndrome, which is an unusual location for psoriasis.

Extensive reviews of the literature reporting cases of Bazex syndrome demonstrate that most patients have been Caucasian, male, of French descent, and older than 40 years.^6,7 SCCs have accounted for nearly 60% of tumors found in patients with this syndrome, and adenocarcinomas have accounted for less than 10% of malignancies. Furthermore, the majority of the neoplasms have involved the oropharynx and larynx.⁷ These neoplasms may be silent and only present with lymph node metastases. Less commonly, primary tumors may occur in the lungs and esophagus. Rare cases of neoplasms of the prostate, liver, stomach, thymus, uterus, vulva, and lymphoid tissues also have been reported.¹¹ Numerous cases have been described in which the primary tumor could not be identified, and affected patients were diagnosed on the basis of metastases to cervical lymph nodes. In the vast majority of reported cases, the appearance of the characteristic psoriasiform lesions preceded the diagnosis of the associated malignancy.^6,7 Finally, the skin lesions either markedly improved or completely resolved in the great preponderance of patients in whom the underlying malignancy was either treated with chemotherapy and/or radiation therapy or surgical excision.^6,7,10-12 This was true of the patient presented in this report.

The pathogenesis of Bazex syndrome remains a mystery, though several authors have suggested an autoimmune etiology based on the common histologic finding of inflammatory infiltrates along the basal cell layer of affected skin regions.^5,8,9 The immune reaction may be humoral or cellular; the proposed mechanism states that cross reactivity between skin and tumor antigens may produce the characteristic cutaneous changes observed, because antitumor antibodies cross reacting with the epidermis or basement membrane zone could elicit an immunologic response resulting in basal cell layer damage.^13,14 Several authors also have proposed that the tumors may produce a host of growth factors that collectively lead to hyperkeratotic skin changes.^14,15

Ideal treatment of Bazex syndrome is eradication of the underlying malignancy. Unresectable or treatment-resistant tumors, however, pose a significant challenge for the clinician. Numerous studies have been conducted demonstrating equivocal efficacies of various standard dermatological therapies in the treatment of skin lesions occurring in this syndrome. Unfortunately, in the vast majority of patients, such treatment options as topical tar, topical and systemic corticosteroids, UVB irradiation, antifungals, and antibiotics have proven to be of little use.6,7 Gill and colleagues9 have reported that oral psoralen–UVA phototherapy may offer some promise of effective treatment in these patients. However, larger studies are required to further investigate the therapeutic benefits of this treatment option. Although the management of treatment-resistant cutaneous lesions in Bazex syndrome may prove problematic, it is clear that the clinician must be astute in recognizing this disease process in its earlier stages to identify and effectively treat any underlying malignancy as expeditiously as possible.

Acknowledgment—The authors wish to thank Dr. Eric Ehrsam for his assistance with the preparation of this manuscript.

Psoriasiform dermatitis seen with Bazex syndrome may involve the nose and the helices of the ears in addition to the palms and soles. In most reported cases, the appearance of the characteristic psoriasiform lesions preceded the diagnosis of the associated underlying malignancy. Skin scrapings for potassium hydroxide and fungal cultures should be performed, and skin biopsy of keratotic plaques is recommended to exclude psoriasis.

Case Report

A 70-year-old man with no personal or family history of psoriasis or other skin diseases developed psoriasiform dermatitis of the fingers, toes, and helices of the ears over a period of 3 months. He reported a history of cigarette smoking (1 pack per day) with significant consumption of alcoholic beverages over a period of 30 years. Results from a review of systems revealed progressive hoarseness and dysphagia, with a recent history of a 15-lb weight loss. On physical examination, psoriasiform plaques were seen on the palms and soles, as well as on the helices of the ears (Figure 1) and the tip and dorsum of the nose. There was a yellowish discoloration and dystrophy of all the fingernails and toenails (Figure 2). Results from potassium hydroxide preparations from scrapings of the palms and soles were negative, and fungal culture did not grow any pathogenic fungi.

Six weeks later, the patient developed bilateral cervical lymphadenopathy. Otolaryngologic examination consisted of direct laryngoscopy; imaging studies including magnetic resonance imaging and computed tomography scans; and laryngeal biopsy, which revealed a stage IV squamous cell carcinoma (SCC) confined to the head and neck area. Although the patient did not return for follow-up, management of the laryngeal SCC with surgery and postoperative chemotherapy completely cleared his skin and nail lesions without adjunct dermatologic treatments.

PLEASE REFER TO THE PDF TO VIEW THE FIGURES

Comment

Bazex syndrome (paraneoplastic acrokeratosis) was first described as a clinical entity by Gougerot and Rupp¹ more than 40 years prior to the coining of the disease's current widely used eponym of Bazex syndrome. In 1922, Gougerot and Grupper¹ described a patient with hyperkeratotic lesions on the nose, ears, palms, and soles in conjunction with an SCC on the tongue. Years later, Bazex and colleagues² described a patient with an SCC of the pyriform fossa and an associated psoriasiform dermatosis. Since that report, more than 110 cases of Bazex syndrome have been reported, most of which describe the condition as a cutaneous paraneoplastic syndrome characterized by psoriasiform lesions associated with an underlying malignancy of the upper aerodigestive tract (oropharynx, larynx, or esophagus), most often of the SCC subtype.^3-7

Bazex syndrome can be classified among the cutaneous paraneoplastic disorders that also include acanthosis nigricans maligna, erythema gyratum, necrolytic migratory erythema, and hypertrichosis lanuginosa acquisita.⁷ The cutaneous manifestations of Bazex syndrome are paraneoplastic in that the developing skin changes coevolve with an underlying malignancy; these cutaneous hallmarks of the syndrome do not, however, represent metastatic extensions of this malignancy. On the contrary, they may actually serve as harbingers of future oncologic progression.

The cutaneous changes observed in Bazex syndrome have been classified into 3 stages.³ In the first stage, psoriasiform changes of the fingers, toes, auricular helix, and nose are noted. In addition, the earliest stage of the syndrome is characterized by nail changes, including horizontal and vertical ridging, subungual hyperkeratosis, yellow discoloration, and nail dystrophy. During this stage, the primary tumor is considered asymptomatic. The second stage is primarily typified by proximal extension of the cutaneous changes observed in the first stage to involve the dorsum of the hands and feet, as well as the malar regions of the face. Local symptoms secondary to growth of the primary tumor also may surface during this stage. The third stage in the course of the syndrome is defined by progressive centripetal extension of the cutaneous disease process to affect regions of the arms and legs (nails, hands, elbows, knees, and feet), scalp, and trunk.^3-7 Other cutaneous changes that have been reported include hyperpigmentation, particularly in individuals with darker skin pigmentation,6 and development of bullous lesions.^5,8,9

Based on the initial dermatologic manifestations of Bazex syndrome, it is not surprising that the condition is often misdiagnosed as psoriasis or chronic dermatitis. Indeed, histopathologic examination of skin lesions in the syndrome is nonspecific and may mimic psoriasis or other more common dermatoses, demonstrating hyperkeratosis, parakeratosis, acanthosis, vacuolar degeneration of keratinocytes, and/or perivascular lymphohistiocytic infiltrate.^6,7,10 One potential distinguishing feature of Bazex syndrome, however, is specific psoriasiform involvement of the helix of the ear, as opposed to the entire ear, as would be more commonly expected in psoriasis.⁷ The tip of the nose also is involved in Bazex syndrome, which is an unusual location for psoriasis.

Extensive reviews of the literature reporting cases of Bazex syndrome demonstrate that most patients have been Caucasian, male, of French descent, and older than 40 years.^6,7 SCCs have accounted for nearly 60% of tumors found in patients with this syndrome, and adenocarcinomas have accounted for less than 10% of malignancies. Furthermore, the majority of the neoplasms have involved the oropharynx and larynx.⁷ These neoplasms may be silent and only present with lymph node metastases. Less commonly, primary tumors may occur in the lungs and esophagus. Rare cases of neoplasms of the prostate, liver, stomach, thymus, uterus, vulva, and lymphoid tissues also have been reported.¹¹ Numerous cases have been described in which the primary tumor could not be identified, and affected patients were diagnosed on the basis of metastases to cervical lymph nodes. In the vast majority of reported cases, the appearance of the characteristic psoriasiform lesions preceded the diagnosis of the associated malignancy.^6,7 Finally, the skin lesions either markedly improved or completely resolved in the great preponderance of patients in whom the underlying malignancy was either treated with chemotherapy and/or radiation therapy or surgical excision.^6,7,10-12 This was true of the patient presented in this report.

The pathogenesis of Bazex syndrome remains a mystery, though several authors have suggested an autoimmune etiology based on the common histologic finding of inflammatory infiltrates along the basal cell layer of affected skin regions.^5,8,9 The immune reaction may be humoral or cellular; the proposed mechanism states that cross reactivity between skin and tumor antigens may produce the characteristic cutaneous changes observed, because antitumor antibodies cross reacting with the epidermis or basement membrane zone could elicit an immunologic response resulting in basal cell layer damage.^13,14 Several authors also have proposed that the tumors may produce a host of growth factors that collectively lead to hyperkeratotic skin changes.^14,15

Ideal treatment of Bazex syndrome is eradication of the underlying malignancy. Unresectable or treatment-resistant tumors, however, pose a significant challenge for the clinician. Numerous studies have been conducted demonstrating equivocal efficacies of various standard dermatological therapies in the treatment of skin lesions occurring in this syndrome. Unfortunately, in the vast majority of patients, such treatment options as topical tar, topical and systemic corticosteroids, UVB irradiation, antifungals, and antibiotics have proven to be of little use.6,7 Gill and colleagues9 have reported that oral psoralen–UVA phototherapy may offer some promise of effective treatment in these patients. However, larger studies are required to further investigate the therapeutic benefits of this treatment option. Although the management of treatment-resistant cutaneous lesions in Bazex syndrome may prove problematic, it is clear that the clinician must be astute in recognizing this disease process in its earlier stages to identify and effectively treat any underlying malignancy as expeditiously as possible.

Acknowledgment—The authors wish to thank Dr. Eric Ehrsam for his assistance with the preparation of this manuscript.

Case Report

A healthy 12-year-old African American boy presented with a 3-month history of an asymptomatic, papular, perioral eruption. He had been previously treated by a primary care provider, who had prescribed a low-potency and then a medium-potency topical corticosteroid, without improvement. The patient's parents denied that he had used topical corticosteroids or other topical preparations prior to the eruption. He took no oral medications, and the findings of the review of systems were within reference range. Results of a physical examination revealed numerous, discrete and coalescing, firm, pink, hyperpigmented papules ranging from 2 to 4 mm in diameter, primarily located in the perioral area (Figure). A few papules were noted around the nose and eyes. Results of a shave biopsy of a perioral papule revealed dermal granulomatous inflammation. The infiltrate consisted of histiocytes and lymphocytes and also included several focal collections of neutrophils. There was overlying parakeratosis. Results of a periodic acid–Schiff, Gomori methenamine-silver, Brown-Brenn, and Fite-Farraco stains were negative for organisms.

The patient was diagnosed with granulomatous periorificial dermatitis (GPD), and treatment with oral tetracycline 500 mg twice a day was initiated. Six days later, a tapering course of oral prednisone was added (consisting of 40 mg for 3 days, 30 mg for 3 days, 20 mg for 3 days, and 10 mg for 3 days) because of the severe extent of the eruption and the social distress it was causing the patient. Within 3 weeks, a dramatic decrease in the eruption was noted, with only a few small papules remaining. The patient was then switched from oral tetracycline to topical clindamycin twice a day for maintenance, but he did not return for follow-up. 

Comment

GPD is characterized by a monomorphic papular eruption occurring in the perinasal, perioral, and periocular areas. Gianotti et al1 first described the condition in 5 children, ranging in age from 2 to 7 years, who had asymptomatic, distinctive, flesh-colored, "micronodular," periorificial eruptions. In the literature, the condition has been variably called Gianotti-type perioral dermatitis, sarcoidlike granulomatous dermatitis, facial Afro-Caribbean childhood eruption, and childhood granulomatous perioral dermatitis. It has been proposed that GPD is a form of perioral dermatitis with granulomatous histologic features.^2,3 GPD typically affects prepubertal children, predominantly African Americans and others with dark skin. Several cases involving fair-skinned children have been reported.² Both genders are equally affected. Typical lesions have been described as flesh-colored, yellow-brown, or red papules or micronodules.^2,3 Slight scaling of lesions or surrounding erythema may occur.² Scarring is absent in most cases; however, pinpoint atrophy or scarring occasionally occurs.² In addition to the characteristic facial distribution, extrafacial and generalized lesions on the trunk, extremities, and labia majora have been described.² In all reported cases, the lesions, including extrafacial lesions, were histologically similar and self-limited and were not accompanied by associated systemic symptoms. The presence of extrafacial lesions did not affect the duration of disease or the response to treatment.

The etiology of GPD is unknown. It may represent an unusual inflammatory granulomatous response to allergens.³ The initial allergen may cause inflammation and a focal disruption of the follicular wall, inciting a granulomatous reaction.³ In 1978, Georgouras and Kocsard4 described a case of Gianotti-type perioral dermatitis as an unusual reaction to bubble gum. Other reports have implicated reactions to formaldehyde, cosmetic preparations, and antiseptic solutions.⁵ Topical corticosteroids may induce or exacerbate both perioral dermatitis and GPD.^3,6

Histologic findings consist of upper dermal and perifollicular granulomas admixed with lymphocytes. The inflammation surrounding a focally disrupted hair follicle may range from a primarily lymphocytic inflammation with focal granuloma formation to a denser dermal granulomatous infiltrate. The presence of lymphocytic inflammation can help distinguish GPD from the "naked" granulomas in cutaneous sarcoidosis that typically lack inflammatory cells. GPD also may show epidermal change with mild to moderate spongiosis.^3,7

The clinical differential diagnosis of granulomatous papules on the face of a child includes GPD, granulomatous rosacea, lupus miliaris disseminatus faciei, and cutaneous sarcoidosis. Other cutaneous diseases that may occur in a periorificial distribution include perioral dermatitis, telangiectatic fibromas, and trichoepitheliomas. Although similar in distribution to GPD, the primary lesions in these latter 3 conditions are not granulomatous and can often be distinguished clinically. Deep fungal infection, atypical mycobacterial infection, and leishmaniasis can be considered in the histologic differential diagnosis of granulomatous dermatitis, but these conditions usually present as nodules, plaques, or ulcers and not necessarily in a perioral distribution.

Granulomatous rosacea and GPD have a similar clinical and histopathologic presentation. Both conditions can present as red or yellow-brown, dome-shaped facial papules with histologic findings of a perifollicular lymphohistiocytic or granulomatous infiltrate. The major distinguishing features of granulomatous rosacea are erythema, telangiectasias, pustules, and edema.8 Granulomatous rosacea is not characterized by a concentration of lesions in the perioral area, and it is most common in 30- to 50-year-old women.⁹ Rosacea also involves the eyes in about 17% of patients seen by dermatologists.¹⁰ Ocular rosacea can manifest as blepharitis, conjunctival injection, and chalazion.

Lupus miliaris disseminatus faciei is another chronic facial papular eruption with a high predilection for the eyelids. The lesions are usually red or yellow-brown dome-shaped papules. Histologic examination demonstrates well-formed granulomas with central caseation necrosis. Lesions resolve spontaneously in 12 to 24 months with scarring. To our knowledge, lupus miliaris disseminatus faciei has not been reported in children. It has been hypothesized that most patients with this eruption actually have a form of granulomatous rosacea.⁷

Sarcoidosis is a systemic granulomatous disease with cutaneous manifestations. Cutaneous involvement occurs in up to one third of patients and can present as macules, papules, nodules, plaques, subcutaneous nodules, infiltrative scars, and ichthyosis. Maculopapular lesions are the most common cutaneous manifestation of sarcoidosis and can occur anywhere on the skin.¹¹ Lupus pernio is a variant of sarcoidosis characterized by violaceous papules and plaques on the nasal alar rims, ears, and cheeks. This variant of sarcoidosis occurs most frequently in middle-aged women and is associated with chronic fibrotic respiratory tract involvement. Patients with cutaneous sarcoidosis may have systemic symptoms including weight loss, shortness of breath, cough, fatigue, and bone and joint pain.

Perioral dermatitis most commonly occurs in young women between 16 and 45 years of age. The characteristic eruption consists of pustular or papulovesicular lesions on an erythematous background.¹² The lesions are usually confined to the chin and nasolabial folds, with sparing around the vermilion border. GPD may be distinguished from perioral dermatitis by the presence of discrete yellow-brown papules rather than erythematous papules, the lack of pustules, and the presence of a perifollicular granulomatous infiltrate seen on examination of biopsy material.⁵

Treatment of GPD is based on anecdotal reports. Tetracycline has been recommended for GPD in children older than 8 years.^3,13 Recent studies have demonstrated that tetracyclines inhibit granuloma formation in vitro.¹⁴ Tetracyclines are also effective treatment for rosacea and perioral dermatitis because of their anti-inflammatory properties.¹⁵ According to anecdotal reports, topical tetracycline and topical clindamycin are sometimes effective therapy for perioral dermatitis and may be helpful in GPD when oral agents are undesirable. GPD also has responded to topical treatment with metronidazole gel in some reports.^3,16 Mild GPD may resolve spontaneously over several months without therapy. The use of oral steroids in this condition has not been reported, but in our patient, a tapering course of prednisone seemed justified because of the distressing nature of the eruption to the patient. Oral prednisone may produce anti-inflammatory effects more quickly than tetracycline, but it is not necessary in most patients.

GPD represents a benign cutaneous inflammatory process that resolves without serious sequelae. The granulomatous inflammation is most likely a nonspecific reaction to a variety of insults. Topical corticosteroids may initiate or exacerbate the granulomatous reaction and should be strictly avoided. Practitioners should recognize and distinguish this condition from other granulomatous eruptions so that patients are appropriately managed.

Case Report

A healthy 12-year-old African American boy presented with a 3-month history of an asymptomatic, papular, perioral eruption. He had been previously treated by a primary care provider, who had prescribed a low-potency and then a medium-potency topical corticosteroid, without improvement. The patient's parents denied that he had used topical corticosteroids or other topical preparations prior to the eruption. He took no oral medications, and the findings of the review of systems were within reference range. Results of a physical examination revealed numerous, discrete and coalescing, firm, pink, hyperpigmented papules ranging from 2 to 4 mm in diameter, primarily located in the perioral area (Figure). A few papules were noted around the nose and eyes. Results of a shave biopsy of a perioral papule revealed dermal granulomatous inflammation. The infiltrate consisted of histiocytes and lymphocytes and also included several focal collections of neutrophils. There was overlying parakeratosis. Results of a periodic acid–Schiff, Gomori methenamine-silver, Brown-Brenn, and Fite-Farraco stains were negative for organisms.

The patient was diagnosed with granulomatous periorificial dermatitis (GPD), and treatment with oral tetracycline 500 mg twice a day was initiated. Six days later, a tapering course of oral prednisone was added (consisting of 40 mg for 3 days, 30 mg for 3 days, 20 mg for 3 days, and 10 mg for 3 days) because of the severe extent of the eruption and the social distress it was causing the patient. Within 3 weeks, a dramatic decrease in the eruption was noted, with only a few small papules remaining. The patient was then switched from oral tetracycline to topical clindamycin twice a day for maintenance, but he did not return for follow-up. 

Comment

GPD is characterized by a monomorphic papular eruption occurring in the perinasal, perioral, and periocular areas. Gianotti et al1 first described the condition in 5 children, ranging in age from 2 to 7 years, who had asymptomatic, distinctive, flesh-colored, "micronodular," periorificial eruptions. In the literature, the condition has been variably called Gianotti-type perioral dermatitis, sarcoidlike granulomatous dermatitis, facial Afro-Caribbean childhood eruption, and childhood granulomatous perioral dermatitis. It has been proposed that GPD is a form of perioral dermatitis with granulomatous histologic features.^2,3 GPD typically affects prepubertal children, predominantly African Americans and others with dark skin. Several cases involving fair-skinned children have been reported.² Both genders are equally affected. Typical lesions have been described as flesh-colored, yellow-brown, or red papules or micronodules.^2,3 Slight scaling of lesions or surrounding erythema may occur.² Scarring is absent in most cases; however, pinpoint atrophy or scarring occasionally occurs.² In addition to the characteristic facial distribution, extrafacial and generalized lesions on the trunk, extremities, and labia majora have been described.² In all reported cases, the lesions, including extrafacial lesions, were histologically similar and self-limited and were not accompanied by associated systemic symptoms. The presence of extrafacial lesions did not affect the duration of disease or the response to treatment.

The etiology of GPD is unknown. It may represent an unusual inflammatory granulomatous response to allergens.³ The initial allergen may cause inflammation and a focal disruption of the follicular wall, inciting a granulomatous reaction.³ In 1978, Georgouras and Kocsard4 described a case of Gianotti-type perioral dermatitis as an unusual reaction to bubble gum. Other reports have implicated reactions to formaldehyde, cosmetic preparations, and antiseptic solutions.⁵ Topical corticosteroids may induce or exacerbate both perioral dermatitis and GPD.^3,6

Histologic findings consist of upper dermal and perifollicular granulomas admixed with lymphocytes. The inflammation surrounding a focally disrupted hair follicle may range from a primarily lymphocytic inflammation with focal granuloma formation to a denser dermal granulomatous infiltrate. The presence of lymphocytic inflammation can help distinguish GPD from the "naked" granulomas in cutaneous sarcoidosis that typically lack inflammatory cells. GPD also may show epidermal change with mild to moderate spongiosis.^3,7

The clinical differential diagnosis of granulomatous papules on the face of a child includes GPD, granulomatous rosacea, lupus miliaris disseminatus faciei, and cutaneous sarcoidosis. Other cutaneous diseases that may occur in a periorificial distribution include perioral dermatitis, telangiectatic fibromas, and trichoepitheliomas. Although similar in distribution to GPD, the primary lesions in these latter 3 conditions are not granulomatous and can often be distinguished clinically. Deep fungal infection, atypical mycobacterial infection, and leishmaniasis can be considered in the histologic differential diagnosis of granulomatous dermatitis, but these conditions usually present as nodules, plaques, or ulcers and not necessarily in a perioral distribution.

Granulomatous rosacea and GPD have a similar clinical and histopathologic presentation. Both conditions can present as red or yellow-brown, dome-shaped facial papules with histologic findings of a perifollicular lymphohistiocytic or granulomatous infiltrate. The major distinguishing features of granulomatous rosacea are erythema, telangiectasias, pustules, and edema.8 Granulomatous rosacea is not characterized by a concentration of lesions in the perioral area, and it is most common in 30- to 50-year-old women.⁹ Rosacea also involves the eyes in about 17% of patients seen by dermatologists.¹⁰ Ocular rosacea can manifest as blepharitis, conjunctival injection, and chalazion.

Lupus miliaris disseminatus faciei is another chronic facial papular eruption with a high predilection for the eyelids. The lesions are usually red or yellow-brown dome-shaped papules. Histologic examination demonstrates well-formed granulomas with central caseation necrosis. Lesions resolve spontaneously in 12 to 24 months with scarring. To our knowledge, lupus miliaris disseminatus faciei has not been reported in children. It has been hypothesized that most patients with this eruption actually have a form of granulomatous rosacea.⁷

Sarcoidosis is a systemic granulomatous disease with cutaneous manifestations. Cutaneous involvement occurs in up to one third of patients and can present as macules, papules, nodules, plaques, subcutaneous nodules, infiltrative scars, and ichthyosis. Maculopapular lesions are the most common cutaneous manifestation of sarcoidosis and can occur anywhere on the skin.¹¹ Lupus pernio is a variant of sarcoidosis characterized by violaceous papules and plaques on the nasal alar rims, ears, and cheeks. This variant of sarcoidosis occurs most frequently in middle-aged women and is associated with chronic fibrotic respiratory tract involvement. Patients with cutaneous sarcoidosis may have systemic symptoms including weight loss, shortness of breath, cough, fatigue, and bone and joint pain.

Perioral dermatitis most commonly occurs in young women between 16 and 45 years of age. The characteristic eruption consists of pustular or papulovesicular lesions on an erythematous background.¹² The lesions are usually confined to the chin and nasolabial folds, with sparing around the vermilion border. GPD may be distinguished from perioral dermatitis by the presence of discrete yellow-brown papules rather than erythematous papules, the lack of pustules, and the presence of a perifollicular granulomatous infiltrate seen on examination of biopsy material.⁵

Treatment of GPD is based on anecdotal reports. Tetracycline has been recommended for GPD in children older than 8 years.^3,13 Recent studies have demonstrated that tetracyclines inhibit granuloma formation in vitro.¹⁴ Tetracyclines are also effective treatment for rosacea and perioral dermatitis because of their anti-inflammatory properties.¹⁵ According to anecdotal reports, topical tetracycline and topical clindamycin are sometimes effective therapy for perioral dermatitis and may be helpful in GPD when oral agents are undesirable. GPD also has responded to topical treatment with metronidazole gel in some reports.^3,16 Mild GPD may resolve spontaneously over several months without therapy. The use of oral steroids in this condition has not been reported, but in our patient, a tapering course of prednisone seemed justified because of the distressing nature of the eruption to the patient. Oral prednisone may produce anti-inflammatory effects more quickly than tetracycline, but it is not necessary in most patients.

GPD represents a benign cutaneous inflammatory process that resolves without serious sequelae. The granulomatous inflammation is most likely a nonspecific reaction to a variety of insults. Topical corticosteroids may initiate or exacerbate the granulomatous reaction and should be strictly avoided. Practitioners should recognize and distinguish this condition from other granulomatous eruptions so that patients are appropriately managed.

Case Report

A healthy 12-year-old African American boy presented with a 3-month history of an asymptomatic, papular, perioral eruption. He had been previously treated by a primary care provider, who had prescribed a low-potency and then a medium-potency topical corticosteroid, without improvement. The patient's parents denied that he had used topical corticosteroids or other topical preparations prior to the eruption. He took no oral medications, and the findings of the review of systems were within reference range. Results of a physical examination revealed numerous, discrete and coalescing, firm, pink, hyperpigmented papules ranging from 2 to 4 mm in diameter, primarily located in the perioral area (Figure). A few papules were noted around the nose and eyes. Results of a shave biopsy of a perioral papule revealed dermal granulomatous inflammation. The infiltrate consisted of histiocytes and lymphocytes and also included several focal collections of neutrophils. There was overlying parakeratosis. Results of a periodic acid–Schiff, Gomori methenamine-silver, Brown-Brenn, and Fite-Farraco stains were negative for organisms.

The patient was diagnosed with granulomatous periorificial dermatitis (GPD), and treatment with oral tetracycline 500 mg twice a day was initiated. Six days later, a tapering course of oral prednisone was added (consisting of 40 mg for 3 days, 30 mg for 3 days, 20 mg for 3 days, and 10 mg for 3 days) because of the severe extent of the eruption and the social distress it was causing the patient. Within 3 weeks, a dramatic decrease in the eruption was noted, with only a few small papules remaining. The patient was then switched from oral tetracycline to topical clindamycin twice a day for maintenance, but he did not return for follow-up. 

Comment

GPD is characterized by a monomorphic papular eruption occurring in the perinasal, perioral, and periocular areas. Gianotti et al1 first described the condition in 5 children, ranging in age from 2 to 7 years, who had asymptomatic, distinctive, flesh-colored, "micronodular," periorificial eruptions. In the literature, the condition has been variably called Gianotti-type perioral dermatitis, sarcoidlike granulomatous dermatitis, facial Afro-Caribbean childhood eruption, and childhood granulomatous perioral dermatitis. It has been proposed that GPD is a form of perioral dermatitis with granulomatous histologic features.^2,3 GPD typically affects prepubertal children, predominantly African Americans and others with dark skin. Several cases involving fair-skinned children have been reported.² Both genders are equally affected. Typical lesions have been described as flesh-colored, yellow-brown, or red papules or micronodules.^2,3 Slight scaling of lesions or surrounding erythema may occur.² Scarring is absent in most cases; however, pinpoint atrophy or scarring occasionally occurs.² In addition to the characteristic facial distribution, extrafacial and generalized lesions on the trunk, extremities, and labia majora have been described.² In all reported cases, the lesions, including extrafacial lesions, were histologically similar and self-limited and were not accompanied by associated systemic symptoms. The presence of extrafacial lesions did not affect the duration of disease or the response to treatment.

The etiology of GPD is unknown. It may represent an unusual inflammatory granulomatous response to allergens.³ The initial allergen may cause inflammation and a focal disruption of the follicular wall, inciting a granulomatous reaction.³ In 1978, Georgouras and Kocsard4 described a case of Gianotti-type perioral dermatitis as an unusual reaction to bubble gum. Other reports have implicated reactions to formaldehyde, cosmetic preparations, and antiseptic solutions.⁵ Topical corticosteroids may induce or exacerbate both perioral dermatitis and GPD.^3,6

Histologic findings consist of upper dermal and perifollicular granulomas admixed with lymphocytes. The inflammation surrounding a focally disrupted hair follicle may range from a primarily lymphocytic inflammation with focal granuloma formation to a denser dermal granulomatous infiltrate. The presence of lymphocytic inflammation can help distinguish GPD from the "naked" granulomas in cutaneous sarcoidosis that typically lack inflammatory cells. GPD also may show epidermal change with mild to moderate spongiosis.^3,7

The clinical differential diagnosis of granulomatous papules on the face of a child includes GPD, granulomatous rosacea, lupus miliaris disseminatus faciei, and cutaneous sarcoidosis. Other cutaneous diseases that may occur in a periorificial distribution include perioral dermatitis, telangiectatic fibromas, and trichoepitheliomas. Although similar in distribution to GPD, the primary lesions in these latter 3 conditions are not granulomatous and can often be distinguished clinically. Deep fungal infection, atypical mycobacterial infection, and leishmaniasis can be considered in the histologic differential diagnosis of granulomatous dermatitis, but these conditions usually present as nodules, plaques, or ulcers and not necessarily in a perioral distribution.

Granulomatous rosacea and GPD have a similar clinical and histopathologic presentation. Both conditions can present as red or yellow-brown, dome-shaped facial papules with histologic findings of a perifollicular lymphohistiocytic or granulomatous infiltrate. The major distinguishing features of granulomatous rosacea are erythema, telangiectasias, pustules, and edema.8 Granulomatous rosacea is not characterized by a concentration of lesions in the perioral area, and it is most common in 30- to 50-year-old women.⁹ Rosacea also involves the eyes in about 17% of patients seen by dermatologists.¹⁰ Ocular rosacea can manifest as blepharitis, conjunctival injection, and chalazion.

Lupus miliaris disseminatus faciei is another chronic facial papular eruption with a high predilection for the eyelids. The lesions are usually red or yellow-brown dome-shaped papules. Histologic examination demonstrates well-formed granulomas with central caseation necrosis. Lesions resolve spontaneously in 12 to 24 months with scarring. To our knowledge, lupus miliaris disseminatus faciei has not been reported in children. It has been hypothesized that most patients with this eruption actually have a form of granulomatous rosacea.⁷

Sarcoidosis is a systemic granulomatous disease with cutaneous manifestations. Cutaneous involvement occurs in up to one third of patients and can present as macules, papules, nodules, plaques, subcutaneous nodules, infiltrative scars, and ichthyosis. Maculopapular lesions are the most common cutaneous manifestation of sarcoidosis and can occur anywhere on the skin.¹¹ Lupus pernio is a variant of sarcoidosis characterized by violaceous papules and plaques on the nasal alar rims, ears, and cheeks. This variant of sarcoidosis occurs most frequently in middle-aged women and is associated with chronic fibrotic respiratory tract involvement. Patients with cutaneous sarcoidosis may have systemic symptoms including weight loss, shortness of breath, cough, fatigue, and bone and joint pain.

Perioral dermatitis most commonly occurs in young women between 16 and 45 years of age. The characteristic eruption consists of pustular or papulovesicular lesions on an erythematous background.¹² The lesions are usually confined to the chin and nasolabial folds, with sparing around the vermilion border. GPD may be distinguished from perioral dermatitis by the presence of discrete yellow-brown papules rather than erythematous papules, the lack of pustules, and the presence of a perifollicular granulomatous infiltrate seen on examination of biopsy material.⁵

Treatment of GPD is based on anecdotal reports. Tetracycline has been recommended for GPD in children older than 8 years.^3,13 Recent studies have demonstrated that tetracyclines inhibit granuloma formation in vitro.¹⁴ Tetracyclines are also effective treatment for rosacea and perioral dermatitis because of their anti-inflammatory properties.¹⁵ According to anecdotal reports, topical tetracycline and topical clindamycin are sometimes effective therapy for perioral dermatitis and may be helpful in GPD when oral agents are undesirable. GPD also has responded to topical treatment with metronidazole gel in some reports.^3,16 Mild GPD may resolve spontaneously over several months without therapy. The use of oral steroids in this condition has not been reported, but in our patient, a tapering course of prednisone seemed justified because of the distressing nature of the eruption to the patient. Oral prednisone may produce anti-inflammatory effects more quickly than tetracycline, but it is not necessary in most patients.

GPD represents a benign cutaneous inflammatory process that resolves without serious sequelae. The granulomatous inflammation is most likely a nonspecific reaction to a variety of insults. Topical corticosteroids may initiate or exacerbate the granulomatous reaction and should be strictly avoided. Practitioners should recognize and distinguish this condition from other granulomatous eruptions so that patients are appropriately managed.