A 67-year-old woman presented with a 3-year history of difficulty smiling and swelling of the lower right half of her lip. Examination revealed enlargement of the lower right side of her lip and difficulty raising the right side of her mouth to form a smile (above). She was able to raise her eyebrows bilaterally. The lower right half of her lip was firm and non-tender. Further examination of her oral cavity revealed teeth in good repair without impaction. A midline fissure and adjacent furrows were present on the dorsal tongue (right).
WHAT IS YOUR DIAGNOSIS?
See below for an answer and for more details.
Diagnosis: Melkersson-Rosenthal Syndrome
Melkersson-Rosenthal syndrome is a rare disorder of unknown etiology classically described as a triad of orofacial swelling, facial palsy and fissured tongue. The relationship between the orofacial swelling and facial paralysis was first reported by Melkersson in 1928. 1 Later, Rosenthal described the finding of lingua plicata in association with the orofacial edema and facial nerve palsy. 2 In 1949, the triad became known as the Melkersson-Rosenthal syndrome. 2 However, the classic triad is not always present; more often the disorder presents in an oligosymptomatic form, complicating the diagnosis. Melkersson-Rosenthal syndrome and its oligosymptomatic and monosymptomatic forms can be included under the category of orofacial granulomatosis. The concept of orofacial granulomatosis was defined by Wisenfield and colleagues in 1985. 3 The category encompasses the previously recognized clinical entities of Melkersson-Rosenthal syndrome and cheilitis granulomatosa.3 The pathological features include the presence of multiple, non-caseating granulomas that are indistinguishable from those found in Crohn’s disease and systemic sarcoidosis.3
Clinical Presentation
Melkersson-Rosenthal syndrome can present with recurrent orofacial swelling — predominately involving the lips — along with facial nerve palsy and lingua plicata. The complete triad is uncommon; the incomplete monosymptomatic and oligosymptomatic forms of Melkersson-Rosenthal syndrome can include Miescher’s cheilitis granulomatosa or a combination of any two of the clinical features of the triad.1 While Melkersson-Rosenthal syndrome has been reported in both young and old patients, the disorder typically begins in the second decade of life.1,4 Frequently, there is a fluctuating course, and the various signs of the syndrome can appear at different intervals. The facial swelling and facial nerve paralysis may initially be intermittent but can eventually become permanent.1,5 Most authors report an equal gender distribution with no racial or ethnic predilection. 1,2,4 Orofacial edema is the most common presenting sign of Melkersson-Rosenthal syndrome, occurring in approximately 69% of cases.4 The edema is typically non-pitting, non-pruritic and painless, with peripheral erythema.6 Tissues involved include the chin, cheeks, eyelids, lips and nose.1,6 The most frequent site of involvement is the upper lip, and significant swelling can cause a chapped or fissured appearance.6 Severe swelling can interfere with eating and speaking. Recurrent facial nerve palsy has been reported in approximately 47% of patients with Melkersson-Rosenthal syndrome.2 The facial paralysis can be sudden in onset and typically occurs unilaterally, making it indistinguishable from Bell’s palsy.1 Lingua plicata may occur in 50% to 60% of patients with Melkersson-Rosenthal syndrome.2,5 Clinically it presents as a fissured tongue with deep furrows on the dorsal surface that can extend in all directions, similar to our patient (Figure 2). Macroglossia can occur secondarily from chronic inflammation due to bacterial and/or mycotic infections occurring in the grooves.1 Delay in diagnosis can occur due to the infrequent nature and/or the lack of awareness of Melkersson-Rosenthal syndrome. Proper diagnosis requires a thorough patient history and physical exam. As orofacial swelling is the most common presenting sign, histological evaluation to determine the cause of the swelling is important. Diagnosis can be aided by histology, laboratory tests and physical findings to rule out other causes of orofacial granulomatosis.
Pathology
Biopsies are commonly obtained from the lip in patients with Melkersson-Rosenthal syndrome.1 Microscopic examination demonstrates non-caseating granulomas with mild edema and perivascular lymphocytic inflammation.1 Mild epithelial hyperplasia may also be seen. Established lesions typically have non-caseating granulomas scattered throughout the dermis or lamina propria; however, granulomas may form and resolve within days. Thus, negative histological findings do not exclude the diagnosis of Melkersson-Rosenthal syndrome.1
Differential Diagnosis
Several conditions, described below, can present with facial swelling similar to Melkersson-Rosenthal syndrome (Table 1).1,2,4,5,6 The diagnosis is typically difficult to establish, as classical features are not always present. Correlation of history and clinical data can help aid in diagnosis. Crohn’s disease is a type of inflammatory bowel disease that typically manifests with gastrointestinal complaints. Like other chronic inflammatory diseases, Crohn’s disease may present with a variety of systemic signs, including erythema nodosum and migratory polyarthritis. Histologically, it is characterized by noncaseating granulomas and lymphoid aggregates. Hereditary angioedema is a genetic disorder characterized by low levels or a dysfunctional C1 esterase inhibitor.7 Clinically, the disorder manifests as recurrent attacks of massive, localized non-pitting edema without concomitant pruritus. Facial areas typically involved are the eyelids, lips and tongue. In patients with suspected hereditary angioedema, complement levels and serum measurements of C1 esterase inhibitor activity can be utilized in diagnosis.7 Erysipelas is a superficial bacterial skin infection typically caused by group A Streptococcus bacteria. Recurrent erysipelas can present as localized erythema that is indurated, tender and warm. Patients typically develop symptoms including chills, fever, headache and fatigue.8
Pathogenesis
The etiology of Melkersson-Rosenthal syndrome remains unknown. Infection has been suggested as a potential cause of the disorder with case reports of the disease occurring in association with bacterial infections and syphilis.6,9 Facial nerve palsy has been proposed to occur due to nerve compression, as facial paralysis typically occurs on the same side as accompanying orofacial swelling.1 Delayed-type hypersensitivity to foods and cosmetic additives have also been proposed as potential causes.10 The inheritance pattern for Melkersson-Rosenthal syndrome is believed to be autosomal dominant with the implicated gene mapped to 9p11.5 However, hypotheses describing allergies, genetic and infectious agents as the cause of the syndrome have not been established.
Treatment
Treatment for Melkersson-Rosenthal syndrome is largely symptomatic as no standard treatment option currently exists. Cold compresses can be utilized for acute facial swelling. Topical ointments can be utilized to prevent fissuring of the lips. Surgical interventions, such as decompression of the facial nerve, can be utilized for prolonged facial palsy.1 Additionally, allergy testing and searching for dental infections can be performed. Topical, intralesional and systemic corticosteroids have been utilized with some success in patients with Melkersson-Rosenthal syndrome.1,2 Several other agents have been effective in treatment, including clofazimine, dapsone, erythromycin, hydroxychloroquine, minocycline, penicillin and tetracycline. 1,2,4,6
Conclusion
The key to establishing the diagnosis of Melkersson-Rosenthal syndrome in patients who present with recurrent facial swelling, facial nerve palsy, or fissuring of the tongue is entertaining the possibility. A complete history and physical exam can provide important clues to aid in the diagnosis. With a variable presentation, an index of suspicion must be maintained and other causes ruled out to establish a diagnosis of Melkersson-Rosenthal syndrome. Mr. Riahi is a medical student at the Medical School, The University of Texas Medical Branch, Galveston, TX. Dr. Cohen is with the University of Houston Health Center, University of Houston, Houston, Texas, the Department of Dermatology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, and the Department of Dermatology, University of Texas-Houston Medical School, Houston, TX. Dr. Khachemoune, the Section Editor of Derm Dx, is with Department of Dermatology, State University of New York, Brooklyn, NY. Disclosure: The authors have no conflicts of interest or financial disclosures to report.
A 67-year-old woman presented with a 3-year history of difficulty smiling and swelling of the lower right half of her lip. Examination revealed enlargement of the lower right side of her lip and difficulty raising the right side of her mouth to form a smile (above). She was able to raise her eyebrows bilaterally. The lower right half of her lip was firm and non-tender. Further examination of her oral cavity revealed teeth in good repair without impaction. A midline fissure and adjacent furrows were present on the dorsal tongue (right).
WHAT IS YOUR DIAGNOSIS?
See below for an answer and for more details.
Diagnosis: Melkersson-Rosenthal Syndrome
Melkersson-Rosenthal syndrome is a rare disorder of unknown etiology classically described as a triad of orofacial swelling, facial palsy and fissured tongue. The relationship between the orofacial swelling and facial paralysis was first reported by Melkersson in 1928. 1 Later, Rosenthal described the finding of lingua plicata in association with the orofacial edema and facial nerve palsy. 2 In 1949, the triad became known as the Melkersson-Rosenthal syndrome. 2 However, the classic triad is not always present; more often the disorder presents in an oligosymptomatic form, complicating the diagnosis. Melkersson-Rosenthal syndrome and its oligosymptomatic and monosymptomatic forms can be included under the category of orofacial granulomatosis. The concept of orofacial granulomatosis was defined by Wisenfield and colleagues in 1985. 3 The category encompasses the previously recognized clinical entities of Melkersson-Rosenthal syndrome and cheilitis granulomatosa.3 The pathological features include the presence of multiple, non-caseating granulomas that are indistinguishable from those found in Crohn’s disease and systemic sarcoidosis.3
Clinical Presentation
Melkersson-Rosenthal syndrome can present with recurrent orofacial swelling — predominately involving the lips — along with facial nerve palsy and lingua plicata. The complete triad is uncommon; the incomplete monosymptomatic and oligosymptomatic forms of Melkersson-Rosenthal syndrome can include Miescher’s cheilitis granulomatosa or a combination of any two of the clinical features of the triad.1 While Melkersson-Rosenthal syndrome has been reported in both young and old patients, the disorder typically begins in the second decade of life.1,4 Frequently, there is a fluctuating course, and the various signs of the syndrome can appear at different intervals. The facial swelling and facial nerve paralysis may initially be intermittent but can eventually become permanent.1,5 Most authors report an equal gender distribution with no racial or ethnic predilection. 1,2,4 Orofacial edema is the most common presenting sign of Melkersson-Rosenthal syndrome, occurring in approximately 69% of cases.4 The edema is typically non-pitting, non-pruritic and painless, with peripheral erythema.6 Tissues involved include the chin, cheeks, eyelids, lips and nose.1,6 The most frequent site of involvement is the upper lip, and significant swelling can cause a chapped or fissured appearance.6 Severe swelling can interfere with eating and speaking. Recurrent facial nerve palsy has been reported in approximately 47% of patients with Melkersson-Rosenthal syndrome.2 The facial paralysis can be sudden in onset and typically occurs unilaterally, making it indistinguishable from Bell’s palsy.1 Lingua plicata may occur in 50% to 60% of patients with Melkersson-Rosenthal syndrome.2,5 Clinically it presents as a fissured tongue with deep furrows on the dorsal surface that can extend in all directions, similar to our patient (Figure 2). Macroglossia can occur secondarily from chronic inflammation due to bacterial and/or mycotic infections occurring in the grooves.1 Delay in diagnosis can occur due to the infrequent nature and/or the lack of awareness of Melkersson-Rosenthal syndrome. Proper diagnosis requires a thorough patient history and physical exam. As orofacial swelling is the most common presenting sign, histological evaluation to determine the cause of the swelling is important. Diagnosis can be aided by histology, laboratory tests and physical findings to rule out other causes of orofacial granulomatosis.
Pathology
Biopsies are commonly obtained from the lip in patients with Melkersson-Rosenthal syndrome.1 Microscopic examination demonstrates non-caseating granulomas with mild edema and perivascular lymphocytic inflammation.1 Mild epithelial hyperplasia may also be seen. Established lesions typically have non-caseating granulomas scattered throughout the dermis or lamina propria; however, granulomas may form and resolve within days. Thus, negative histological findings do not exclude the diagnosis of Melkersson-Rosenthal syndrome.1
Differential Diagnosis
Several conditions, described below, can present with facial swelling similar to Melkersson-Rosenthal syndrome (Table 1).1,2,4,5,6 The diagnosis is typically difficult to establish, as classical features are not always present. Correlation of history and clinical data can help aid in diagnosis. Crohn’s disease is a type of inflammatory bowel disease that typically manifests with gastrointestinal complaints. Like other chronic inflammatory diseases, Crohn’s disease may present with a variety of systemic signs, including erythema nodosum and migratory polyarthritis. Histologically, it is characterized by noncaseating granulomas and lymphoid aggregates. Hereditary angioedema is a genetic disorder characterized by low levels or a dysfunctional C1 esterase inhibitor.7 Clinically, the disorder manifests as recurrent attacks of massive, localized non-pitting edema without concomitant pruritus. Facial areas typically involved are the eyelids, lips and tongue. In patients with suspected hereditary angioedema, complement levels and serum measurements of C1 esterase inhibitor activity can be utilized in diagnosis.7 Erysipelas is a superficial bacterial skin infection typically caused by group A Streptococcus bacteria. Recurrent erysipelas can present as localized erythema that is indurated, tender and warm. Patients typically develop symptoms including chills, fever, headache and fatigue.8
Pathogenesis
The etiology of Melkersson-Rosenthal syndrome remains unknown. Infection has been suggested as a potential cause of the disorder with case reports of the disease occurring in association with bacterial infections and syphilis.6,9 Facial nerve palsy has been proposed to occur due to nerve compression, as facial paralysis typically occurs on the same side as accompanying orofacial swelling.1 Delayed-type hypersensitivity to foods and cosmetic additives have also been proposed as potential causes.10 The inheritance pattern for Melkersson-Rosenthal syndrome is believed to be autosomal dominant with the implicated gene mapped to 9p11.5 However, hypotheses describing allergies, genetic and infectious agents as the cause of the syndrome have not been established.
Treatment
Treatment for Melkersson-Rosenthal syndrome is largely symptomatic as no standard treatment option currently exists. Cold compresses can be utilized for acute facial swelling. Topical ointments can be utilized to prevent fissuring of the lips. Surgical interventions, such as decompression of the facial nerve, can be utilized for prolonged facial palsy.1 Additionally, allergy testing and searching for dental infections can be performed. Topical, intralesional and systemic corticosteroids have been utilized with some success in patients with Melkersson-Rosenthal syndrome.1,2 Several other agents have been effective in treatment, including clofazimine, dapsone, erythromycin, hydroxychloroquine, minocycline, penicillin and tetracycline. 1,2,4,6
Conclusion
The key to establishing the diagnosis of Melkersson-Rosenthal syndrome in patients who present with recurrent facial swelling, facial nerve palsy, or fissuring of the tongue is entertaining the possibility. A complete history and physical exam can provide important clues to aid in the diagnosis. With a variable presentation, an index of suspicion must be maintained and other causes ruled out to establish a diagnosis of Melkersson-Rosenthal syndrome. Mr. Riahi is a medical student at the Medical School, The University of Texas Medical Branch, Galveston, TX. Dr. Cohen is with the University of Houston Health Center, University of Houston, Houston, Texas, the Department of Dermatology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, and the Department of Dermatology, University of Texas-Houston Medical School, Houston, TX. Dr. Khachemoune, the Section Editor of Derm Dx, is with Department of Dermatology, State University of New York, Brooklyn, NY. Disclosure: The authors have no conflicts of interest or financial disclosures to report.
A 67-year-old woman presented with a 3-year history of difficulty smiling and swelling of the lower right half of her lip. Examination revealed enlargement of the lower right side of her lip and difficulty raising the right side of her mouth to form a smile (above). She was able to raise her eyebrows bilaterally. The lower right half of her lip was firm and non-tender. Further examination of her oral cavity revealed teeth in good repair without impaction. A midline fissure and adjacent furrows were present on the dorsal tongue (right).
WHAT IS YOUR DIAGNOSIS?
See below for an answer and for more details.
Diagnosis: Melkersson-Rosenthal Syndrome
Melkersson-Rosenthal syndrome is a rare disorder of unknown etiology classically described as a triad of orofacial swelling, facial palsy and fissured tongue. The relationship between the orofacial swelling and facial paralysis was first reported by Melkersson in 1928. 1 Later, Rosenthal described the finding of lingua plicata in association with the orofacial edema and facial nerve palsy. 2 In 1949, the triad became known as the Melkersson-Rosenthal syndrome. 2 However, the classic triad is not always present; more often the disorder presents in an oligosymptomatic form, complicating the diagnosis. Melkersson-Rosenthal syndrome and its oligosymptomatic and monosymptomatic forms can be included under the category of orofacial granulomatosis. The concept of orofacial granulomatosis was defined by Wisenfield and colleagues in 1985. 3 The category encompasses the previously recognized clinical entities of Melkersson-Rosenthal syndrome and cheilitis granulomatosa.3 The pathological features include the presence of multiple, non-caseating granulomas that are indistinguishable from those found in Crohn’s disease and systemic sarcoidosis.3
Clinical Presentation
Melkersson-Rosenthal syndrome can present with recurrent orofacial swelling — predominately involving the lips — along with facial nerve palsy and lingua plicata. The complete triad is uncommon; the incomplete monosymptomatic and oligosymptomatic forms of Melkersson-Rosenthal syndrome can include Miescher’s cheilitis granulomatosa or a combination of any two of the clinical features of the triad.1 While Melkersson-Rosenthal syndrome has been reported in both young and old patients, the disorder typically begins in the second decade of life.1,4 Frequently, there is a fluctuating course, and the various signs of the syndrome can appear at different intervals. The facial swelling and facial nerve paralysis may initially be intermittent but can eventually become permanent.1,5 Most authors report an equal gender distribution with no racial or ethnic predilection. 1,2,4 Orofacial edema is the most common presenting sign of Melkersson-Rosenthal syndrome, occurring in approximately 69% of cases.4 The edema is typically non-pitting, non-pruritic and painless, with peripheral erythema.6 Tissues involved include the chin, cheeks, eyelids, lips and nose.1,6 The most frequent site of involvement is the upper lip, and significant swelling can cause a chapped or fissured appearance.6 Severe swelling can interfere with eating and speaking. Recurrent facial nerve palsy has been reported in approximately 47% of patients with Melkersson-Rosenthal syndrome.2 The facial paralysis can be sudden in onset and typically occurs unilaterally, making it indistinguishable from Bell’s palsy.1 Lingua plicata may occur in 50% to 60% of patients with Melkersson-Rosenthal syndrome.2,5 Clinically it presents as a fissured tongue with deep furrows on the dorsal surface that can extend in all directions, similar to our patient (Figure 2). Macroglossia can occur secondarily from chronic inflammation due to bacterial and/or mycotic infections occurring in the grooves.1 Delay in diagnosis can occur due to the infrequent nature and/or the lack of awareness of Melkersson-Rosenthal syndrome. Proper diagnosis requires a thorough patient history and physical exam. As orofacial swelling is the most common presenting sign, histological evaluation to determine the cause of the swelling is important. Diagnosis can be aided by histology, laboratory tests and physical findings to rule out other causes of orofacial granulomatosis.
Pathology
Biopsies are commonly obtained from the lip in patients with Melkersson-Rosenthal syndrome.1 Microscopic examination demonstrates non-caseating granulomas with mild edema and perivascular lymphocytic inflammation.1 Mild epithelial hyperplasia may also be seen. Established lesions typically have non-caseating granulomas scattered throughout the dermis or lamina propria; however, granulomas may form and resolve within days. Thus, negative histological findings do not exclude the diagnosis of Melkersson-Rosenthal syndrome.1
Differential Diagnosis
Several conditions, described below, can present with facial swelling similar to Melkersson-Rosenthal syndrome (Table 1).1,2,4,5,6 The diagnosis is typically difficult to establish, as classical features are not always present. Correlation of history and clinical data can help aid in diagnosis. Crohn’s disease is a type of inflammatory bowel disease that typically manifests with gastrointestinal complaints. Like other chronic inflammatory diseases, Crohn’s disease may present with a variety of systemic signs, including erythema nodosum and migratory polyarthritis. Histologically, it is characterized by noncaseating granulomas and lymphoid aggregates. Hereditary angioedema is a genetic disorder characterized by low levels or a dysfunctional C1 esterase inhibitor.7 Clinically, the disorder manifests as recurrent attacks of massive, localized non-pitting edema without concomitant pruritus. Facial areas typically involved are the eyelids, lips and tongue. In patients with suspected hereditary angioedema, complement levels and serum measurements of C1 esterase inhibitor activity can be utilized in diagnosis.7 Erysipelas is a superficial bacterial skin infection typically caused by group A Streptococcus bacteria. Recurrent erysipelas can present as localized erythema that is indurated, tender and warm. Patients typically develop symptoms including chills, fever, headache and fatigue.8
Pathogenesis
The etiology of Melkersson-Rosenthal syndrome remains unknown. Infection has been suggested as a potential cause of the disorder with case reports of the disease occurring in association with bacterial infections and syphilis.6,9 Facial nerve palsy has been proposed to occur due to nerve compression, as facial paralysis typically occurs on the same side as accompanying orofacial swelling.1 Delayed-type hypersensitivity to foods and cosmetic additives have also been proposed as potential causes.10 The inheritance pattern for Melkersson-Rosenthal syndrome is believed to be autosomal dominant with the implicated gene mapped to 9p11.5 However, hypotheses describing allergies, genetic and infectious agents as the cause of the syndrome have not been established.
Treatment
Treatment for Melkersson-Rosenthal syndrome is largely symptomatic as no standard treatment option currently exists. Cold compresses can be utilized for acute facial swelling. Topical ointments can be utilized to prevent fissuring of the lips. Surgical interventions, such as decompression of the facial nerve, can be utilized for prolonged facial palsy.1 Additionally, allergy testing and searching for dental infections can be performed. Topical, intralesional and systemic corticosteroids have been utilized with some success in patients with Melkersson-Rosenthal syndrome.1,2 Several other agents have been effective in treatment, including clofazimine, dapsone, erythromycin, hydroxychloroquine, minocycline, penicillin and tetracycline. 1,2,4,6
Conclusion
The key to establishing the diagnosis of Melkersson-Rosenthal syndrome in patients who present with recurrent facial swelling, facial nerve palsy, or fissuring of the tongue is entertaining the possibility. A complete history and physical exam can provide important clues to aid in the diagnosis. With a variable presentation, an index of suspicion must be maintained and other causes ruled out to establish a diagnosis of Melkersson-Rosenthal syndrome. Mr. Riahi is a medical student at the Medical School, The University of Texas Medical Branch, Galveston, TX. Dr. Cohen is with the University of Houston Health Center, University of Houston, Houston, Texas, the Department of Dermatology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, and the Department of Dermatology, University of Texas-Houston Medical School, Houston, TX. Dr. Khachemoune, the Section Editor of Derm Dx, is with Department of Dermatology, State University of New York, Brooklyn, NY. Disclosure: The authors have no conflicts of interest or financial disclosures to report.
