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Solid facial edema: Treatment failure with oral isotretinoin monotherapy and combination oral isotretinoin and oral steroid therapy

  • Author(s): Patel, Anisha B
  • Harting, Mandy S
  • Hsu, Sylvia
  • et al.
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Solid facial edema: Treatment failure with oral isotretinoin monotherapy and combination oral isotretinoin and oral steroid therapy
Anisha B Patel MD, Mandy S Harting MD, Sylvia Hsu MD
Dermatology Online Journal 14 (1): 14

Department of Dermatology, Baylor College of Medicine, Houston, Texas

Solid facial edema is a rare condition most commonly associated with acne vulgaris. The clinical presentation is consistent with localized, symmetric, non-pitting, non-painful edema over the glabellar region, midface, nasal saddle, and infraorbital regions. Most reported cases are males in their late teens or early twenties who present with a multi-year history of acne followed by a recent onset of persistent edema [1-11]. The pathogenesis is not well defined, making this condition difficult to treat [4, 12, 13]. Hot water injections, x-ray radiation, and topical steroids have been used in the past [1, 2], and more recently, oral antibiotics, oral steroids, isotretinoin, and surgical procedures have had varying degrees of success [1-21].

Only one previous case reported a failure of isotretinoin therapy in solid facial edema [2]. Herein, we report a patient with solid facial edema who failed a 4-month course of isotretinoin monotherapy and a 1-month course of oral prednisone in combination with isotretinoin. We also discuss the differential diagnosis and various treatment options.


Clinical synopsis


Figure 1

A 24-year-old man with a 10-year history of acne vulgaris presented with 1½ year history of persistent edema and erythema of the midface, infraorbital regions (right > left), glabellar region, and nasal saddle. (Fig. 1) The swelling is non-painful and non-pitting, but is greater in the morning. He also has erythematous papules with few pustules across his cheeks and nose. The patient has no cranial nerve deficits, visual impairments, fever, or chills. He is otherwise healthy and has not had any recent trauma to the face, acne flares, or facial injections. He works in a steel fabrication plant and is exposed to various chemicals, although he does not have redness or swelling anywhere else on his body. He was treated by multiple doctors, including a dermatologist and otolaryngologist, with topical steroids, oral cephalexin, oral cefuroxime, amoxicillin/clavulanate, and oral and topical clindamycin without improvement.

An MRI of the orbits was performed by an otolaryngologist to rule out a vascular tumor. Results included diffuse thickening of the soft tissues of the right lower lid without a discrete mass or drainable fluid collections. There was mucosal thickening along the walls of both maxillary sinuses (right > left) indicating chronic inflammatory changes. A vascular malformation was ruled out.

The patient was referred to dermatology for possible skin biopsy. The patient presented in such a classic manner that a punch biopsy of the face was not considered necessary to confirm his condition. The patient was started on oral isotretinoin at a 1mg/kg/day dose. After three months of isotretinoin, the patient's acne and the erythema had resolved, and there was minimal improvement of edema. The patient states that his edema is now stable throughout the entire day, without any morning exacerbations. Oral prednisone, 30 mg daily, was added to his isotretinoin regimen for one month without any improvement. The patient did not feel that he had significant improvement on either isotretinoin monotherapy or combination isotretinoin and prednisone therapy; therefore, he elected to discontinue all therapy.


Comments

Over 20 cases of solid facial edema have been reported, each providing new information regarding the etiology and treatment efficacies [1-11]. Most cases are associated with a history of acne vulgaris, with a 2-5 year delay before onset of edema in young men [4, 7]. The course of the acne and the course of the edema have not yet been correlated [6, 9].

Solid facial edema was first reported in 1966 in a patient who, over the course of 7 years developed edema, chronic inflammation, and eventual dermal fibrosis. The etiology of the solid facial edema was unknown at the time [14]. The first cases of solid facial edema secondary to acne reported were in 1985, and included some hypotheses as to its pathogenesis [1], but this still remains unclear [1, 4, 6, 7, 10, 13, 14]. A case of identical twin boys who had similar histories of acne with simultaneous onset of solid facial edema suggests a possible hereditary linkage [9]. Three cases have been reported in which there were histories of repeated facial blunt trauma [16] or a recent history of blunt trauma to the face [1, 6].

The most popular hypothesis regarding its etiology is that the chronic inflammation of acne causes damage to the lymphatic vessels, which explains why the edema does not subside even when the acne is treated. Further, the increased mast cells may result in fibrosis [1, 6, 7, 10, 14]. This theory is analogous to chronic cellulitis of the lower legs leading to lymphatic deficiency [1, 4, 6, 7, 8, 9]. Based on this theory, Camacho-Martinez and Winkelmann hypothesize that solid facial edema can only be treated with isotretinoin early in its course, before lymphatic damage is too severe [10]. Yet, according to Dwyer et al. antibiotics therapy can be beneficial and cause a slow, subsequent resolution of the edema [11].

The common differential diagnosis of solid facial edema includes acne, lymphedema of rosacea, Morbihan disease, and Melkersson-Rosenthal syndrome. Some believe that these conditions are identical and are only distinguished based on their etiologies [13, 22]. All of these conditions have similar histological findings of edema in the lower, upper, and mid dermis, perivascular and periadnexal inflammatory infiltrates, and a normal epidermis [1, 4, 7, 10, 11, 13, 14, 15]. There have been some reports of increased mast cell infiltrates, which are believed to cause dermal fibrosis [4, 7, 13, 15].

These conditions are, however, readily distinguished clinically. Lymphedema of rosacea has a history of rosacea and superficial dilated blood vessels [16, 18, 19, 20]. Morbihan disease is considered to be an idiopathic form of solid facial edema [15, 22, 23, 24]. A study by Wohlrab et al., however, showed that Morbihan disease may be attributed to a combination of poor lymphatic drainage and subclinical inflammation from immunologic contact urticaria [25]. Finally, Melkersson-Rosenthal syndrome is solid facial edema, usually lip edema, with associated scrotal tongue, peripheral facial nerve defect, and noncaseating granulomas [12, 26, 27].

There have been a few reported cases of solid facial edema secondary to rare causes. There is a reported case of retro-orbital B-cell lymphoma presenting as solid facial edema. However, in this case, there was also diplopia, eye pain, and more localized onset with peripheral spread. A case was reported of a child with solid facial edema who had generalized facial swelling 8 years after being stung by numerous bees, some of whose stingers were surgically removed months after the attack [28]. Another case was of a patient with a foreign body implant after a nasal fracture who presented years later with mid face swelling. Yet, in this case, his solid facial edema was believed to result from chronic inflammation that caused lymphatic vessel damage and foreign body granuloma [29].

Because solid facial edema is so difficult to treat, many cases address the different therapeutic options [1-13]. As solid facial edema of acne, rosaceous lymphedema, and Morbihan disease present similarly histologically and clinically, and are becoming more widely accepted as variations of the same condition, the treatment options for all three diseases will be discussed simultaneously. Oral isotrentinoin is the treatment with the most documented successful outcomes for solid facial edema of acne [4, 5, 6, 7, 10], rosaceous lymphedema [13], and Morbihan disease [17]. Isotretinoin has anti-inflammatory properties that decrease macrophage migration [7]. In one case, it was combined with clofazamine, a phenazine imiquimod derivative that decreases phagocytosis and macrophage functions [7]. Isotretinoin has also been used with ketotifen, which is a benzocycloheptathiophene that antagonizes mediator release from mast cells [4, 17]. All of the previously reported cases of solid facial edema treated with isotretinoin used between 0.5 and 1.0 mg/kg/day treatment [5, 6, 7, 10, 17] except for two cases that used 0.1-0.2 mg/kg/day [4 ,13]. Both low dose treatments were combined with ketotifen [4, 13]. The case reported here is the second reported case of treatment failure with isotretinoin therapy.

The use of oral steroids have resulted in a variety of outcomes, from long-term improvement in facial swelling [3, 16], to temporary improvement of facial swelling [7, 10, 30], to no improvement of facial swelling [9, 11, 15, 17, 21]. There is little evidence to support the efficacy of systemic steroids; in the case presented here, systemic steroid therapy was ineffective.

Antibiotics are generally believed to be ineffective [1-4, 6, 7, 9, 10, 15-17, 21] except for the one case in which facial swelling resolved over a period of months after the acne was treated with antibiotics [11]. Lymphatic massage has been a useful adjuvant treatment, but compression garments are only useful for temporary reduction of swelling [14]. There is no consistent evidence about the use of gamma interferon, hot water injections, x-ray radiation, antihistamines, or diuretics [11, 12, 14, 17].

Debulking surgery has been done for lymphedema of rosacea and Melkersson-Rosenthal syndrome with successful outcomes [12, 31, 32]. Other symptomatic treatments include CO2 laser blepharoplasty for eye lid swelling and liposuction of the face, which was used in the generalized facial edema presenting after multiple bee stings [23, 28].


Conclusion

Aesthetic deformity, decreased self esteem, and visual obstruction are the main sequelae of this disease [25, 28, 32]. Although there have been many reported treatment options in the literature, no single therapy has proven to be effective in all patients. Our case reports a treatment failure of solid facial edema, despite treatment with oral isotretinoin monotherapy and combination oral steroids and isotretinoin. Solid facial edema remains a treatment conundrum. As more cases of this rare condition are seen and reported, effective treatment options can be further explored.

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