Introduction

Acne vulgaris is a disorder of the pilosebaceous unit, namely the sebaceous gland and the hair follicle it is attached to. Some 85% of people have acne at some point in their life, especially during puberty [1], and therefore it could be considered the most common inflammatory skin disease. Due to disfiguration and scarring, the disease has major effects on the patient’s quality of life [2], eliciting depression, social withdrawal, anxiety and a higher rate of unemployment [3, 4].

The pathogenesis includes several components whose interplay is only partially known. The androgen surge in puberty stimulates the sebocytes and follicular keratinocytes that proliferate and obstruct the outflow tract of the hair follicle. This leads to a hyperplasia of the sebaceous glands and the seborrhea that is characteristic for acne. Propionibacterium acnes, an opportunistic grampositive anaerobic strain found in the seborrheic areas of the skin, breaks down fatty acids. These compounds are believed to elicit inflammation and chemotaxis of neutrophil granulocytes and adaptive immune cells to the follicular epithelium. This ends in the rupture and release of sebum, microorganisms and keratin into the dermis. Accumulation of neutrophils, lymphocytes and foreign-body giant cells leads to the characteristic erythematous papules, pustules, nodules and cysts of inflammatory acne [1, 5].

In very rare cases, however, the primary acne lesions occur together with a wooden, solid facial edema (SFE). Typically, the acne lesions are moderate to severe but in no way extreme, hence this phenomenon cannot be explained by simple edema due to inflammation. It was first observed and published by Connelly and Winkelmann in 1985 [6]. Although we believe we have understood more about acne pathogenesis since then, solid facial edema remains a mystery. It has been suggested that chronic inflammation, comparable to other body regions such as the legs, damages the lymphatic system and leads to fibrosis, which is further supported by mast cells. Accordingly, early treatment before damage is irreversible seems sensible. Here, we report two Swiss cases of SFE in acne vulgaris and summarize the clinical features and treatment responses of SFE cases in the literature.

Case Report

A 18-year old carpenter presented with numerous papules and pustules on the forehead and cheeks compatible with acne. Initially, he had been fruitlessly treated with topical retinoids. Instead, after 6 months of therapy, the patient developed a localized, symmetric, wooden, non-pitting edema over the cheeks and infraorbital regions, the lower front and glabella. All edematous areas were beset with multiple comedones and papulopustules (Fig. 1). A punch biopsy revealed some dermal edema and fibrosis as well as moderate infiltrates composed of lymphocytes and neutrophils granulocytes around the pilo-sebaceous unit (Fig. 2). Treatment with 2 mg/kg oral prednisone for 12 days in combination with 20 mg isotretinoin for 2 months resulted in a complete regression of the edema.

Fig. 1
figure 1

Diffuse papules and pustules with facial wooden edema in the periorbital area

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Fig. 2
figure 2

Biopsy of case 1 revealing dermal edema and fibrosis as well as mixed cellular infiltrate around the pilo-sebaceous unit

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The second case was an otherwise healthy 20-year-old student, who consulted for a persisting edematous reaction of the left upper and lower eyelid and cheek that had developed 5 months earlier. It had started during treatment with topical retinoids for erythematous papules and pustules interpreted as acne vulgaris that had arisen on the forehead, cheeks, chin and pre-sternal area. Shortly after commencing the treatment, the indurated edema developed. No comedones nor teleangiectasias were present. A biopsy showed a spongiotic dermatitis, probably due to local treatment, as well as acne of a typical mixed cellular and mixed perifollicular inflammation. Further, fibrosis in the middle and dermis was quite prominent. After 8 months treatment with isotretinoin 20 mg per day and an antihistamine, the facial edema slowly cleared.

Compliance with Ethics Guidelines

Informed consent was obtained from the patients prior to publication.

Discussion

A total of 20 similar cases have been reported so far in the medical literature (Table 1). Multiple strategies were used in attempts to treat the edema. The first therapy attempt, with elastic facial stockings for several months as reported by Connelly and Winkelmann, failed [6]. In 8 cases, 0.5–1 mg/kg per day isotretinoin was reported as an effective treatment of the facial edema in acne vulgaris [7,8,9,10]. There were two reported cases of treatment failure after 3 and 4 months of therapy with isotretinoin, which corresponds with our experience, as in the second case, we observed improvement only after 8 months of treatment [11, 12]. Therapy attempts with oral prednisone alone showed no improvement of the facial edema, in contrast to successes by a combination with isotretinoin [13]. Surgical therapy after failure of conventional treatment, as reported in one case, led to complete resolution [14]. It remains unknown whether the result was aesthetically satisfying. In the related condition called Morbihan disease, isotretinoin monotherapy and combination therapies of isotretinoin with either ketotifen or clofazimine all produced good results [12, 15].

Table 1 Cases of SFE reported in the literature
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These two cases illustrate this typical, almost unmistakable, disease of solid facial edema which produces a striking facies. This condition does not stand alone—clinically closely comparable to the initial report of Connelly and Winkelmann [6], quite similar reports of SFE as a rare complication of rosacea (Morbihan disease) were published in 1957 [15]. Morbihan disease also produces solid facial edema with histopathologic features of granulomatous rosacea that can occur at any stage of the disease [15]. The pathogenesis of Morbihan disease also remains unclear [15, 16], the two main hypotheses being lymph vessel abnormalities or the edema representing an inflammatory effect [12, 15]. This peculiar edema is not reduced when standing, nor does it show variation during the day. Interestingly, a number of other facial dermatoses can produce similar effects, including dermatomyositis, angiedema, Melkersson–Rosenthal and Heerfordt’s syndrome [17,18,19].

We believe a common inflammatory pattern may be underlying all these conditions. A number of mediators are directly involved in induction of edema, including bradykinin, interleukin 1 beta, histamine and others. These are produced by cells both of the innate (mast cells, granulocytes, monocytes/macrophages) as well as of the adaptive immune system (T cells). We have therefore undertaken comparative studies that are currently ongoing. Once the pathogenesis of persisting edema is better understood, more targeted and effective therapies might be within our reach.