Rosai-Dorfman disease (RDD) is very rare and exists in two main forms: One form that affects lymph nodes (sinus histiocytosis with massive lymphadenopathy) and rarely extranodal organs, and the other form that is purely cutaneous without systemic or nodal disease. The cutaneous form of RDD is rare and generally self limited. It presents as one or several deep red papules, plaques, or deep nodules that enlarge, persist, or regress and disappear over time. Skin lesions may deeply infiltrate into tissue and cause functional or aesthetic problems to the patient. Characteristic features on skin biopsy include the presence of a mixed superficial and deep inflammatory infiltrate with sheets of large S-100 positive histiocytes and emperipolesis, a process in which leukocytes transmigrate through the histiocyte. Based on case reports and anecdotes, some treatment options have been suggested for patients with persistent or symptomatic disease, with varying efficacy. The authors present a single patient in order to add their experience with acitretin treatment to the literature.
A healthy 82-year-old woman developed a dark red, painless plaque on the right upper extremity over a few months without any associated symptoms or lymphadenopathy (). It had not changed in size over two months, despite treatment with antibiotics and oral glucocorticoids. She had no signs or symptoms of systemic disease and her complete blood count (CBC) was within normal limits.
Photograph of cutaneous Rosai-Dorfman disease on the patient’s upper extremity, following excision of the subcutaneous mass, taken before (A) and four months after discontinuing treatment with acitretin (B).
A magnetic resonance imaging (MRI) of the arm, neck, and chest showed edema in the subcutaneous fat and skin overlying the distal deltoid muscle, without lymph node enlargement. Excisional biopsy of the mass revealed a sheet-like proliferation of large, foamy histiocytes with emperipolesis and a pronounced mixed chronic inflammatory cell infiltrate. The histiocytes were S-100 positive by immunohistochemistry and a diagnosis of cutaneous Rosai-Dorfman was made.
She underwent complete excision of the lesion; however, local regrowth was noted over the next 6 to 7 months. A second incisional skin biopsy confirmed the diagnosis of localized cutaneous Rosai-Dorfman disease (CRDD) (). After surgical treatment failed, the authors sought medical treatment options and found one case report of CRDD treated successfully with acitretin.1
The patient was started on acitretin 10mg orally per day with ongoing monitoring of fasting lipids, CBC, and liver function tests. After one month of treatment with slight improvement, the dose was increased to 25mg daily.
Figure 2 Hematoxylin and eosin stain of incisional biopsy taken around the same time as . The asterisk (*) indicates a foamy histiocyte with emperipolesis of lymphocytes in the background of a mixed infiltrate of lymphocytes, plasma cells, histiocytes, (more ...)
Over the next three months, there was further resolution of the lesion (). On follow-up exam, there was a significant decrease in plaque firmness and reduction of erythema and induration of the subcutaneous tissue. However, four months into treatment, the patient experienced hair loss and dry skin and she chose to discontinue treatment.
Sinus histiocytosis with massive lymphadenopathy, or RDD, is a rare, benign, self-limiting disorder of unknown etiology. It exists in an indolent cutaneous form without systemic symptoms and, a nodal form, which is characterized by massive lymphadenopathy, frequently affecting the cervical lymph nodes with or without systemic symptoms of fever and leukocytosis. Both forms typically follow a benign course and resolve spontaneously. Periodic exacerbations may occur.2,3
The purely cutaneous form of the disease, as in our patient, is very rare.3
While classic RDD is more commonly seen in young adult males, those with CRDD are typically female and older.1,3
CRDD presents as erythematous to brown papules, plaques, or nodules. There is no predilection for site and patients with CRDD are free from systemic manifestations.3
The rarity of CRDD makes randomized clinical treatment trials or large case series impossible and most of our knowledge about treatment is based on single case reports. Various treatments have been described for CRDD. Due to its benign course and spontaneous resolution in most cases, it is suggested that less aggressive options are employed when possible. Though many treatments have been described, no single option is successful in all cases. Surgical excision of the lesions has been shown to be effective in many cases.4,5
Improvement has also been observed with topical and systemic steroids,6–8
cryotherapy, local radiation,9
Treatment with dapsone resulted in improvement in a patient refractory to steroids.10
Similarly, thalidomide has also been effective in patients refractory to other treatments.4,11
Mixed results have been seen with isotretinoin.4,12,13
Though imatinib mesylate was effective in a case of systemic RDD,14
it was ineffective in treating CRDD.15
The authors’ patient had been treated with oral glucocorticoids without improvement, followed by surgical excision of her bulky subcutaneous disease. After excision, her localized cutaneous disease persisted. The authors treated the patient’s residual disease with acitretin, with significant improvement. Unfortunately, the patient decided to discontinue treatment due to medication side effects, making it impossible to assess whether complete resolution could have been achieved with this regimen. To the authors’ knowledge, there has been only one previous report1
on the potential effectiveness of acitretin treating CRDD. Acitretin is relatively safe when compared to other treatments and is useful for cutaneous involvement.
Though CRDD is benign and self limited in most patients, it does persist in some patients and may become symptomatic in skin overlying joints or in cosmetically sensitive areas. This case corroborates the only report to date of acitretin in the treatment of CRDD.