Intralymphatic Histiocytosis Treated With Intralesional Triamcinolone Acetonide and Pressure Bandage

Comment

Intralymphatic histiocytosis is a rare cutaneous disorder defined histologically by histiocytes within the lumina of lymphatics. In addition to the current case, our review of PubMed articles indexed for MEDLINE using the search term intralymphatic histiocytosis yielded more than 70 total cases. The condition has a slight female predominance and typically is seen in individuals over the age of 60 years (age range, 16–89 years).¹² Many cases are associated with RA/elevated rheumatoid factor.^2,4,8,15-30 At least 9 cases of intralymphatic histiocytosis were associated with premalignant or malignant conditions (ie, adenocarcinoma of the breasts, lungs, and colon; Merkel cell carcinoma; melanoma; melanoma in situ; Mullerian carcinoma, gammopathy).^4,15,31-34 Primary disease, defined as occurring in patients who are otherwise healthy, was noted in at least 10 cases.^{1,2,4,12,35,36} Finally, intralymphatic histiocytosis was identified in areas adjacent to metal implants and joint replacements or exploration in approximately 15 cases (including the current case).^3-14,29,37

The condition presents with papules, plaques, and nodules in the setting of characteristic livedoid discoloration; however, some patients present with nonspecific nodules or plaques. Lesions may be symptomatic (eg, pruritic, tender) or asymptomatic. The histologic features of intralymphatic histiocytosis are distinctive but may be focal, as in our case, and the diagnosis is easily missed. The histologic differential diagnosis includes diseases in which intravascular accumulations of cells may be seen, including intravascular B-cell lymphoma, which can be excluded with stains that detect B cells (CD20/CD79a), and reactive angioendotheliomatosis, a benign proliferation of endothelial cells, which may be excluded with stains against endothelial markers (CD31/CD34). The course typically is chronic, and treatment with topical steroids,^3,9,15,22,26 cyclophosphamide,¹⁵ local radiation,¹ thalidomide,³⁵ pentoxifylline,⁷ and RA medications (eg, prednisolone, methotrexate, nonsteroidal anti-inflammatory drugs, hydroxychloroquine) generally are ineffective.^2,16,20,25 Symptoms may improve with joint replacement,⁴ excision of the involved lesion, treatment of an associated malignancy/infection,^33,36,38,39 nonsteroidal anti-inflammatory drugs, intra-articular steroid injection,¹⁸ amoxicillin and aspirin,¹⁹ infliximab,²⁵ pressure bandage application,²⁶ steroid-containing adhesive application,¹⁸ arthrocentesis,^3,27 oral pentoxifylline,²¹ tacrolimus,²⁹ CO₂ laser,⁴⁰ prednisolone,⁴¹ and tocilizumab.²⁸ Treatment of associated RA is beneficial in rare cases.^{2,15,20,25,26}

The pathogenesis of intralymphatic histiocytosis has not been elucidated with certainty but may represent an abnormal proliferative response of histiocytes and vessels in response to chronic systemic or local inflammation. Lymphangiectasis caused by lymphatic obstruction secondary to trauma, surgical manipulation, or chronic inflammation can promote lymphostasis and slowed clearance of antigens producing an accumulation of histiocytes and subsequent local immunologic reactions, thus an “immunocompromised district” is formed.⁴² It also is thought that rheumatic or prosthetic joints produce inflammatory mediator–rich (namely tumor necrosis factor α) synovial fluid that drains and collects within the dilated lymphatics, creating a nidus for histiocytes.^1,5 In one case, treatment with an anti–tumor necrosis factor antibody (infliximab) improved the skin presentation and rheumatoid joint pain.²⁵ Bakr et al² noted an association with increased intralymphatic macrophage HLA-DR expression. This T-cell surface receptor typically is upregulated in cases of chronic antigen stimulation and autoimmune conditions.

Conclusion

Our patient had a history of a joint prosthesis and a popliteal cyst, which could have altered lymphatic drainage promoting abnormal immune cell trafficking contributing to the development of intralymphatic histiocytosis. The response to intralesional steroids supports this pathogenic hypothesis. Specifically, direct injection of the area suppressed the immune dysregulation, while compression lessened the degree of lymphostasis. In light of previously reported cases of intralymphatic histiocytosis in association with metal implants,^3-9 we suggest that the condition should be considered in patients with chronic painful livedoid nodules or plaques around an affected joint, even in the absence of RA. The dermatopathologist should be warned to search carefully for the subtle but distinctive histologic features of the disease that confirm the diagnosis. Treatment with intralesional triamcinolone acetonide with an overlying pressure wrap has minimal side effects and can work quickly with sustained benefits.