Case Report
A 63-year-old woman had a 6-month history of malaise, fever, and weight loss. Diabetes
mellitus type II was diagnosed 16 years ago. Clinical examination showed symmetrical
violaceous indurated patches on the skin of her earlobes, elbows, knees, and upper
arms ([Fig. 1 a – c]). Based on clinical findings and positive Borrelia burgdorferi IgG antibodies, a diagnosis of an inflammatory-edematous stage of Acrodermatitis
chronica atrophicans could not be excluded. The patient was treated with Ceftriaxone
2 g/day for 5 days and Cefuroxime 1 g/day for 3 weeks. Skin lesions reduced, malaise
and fever remained. Laboratory findings showed anemia, leukopenia, thrombocytopenia,
elevated amounts of liver enzymes GGT 389 IU/L; alkaline phosphatase 162 UI/L; CRP
39 mg/l, ESR 37 mm/h. Blood and urine cultures, immunological laboratory findings
of systemic connective tissue diseases were negative. A biopsy of skin lesions was
performed. Dermatohistopathology revealed vascular proliferation with dilated clusters
of dermal capillaries partly occluded by cellular thrombi and large multiple hematopoietic
intravascular cells positive for LCA and negative for CD31, CD34, CD3, CD20, CD1a
and S100 markers. The positivity of CD68 markers suggested a histiocytic origin of
intravascular cells. D2-40 marker highlighted lymphatic vessels with no histiocytes
inside ([Fig. 2 – 7]). Clinical and histological findings led to a diagnosis of cutaneous intravascular
histiocytosis. Abdominal ultrasound investigation showed dysmetabolic, enlarged liver
and splenomegaly. Liver biopsy indicated reactive changes and periportal steatosis
of hepatocytes. Transoesophageal heart sonography supported a diagnosis of infectious
endocarditis which was verified after heart valve replacement surgery.
Fig. 1 Clinical view: Symmetrical violaceous skin patches on knees (a), earlobes (b) and elbows (c).
Fig. 2 H + Ex100: Dermal vascular proliferation, large cells with oblong basophilic nuclei.
Fig. 3 LCA positive intravascular cells.
Fig. 4 CD68 positive intravascular cells.
Fig. 5 D2-40 marker highlights lymphatic vessels with no histiocytes inside.
Fig. 6 CD31 negative cells.
Fig. 7 CD34 negative cells.
After treatment with Benzylpenicillin at 18.000.000 Units/day intravenously for 21
days skin lesions, fever and malaise improved. Heart valve replacement surgery was
performed due to chronic active infectious endocarditis.
Discussion
Intravascular histiocytosis (IVH) is a rare benign cutaneous disorder of unknown pathogenesis,
characterized by a reactive intravascular dermal proliferation of histiocytes. This
rare disease was firstly described in 1994 and named intravascular histiocytosis by
O’Grady et al. [1]. Some authors described this condition as early stage of reactive angioendotheliomatosis
(RAE) [2]
[3]. Subsequent authors proved the lymphatic nature of the ectatic vessels by demonstrating
the expression of a lymphatic endothelial cell marker, podoplanin (D2-40). The condition
has since been referred to as intralymphatic histiocytosis
[4].
Bakr et al. report a total of 46 cases of IVH [4]. Most cases arise in patients with rheumatoid arthritis (RA) [4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13], tonsillitis [14], rheumatic fever [2], orthopedic metal implants [15], trombogenic diathesis and vulvar necrosis [16], colon carcinoma [8]
[17], tuberculosis [17]. Some publications [2]
[3] refer that IVH can be associated with infectious endocarditis, but we could not
find any properly documented cases reported in scientific data bases.
The origin of this condition remains unclear. Requena et al. suggest chronic inflammation
and the drainage of inflammatory mediators away from the synovium into lymphatic vessels
by RA [5]. Okamoto et al. highlighted the potential role of tumor necrosis factor-alfa, an
important mediator of inflammation in RA, which could potentially leak from inflamed
joints causing the intralymphatic aggregation of macrophages. In support of this hypothesis,
blockade of antitumor necrosis factor-alfa using infliximab has been shown to markedly
improve the skin lesions of IVH [6]. Further, IVH has been observed to regress after treatment of associated conditions
[4].
In contrast to most reported cases of IVH, our patient had no clinical history or
symptoms to suggest an associated rheumatoid arthritis. Also the dilated vessels with
histiocytes were negative for monoclonal antibody D2-40.
The clinical presentation of IVH is characterized by poorly defined erythematous plaques,
mainly on the limbs, sometimes in association with livedo reticularis or superficial
papules, vesicles, or nodules [1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17].
Histopathologically, IVH is characterized by the proliferation of histiocytes in the
dilated blood or lymphatic vessels [1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]. Histologic differential diagnosis should include angiosarcoma, malignant and reactive
angioendotheliomatoses, intravascular lymphoma, Langerhans‘ cell histiocytosis. In
our case CD31, CD34 markers, which highlight endothelial cells, were negative. Thus
angiosarcoma, malignant and reactive angioendotheliomatoses were excluded. We ruled
out lymphomas according to negative markers for CD3 and CD20, CD1a and S100. Negative
intravascular cells do not fit for Langerhans’ histiocytosis.
IVH is a rare reactive cutaneous lesion of unknown pathogenesis. Treatment of IVH
is usually directed towards associated systemic illnesses. The diagnosis of IVH is
important and may necessitate further clinical evaluation to exclude the possibility
of co-existing autoimmune and infectious systemic disease.
