Microscopic study of cutaneous lesions in early HS lesions shows several histopathological findings, including hyperkeratinization of the follicular infundibulum, follicular plugging, dilated hair follicles, cyst formation, and a massive inflammatory neutrophil infiltration. Multinucleated giant cells, monocytes, macrophages, and dendritic cells are also increased. In addition, the epidermis usually displays psoriasiform hyperplasia, which can also be observed in normal-appearing perilesional skin and in chronic lesions. One of the hallmarks of cutaneous lesions in HS is the development of epithelialized fistulas that are exclusive to chronic lesions. The number of lymphocytes, tryptase-positive mast cells, and especially CD20+ and CD79+ B cells and CD138+ plasma cells are increased.1
It has been suggested that elevated IL-10 levels in these patients could promote B-cell differentiation into plasma cells. The presence of this infiltrate composed of plasma cells may be associated with the presence of a polyclonal increase in immunoglobulins A, G, and E that has been detected in the serum of patients with HS.2,3
To the best of our knowledge, the presence of crystal deposition in HS lesions has not been reported in the English literature. These structures have, however, been described in cutaneous conditions associated with underlying plasma cell dyscrasias, including crystalglobulinemia, type 1 cryoglobulinemia, and crystal-storing histiocytosis, as well as in a case of Rosai–Dorfman disease.
Crystalglobulinemia is a rare, occlusive vascular condition associated with multiple myeloma, causing necrotic skin lesions and kidney damage. Crystals are composed of monoclonal immunoglobulins and are positive with immunohistochemical staining for immunoglobulins and also with the periodic acid-Schiff stain. Crystals are eosinophilic, elongated, and rectangular shaped. They usually affect glomeruli, arterioles, and the Bowman capsule, although they have also been reported in cutaneous lesions within dermal vessels.4
Monoclonal or type 1 cryoglobulinemia may be idiopathic or associated with myeloma or lymphoproliferative disorders. The most frequent histopathological finding is the lumina of small blood vessels filled with a homogeneous, eosinophilic material containing a cryoprecipitate of immunoglobulins. Type 1 cryoglobulinemia rarely manifests as cutaneous small vessel vasculitis. Intravascular crystal formation in the setting of cutaneous small vessel vasculitis in type 1 cryoglobulinemia has been reported in a patient with a monoclonal gammopathy of undetermined significance.5
The presence of cutaneous crystalline deposits in myeloma has also been reported in other cutaneous presentations, including crystal-storing histiocytosis. Crystal-storing histiocytosis occurs less frequently in other lymphoproliferative disorders and also in rare reactive conditions. Crystals are also composed of light chains of immunoglobulins or paraproteins. These are present within histiocytes, more frequently not only in the bone marrow but also in extramedullary locations, including the skin.6,7
Finally, a case of cutaneous Rosai–Dorfman disease has been reported in which the presence of rhomboid and needle-shaped crystals was detected both extracellularly and in the cytoplasm of histiocytes. Nevertheless, crystals did not stain with either light chain immunochemistry or amyloid stains. In this case, crystals appeared in a massive infiltrate with numerous activated plasma cells and prominent Russell bodies, as in our patient.6
Several theories have been proposed to explain the formation of crystals, including immunoglobulin overproduction, alterations in immunoglobulin secretion, failure in the degradation of immunoglobulins, and production of a defective structural protein that predisposes to crystal formation.6 Herein, we report what, to our knowledge, is the first case of HS with crystal formation.
In summary, immunoglobulin crystal formation in the skin may be detected in cutaneous conditions related to underlying plasma cell dyscrasias, as occurs in crystalglobulinemia, type 1 cryoglobulinemia and crystal-storing histiocytosis, or in cutaneous diseases with an abundance of plasma cells, such as in the case reported of cutaneous Rosai–Dorfman disease or in the current case. Our patient presented with increased levels of polyclonal IgG, although polyclonal hyperglobulinemia in patients with HS has been reported previously.3 In view of the relationship between plasma-rich infiltrate conditions and the development of crystals, we believe that the presence of crystals represents a secondary phenomenon to the prominent number of reactive plasma cells in the infiltrate of cutaneous lesions of HS.
1. van der Zee HH, de Ruiter L, Boer J, et al. Alterations in leucocyte subsets and histomorphology in normal-appearing perilesional skin and early and chronic hidradenitis suppurativa lesions. Br J Dermatol. 2012;166:98–106.
2. Pascual JC, García-Martínez FJ, Martorell A, et al. Increased total serum immunoglobulin E levels in moderate to severe hidradenitis suppurativa. Br J Dermatol. 2016;175:1101–1102.
3. Hoffman LK, Ghias M, Cohen SR, et al. Polyclonal hyperglobulinemia and elevated acute phase reactants in hidradenitis suppurativa. Br J Dermatol. 2017 [epub ahead of print].
4. Llamas-Velasco M, Alegría V, Santos-Briz Á, et al. Occlusive nonvasculitic vasculopathy. Am J Dermatopathol. 2017;39:637–662.
5. Gammon B, Longmire M, DeClerck B. Intravascular crystal deposition: an early clue to the diagnosis of type 1 cryoglobulinemic vasculitis. Am J Dermatopathol. 2014;36:751–755.
6. Motta L, McMenamin ME, Thomas MA, et al. Crystal deposition in a case of cutaneous Rosai-Dorfman disease. Am J Dermatopathol. 2005;27:339–342.
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7. Jenkins RE, Calonje E, Fawcett H, et al. Cutaneous crystalline deposits in myeloma. Arch Dermatol. 1994;130:484–488.