The assertion by some, that the histiocytoid cells are in fact a manifestation of leukemia cutis, has sparked significant debate since Requena and colleagues’ original report. As leukemia cutis heralds death within 1 year for 88% of patients with AML and CML, the origin of these cells is critical.78,79 The infiltrate in leukemia cutis can be histopathologically indistinguishable from the aforedescribed infiltrate in histiocytoid Sweet syndrome, making this determination difficult.80 Requena and colleagues note that peripheral blood smears in 27 of their patients with histiocytoid Sweet syndrome did not demonstrate circulating leukemic cells, and the bcr/abl fusion gene was not identified by fluorescent in situ hybridization (FISH) in the dermal infiltrate. In addition, clinical follow-up over several years did not eventuate in any acute or chronic myelogenous leukemia. Thus, Requena and colleagues assert in their original publication that the histiocytoid cells are not leukemic and, furthermore, are not seen in association with underlying hematologic abnormalities in any higher frequency than classic Sweet Syndrome; 24% of their cases of histiocytoid Sweet syndrome were associated with an underlying hematologic dyscrasia, whereas 21% of classic Sweet syndrome are associated with any type of underlying malignancy.81
While the association with underlying hematologic malignancy remains controversial, a novel immunohistochemical marker to distinguish the infiltrates in histiocytoid Sweet syndrome and leukemia cutis may bring clarity to the histopathologic diagnosis and its clinical implications. Previous attempts to identify leukemic cells in the skin with blast markers CD34 and CD117 have been challenging, as these markers are often negative in leukemia cutis. Missense mutations in erythroblast transformation-specific regulated gene-1 (ERG), a regulator of cell proliferation, differentiation, angiogenesis, and apoptosis, have been reported in a subset of patients with AML and subsequently in patients with a variety of leukemias.87,88 Xu et al89 recently report that ERG is a strong and specific immunomarker for leukemia cutis, with a sensitivity of 81.4% and specificity of 100%, based on a cohort of 32 patients, 16 with known leukemia cutis (with bone marrow biopsy-proven malignancy) and 16 with reactive myeloid infiltrates (a broad category of inflammatory disorders that included Sweet syndrome but also other reactive dermatitides). Given the potentially similar appearance of the infiltrates in histiocytoid Sweet syndrome and leukemia cutis, and the extremely different prognosis of the 2 conditions, a reliable immunohistochemical marker such as ERG may be of value.
The “neutrophilic dermatoses of lupus erythematosus,” and the prior reported cases of “Sweet-like syndrome” of LE, fit into a larger category of neutrophilic dermatoses that are observed in the setting of a variety of autoimmune connective tissue diseases (AICTDs), including rheumatoid arthritis, Sjögren syndrome, and Still disease.95 It is now widely accepted that neutrophil-rich dermatoses resembling SS, with a neutrophil-rich infiltrate, leukocytoclasia and lack of primary vasculitis may occur in the setting of a variety of AICTDs, and “autoimmune neutrophilic dermatosis” is an appropriate description for the entity.96 Distinguishing the 2 patterns is essential to arrive at the correct diagnosis (Table 1).
The role of neutrophils in autoimmune and autoinflammatory diseases has long been overlooked, with the emphasis instead being on autoreactive T lymphocytes that develop after an “immunization” phase, and then activate a variety of cell types that damage host tissue (“effector” phase). However, neutrophils are capable of contributing to autoimmunity, both in the “immunization” phase by exposing autoantigens when involved in a vasculitic process, during apoptosis, or as mediators of cell damage in the “effector” phase.99,100 In lesional skin of neutrophilic dermatoses, cytokines that recruit neutrophils and amplify the inflammatory response are known to be overexpressed.101 In addition, aberrant expression and/or activation of adhesion and migration molecules that assist in neutrophil migration to local tissues (such as intercellular adhesion molecule-1) has been observed in the eruption of dermatomyositis.102 The specific mechanism of the neutrophilic dermatoses in AICTD is poorly understood, but neutrophils appear to play a role in pathogenesis.
It is essential for pathologists to recognize the role of neutrophils in the spectrum of cutaneous manifestations of hematologic dyscrasias and connective tissue disorders and be familiar with the histologic features.
Calcification of the arteriole media is the result of downstream effects of dysregulation of systemic mineralization leading to an imbalance of procalcification and anticalcification factors in both the circulation and local tissue environment. Elevations in circulating calcium-phosphate product (CaXP) and upregulation of procalcifying products in the extracellular matrix occur in the setting of decreased levels of anticalcification products, namely Fetuin-A and matrix gla protein, found in the systemic circulation and extracellular matrix, respectively.94,96 As a result of this procalcification milieu and the presence of various osteogenic factors, such as bone morphogenic protein-4 and osteopontin, vascular smooth muscle cells transform from a contractile phenotype to an osteoblast-like phenotype that results in calcification of the smooth muscle of the arteriole media.105,107 Transformed vascular smooth muscle cells not only promote calcification, but may also trigger intimal hyperplasia and vascular sloughing resulting in nonthrombotic vascular occlusion.107
Thrombotic occlusion and hypercoagulability are also gaining appreciation for their role in the development in calciphylaxis lesions. Systemic hypercoagulability, including protein C and S deficiencies have been reported in cases of calciphylaxis, and it is also believed that inflammatory cytokines and reactive oxygen species, triggered by vascular injury, may induce a local hypercoagulable reaction with subsequent areas of focal thrombosis and necrosis. It is this appreciation of an underlying prothrombotic state that helps to explain cases of calciphylaxis in nonuremic patients.105,106
Chen and colleagues recently demonstrated that a skin biopsy can be especially useful in patients with end-stage chronic kidney disease (CKD), as significant histologic differences have been demonstrated in CKD patients with and without calciphylaxis. The authors found that CKD patients with calciphylaxis were significantly more likely to demonstrate thrombi and vessel wall calcification in the dermis and superficial fat, thrombi within calcified vessels, and dermal angioplasia compared with CKD patients without calciphylaxis. The authors also demonstrated that there were no significant histopathologic changes in calciphylaxis patients with and without renal disease.110
Calcification of extravascular structures, such as dermal collagen and subcutaneous fat are helpful histologic features, but its specificity is attenuated by conditions that can demonstrate similar features, such as lupus and pancreatic panniculitides.108 Perieccrine calcification (Fig. 16), however, is one form of extravascular calcification that is a subtle, but potentially valuable feature. In a retrospective case-control study by Mochel et al,108 perieccrine calcification, detectable only with von Kossa and Alizarin red calcium stains, was found to be highly specific, having been identified in 11% (n=6/55) of cases and no controls. Notably, perieccrine calcification was the only form of calcium deposition identified in 4 of the 6 cases. While this finding was not statistically significant (P=0.33) likely due to the small sample size, it is potentially instrumental in histologically challenging cases. Since this study was published, perieccrine calcification in calciphylaxis has been addressed in 2 publications. A case report by Dookhan et al114 confirmed the presence of this feature in a 44-year-old male with uremic calciphylaxis. Similar to the aforementioned case-control study, perieccrine calcification was not identifiable with hematoxylin and eosin staining and was only visualized with von Kossa calcium staining. A retrospective case-control study by Chen and colleagues did not identify perieccrine calcification in any of their 57 calciphylaxis subjects; however, calcium stains were not utilized in the analysis of these histologic specimens.11
Cutaneous PXE-like histopathologic features in the absence of systemic involvement have been described in association with various autoimmune and metabolic disorders,119–128 in addition to 3 case reports and 2 case series of uremic and nonuremic calciphylaxis.104,129–132 These cases demonstrate histologic features of calciphylaxis in conjunction with the curled, frayed and calcified elastic fibers known to PXE, which can be localized to either the reticular dermis or septae of the subcutaneous fat (Fig. 18).104,129–132 This finding is identifiable with hematoxylin and eosin staining, but may be better visualized with special calcium stains (ie, von Kossa) and elastic fiber stains (ie, Verhoeff-Van Gieson stain). The mechanism for the development of PXE-like features in calciphylaxis is unclear, but given the frequent difficulty in demonstrating vascular calcium deposition, it has been proposed as a feature that may heighten suspicion for an underlying diagnosis of calciphylaxis in the appropriate clinical setting.
In conclusion, inflammatory dermatopathology is an evolving field, with an ever-changing landscape. Changing trends in infectious diseases, medication advances, and refined characterization of various dermatologic conditions have accounted for recent updates within the field. This complex subject demands a high index of suspicion, and vigilance to maintaining up to date knowledge of dermatology to ensure an accurate diagnosis.
. 2017. Available at: cdc.gov
2. Peeling RW, Mabey D, Kamb ML, et al. Syphilis
. Nat Rev Dis Primers. 2017;3:17073.
3. Weedon D. Skin Pathology, 2nd ed. London: Churchill-Livingstone; 1998.
4. Flamm A, Parikh K, Xie Q, et al. Histologic features of secondary syphilis
: a multicenter retrospective review. J Am Acad Dermatol. 2015;73:1025–1030.
5. Tse JY, Chan MP, Ferry JA, et al. Syphilis
of the aerodigestive tract. Am J Surg Pathol. 2017;42:472–478.
6. Martin-Ezquerra G, Fernandez-Casado A, Barco D, et al. Treponema pallidum
distribution patterns in mucocutaneous lesions of primary and secondary syphilis
: an immunohistochemical and ultrastructural study. Hum Pathol. 2009;40:624–630.
7. Ruiz SJ, Procop GW. Cross-reactivity of anti-Treponema immunohistochemistry with non-Treponema spirochetes
: a simple call for caution. Arch Pathol Lab Med. 2016;140:1021–1022.
8. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–723.
9. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–330.
10. Massari F, Santoni M, Ciccarese C, et al. PD-1 blockade therapy in renal cell carcinoma: current studies and future promises. Cancer Treat Rev. 2015;41:114–121.
11. McDermott DF, Drake CG, Sznol M, et al. Survival, durable response, and long-term safety in patients with previously treated advanced renal cell carcinoma receiving nivolumab. J Clin Oncol. 2015;33:2013–2020.
12. Gettinger SN, Horn L, Gandhi L, et al. Overall survival and long-term safety of nivolumab (anti-programmed death 1 antibody, BMS-936558, ONO-4538) in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol. 2015;33:2004–2012.
13. Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014;515:558–562.
14. Ciccarese C, Alfieri S, Santoni M, et al. New toxicity profile for novel immunotherapy agents: focus on immune-checkpoint inhibitors. Expert Opin Drug Metab Toxicol. 2016;12:57–75.
15. Sibaud V, Meyer N, Lamant L, et al. Dermatologic complications of anti-PD-1/PD-L1 immune checkpoint antibodies. Curr Opin Oncol. 2016;28:254–263.
16. Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol. 2002;3:611–618.
17. Wolchok JD, Weber JS, Hamid O, et al. Ipilimumab efficacy and safety in patients with advanced melanoma: a retrospective analysis of HLA subtype from four trials. Cancer Immun. 2010;10:9.
18. Lacouture ME, Wolchok JD, Yosipovitch G, et al. Ipilimumab in patients with cancer and the management of dermatologic adverse events. J Am Acad Dermatol. 2014;71:161–169.
19. Curry JL, Torres-Cabala CA, Kim KB, et al. Dermatologic toxicities to targeted cancer therapy: shared clinical and histologic adverse skin reactions. Int J Dermatol. 2014;53:376–384.
20. Curry JL, Tetzlaff MT, Nagarajan P, et al. Diverse types of dermatologic toxicities from immune checkpoint blockade therapy. J Cutan Pathol. 2017;44:158–176.
21. Jaber SH, Cowen EW, Haworth LR, et al. Skin reactions in a subset of patients with stage IV melanoma treated with anti-cytotoxic T-lymphocyte antigen 4 monoclonal antibody as a single agent. Arch Dermatol. 2006;142:166–172.
22. Voskens CJ, Goldinger SM, Loquai C, et al. The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network. PLoS One. 2013;8:e53745.
23. Abdel-Rahman O, ElHalawani H, Fouad M. Risk of cutaneous toxicities in patients with solid tumors treated with immune checkpoint inhibitors
: a meta-analysis. Future Oncol. 2015;11:2471–2484.
24. Hwang SJ, Carlos G, Wakade D, et al. Ipilimumab-induced acute generalized exanthematous pustulosis in a patient with metastatic melanoma. Melanoma Res. 2016;26:417–420.
25. Gormley R, Wanat K, Elenitsas R, et al. Ipilimumab-associated Sweet syndrome
in a melanoma patient. J Am Acad Dermatol. 2014;71:e211–e213.
26. Kyllo RL, Parker MK, Rosman I, et al. Ipilimumab-associated Sweet syndrome
in a patient with high-risk melanoma. J Am Acad Dermatol. 2014;70:e85–e86.
27. Pintova S, Sidhu H, Friedlander PA, et al. Sweet’s syndrome in a patient with metastatic melanoma after ipilimumab therapy. Melanoma Res. 2013;23:498–501.
28. Rudolph BM, Staib F, Von Stebut E, et al. Neutrophilic disease of the skin and intestines after ipilimumab treatment for malignant melanoma-simultaneous occurrence of pyoderma gangrenosum and colitis. Eur J Dermatol. 2014;24:268–269.
29. Reule RB, North JP. Cutaneous and pulmonary sarcoidosis-like reaction associated with ipilimumab. J Am Acad Dermatol. 2013;69:e272–e273.
30. Mochel MC, Ming ME, Imadojemu S, et al. Cutaneous autoimmune effects in the setting of therapeutic immune checkpoint inhibition for metastatic melanoma. J Cutan Pathol. 2016;43:787–791.
31. Munoz J, Guillot B, Girard C, et al. First report of ipilimumab-induced Grover disease. Br J Dermatol. 2014;171:1236–1237.
32. Uemura M, Faisal F, Haymaker C, et al. A case report of Grover’s disease from immunotherapy-a skin toxicity induced by inhibition of CTLA-4 but not PD-1. J Immunother Cancer. 2016;4:55.
33. Sheik Ali S, Goddard AL, Luke JJ, et al. Drug-associated dermatomyositis following ipilimumab therapy: a novel immune-mediated adverse event associated with cytotoxic T-lymphocyte antigen 4 blockade. JAMA Dermatol. 2015;151:195–199.
34. Yamaguchi Y, Abe R, Haga N, et al. A case of drug-associated dermatomyositis following ipilimumab therapy. Eur J Dermatol. 2016;26:320–321.
35. Ribas A, Chesney JA, Gordon MS, et al. Safety profile and pharmacokinetic analyses of the anti-CTLA4 antibody tremelimumab administered as a one hour infusion. J Transl Med. 2012;10:236.
36. Ribas A, Kefford R, Marshall MA, et al. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol. 2013;31:616–622.
37. Belum VR, Benhuri B, Postow MA, et al. Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor. Eur J Cancer. 2016;60:12–25.
38. Minkis K, Garden BC, Wu S, et al. The risk of rash associated with ipilimumab in patients with cancer: a systematic review of the literature and meta-analysis. J Am Acad Dermatol. 2013;69:e121–e128.
39. Joseph RW, Cappel M, Goedjen B, et al. Lichenoid dermatitis in three patients with metastatic melanoma treated with anti-PD-1 therapy. Cancer Immunol Res. 2015;3:18–22.
40. Tetzlaff MT, Nagarajan P, Chon S, et al. Lichenoid dermatologic toxicity from immune checkpoint blockade therapy: a detailed examination of the clinicopathologic features. Am J Dermatopathol. 2017;39:121–129.
41. Sibaud V, Eid C, Belum VR, et al. Oral lichenoid reactions associated with anti-PD-1/PD-L1 therapies: clinicopathological findings. J Eur Acad Dermatol Venereol. 2017;31:e464–e469.
42. Sanlorenzo M, Vujic I, Daud A, et al. Cutaneous adverse events and their association with disease progression. JAMA Dermatol. 2015;151:1206–1212.
43. Freeman-Keller M, Kim Y, Cronin H, et al. Nivolumab in resected and unresectable metastatic melanoma: characteristics of immune-related adverse events and association with outcomes. Clin Cancer Res. 2016;22:886–894.
44. Hua C, Boussemart L, Mateus C, et al. Association of vitiligo with tumor response in patients with metastatic melanoma treated with pembrolizumab. JAMA Dermatol. 2016;152:45–51.
45. Rivera N, Boada A, Bielsa MI, et al. Hair repigmentation during immunotherapy treatment with an anti-programmed cell death 1 and anti-programmed cell death ligand 1 agent for lung cancer. JAMA Dermatol. 2017;153:1162–1165.
46. Totonchy MB, Ezaldein HH, Ko CJ, et al. Inverse psoriasiform eruption during pembrolizumab therapy for metastatic melanoma. JAMA Dermatol. 2016;152:590–592.
47. Ohtsuka M, Miura T, Mori T, et al. Occurrence of psoriasiform eruption during nivolumab therapy for primary oral mucosal melanoma. JAMA Dermatol. 2015;151:797–799.
48. Jour G, Glitza IC, Ellis RM, et al. Autoimmune dermatologic toxicities from immune checkpoint blockade with anti-PD-1 antibody therapy: a report on bullous skin eruptions. J Cutan Pathol. 2016;43:688–696.
49. Carlos G, Anforth R, Chou S, et al. A case of bullous pemphigoid in a patient with metastatic melanoma treated with pembrolizumab. Melanoma Res. 2015;25:265–268.
50. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23–34.
51. Postow MA, Chesney J, Pavlick AC, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372:2006–2017.
52. Hu JC, Sadeghi P, Pinter-Brown LC, et al. Cutaneous side effects of epidermal growth factor receptor inhibitors
: clinical presentation, pathogenesis, and management. J Am Acad Dermatol. 2007;56:317–326.
53. Abdel-Rahman O, Fouad M. Correlation of cetuximab-induced skin rash and outcomes of solid tumor patients treated cetuximab: a systematic review and meta-analysis. Crit Rev Oncol Hematol. 2015;93:127–135.
54. Cho Y-T, Chen K-L, Sheen Y-S, et al. Purpuric drug eruptions caused by epidermal growth factor receptor inhibitors
for non-small cell lung cancer. A clinicopathologic study of 32 cases. JAMA Dermatol. 2017;153:906–910.
55. Reyes-Habito CM, Roh EK. Cutaneous reactions to chemotherapeutic drugs and targeted therapy for cancer: Part II. Targeted therapy. J Am Acad Dermatol. 2014;71:217.e1–217.e11; quiz 227–228.
56. Manousaridis I, Mavridou S, Goerdt S, et al. Cutaneous side effects of inhibitors of the RAS/RAF/MEK/ERK signalling pathway and their management. J Eur Acad Dermatol Venereol. 2013;27:11–18.
57. Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364:2507–2516.
58. Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010;363:809–819.
59. Anforth R, Fernandez-Penas P, Long GV. Cutaneous toxicities of RAF inhibitors. Lancet Oncol. 2013;14:e11–e18.
60. Anforth RM, Blumetti TCMP, Kefford RF, et al. Cutaneous manifestations of dabrafenib GSK2118436): a selective inhibitor of mutant BRAF in patients with metastatic melanoma. Br J Dermatol. 2012;167:1153–1160.
61. Chu EY, Wanat KA, Miller CJ, et al. Diverse cutaneous side effects associated with BRAF inhibitor therapy: a clinicopathologic study. J Am Acad Dermatol. 2012;67:1265–1272.
62. Trefzer U, Minor D, Ribas A, et al. BREAK-2: a phase IIA trial of the selective BRAF kinase inhibitor GSK2118436 in patients with BRAF mutation-positive (V600E/K) metastatic melanoma. Pigment Cell Res. 2011;24:990–1075.
63. Zimmer L, Livingstone E, Hillen U, et al. Panniculitis with arthralgia in patients with melanoma treated with selective BRAF inhibitors and its management. Arch Dermatol. 2012;148:357–361.
64. Dummer R, Rinderknecht J, Goldinger SM. Ultraviolet A and photosensitivity during vemurafenib therapy. N Engl J Med. 2012;366:480–481.
65. DeYoung MB, MacConell L, Sarin V, et al. Encapsulation of exenatide in poly- (D, L-Lactide-Co-Glycolide) microspheres produced an investigational long-acting once-weekly formulation for type 2 diabetes. Diabetes Technol Ther. 2011;13:1145–1154.
66. Boysen NC. Eosinophil-rich granulomatous panniculitis caused by exenatide injection. J Cutan Pathol. 2014;41:63–65.
67. Shan S-J, Guo Y. Exenatide-induced eosinophilic sclerosing lipogranuloma at the injection site. Am J Dermatopathol. 2014;36:510–512.
68. Andres-Ramos I, Blanco-Barrios S, Fernandez-Lopez E, et al. Exenatide-induced eosinophil-rich granulomatous panniculitis: a novel case showing injected microspheres. Am J Dermatopathol. 2015;37:801–802.
69. Vidal CI, Chaudhry S, Burkemper NM. Exenatide-induced panniculitis: utility of the acid-fast stain to identify injected microspheres. Am J Dermatopathol. 2017. [Epub ahead of print].
70. Sweet RD. Acute febrile neutrophilic dermatosis. Br J Dermatol. 1964;76:349–356.
71. Chan HL, Lee YS, Kuo TT. Sweet’s syndrome: clinicopathologic study in eleven cases. Int J Dermatol. 1994;33:425–432.
72. Eduardo Calonje J, Brenn T, Lazar A, et al. McKee’s Pathology of the Skin: with clinical correlations. Edinburgh: Elsevier/Saunders; 2012.
73. Requena L, Kutzner H, Palmedo G, et al. Histiocytoid Sweet syndrome
: a dermal infiltrate of immature neutrophilic granulocytes. Arch Dermatol. 2005;141:834–842.
74. Jordaan HF. Acute febrile neutrophilic dermatosis: a histopathological study of 37 patients and a review of the literature. Am J Dermatopathol. 1989;11:99–111.
75. Deguchi M, Tsunoda T, Yuda F, et al. Sweet’s syndrome in acute myelogenous leukemia showing dermal infiltration of leukemic cells. Dermatology. 1997;194:182–184.
76. Wong KF, Chan JKC. Antimyeloperoxidase: antibody of choice for labeling myeloid cells including diagnosis of granulocytic sarcoma. Adv Anat Pathol. 1995;2:65–68.
77. Pinkus GS, Pinkus JL. Myeloperoxidase: a specific marker for myeloid cells in paraffin sections. Mod Pathol. 1991;4:733–741.
78. Cho-Vega JH, Medeiros LJ, Prieto VG, et al. Leukemia cutis. Am J Clin Pathol. 2008;129:130–142.
79. Su WP, Buechner SA, Li CY. Clinicopathologic correlations in leukemia cutis. J Am Acad Dermatol. 1984;11:121–128.
80. Kaddu S, Zenahlik P, Beham-Schmid C, et al. Specific cutaneous infiltrates in patients with myelogenous leukemia: a clinicopathologic study of 26 patients with assessment of diagnostic criteria. J Am Acad Dermatol. 1999;40:966–978.
81. Cohen PR. Sweet’s syndrome—a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007;2:34.
82. Alegría-Landa V, Rodríguez-Pinilla SM, Santos-Briz A, et al. Clincopathologic, immunohistochemical, and molecular features of histiocytoid Sweet syndrome
. JAMA Dermatol. 2017;153:651–659.
83. Vignon-Pennamen MD, Osio A, Battistella M. Histiocytoid Sweet Syndrome
and Myelodysplastic Syndrome. JAMA Dermatol. 2017;153:835–836.
84. Osio A, Battistella M, Feugeas JP, et al. Myelodysplasia cutis vs leukaemia cutis. J Invest Dermatol. 2015;135:2321–2324.
85. Ghoufi L, Ortonne N, Ingen-Housz-Oro S, et al. Histiocytoid Sweet syndrome
is more frequently associated with myelodysplastic syndromes than the classical neutrophilic variant: a comparative series of 62 patients. Medicine. 2016;95:1–10.
86. Bush JW, Wick MR. Cutaneous histiocytoid Sweet syndrome
and its relationship to hematological diseases. J Cutan Pathol. 2016;43:394–399.
87. Baldus CD, Liyanarachchi S, Mrozek K, et al. Acute myeloid leukemia with complex karyotypes and abnormal chromosome 21: amplification discloses overexpression of APP, ETS2, and ERG genes. Proc Natl Acad Sci USA. 2004;101:3915–3920.
88. Goldberg L, Tijssen MR, Birger Y, et al. Genome-scale expression and transcription factor binding profiles reveal therapeutic targets in transgenic ERG myeloid leukemia. Blood. 2013;122:2694–2703.
89. Xu B, Naughton D, Busam K, et al. ERG is a useful immnohistochemical marker to distinguish leukemia cutis from nonneoplastic leukocytic infiltrates in the skin. Am J Dermatopathol. 2016;38:672–677.
90. Gleason BC, Zembowicz A, Granter SR. Non-bullous neutrophilic dermatosis: an uncommon dermatologic manifestation in patients with lupus erythematosus. J Cutan Pathol. 2006;33:721–725.
91. Brinster NK, Nunley J, Pariser R, et al. Nonbullous neutrophilic lupus erythematosus: a newly recognized variant of cutaneous lupus erythematosus. J Am Acad Dermatol. 2012;66:92–97.
92. Ramsey-Goldman R, Franz T, Solano FX, et al. Hydralazine induced lupus and Sweet’s syndrome. Report and review of the literature. J Rheumatol. 1990;17:682–684.
93. Sequeira W, Polisky RB, Alrenga DP. Neutrophilic dermatosis (Sweet’s syndrome). Association with a hydralazine-induced lupus syndrome. Am J Med. 1986;81:558.
94. Servitje O, Ribera M, Juanola X, et al. Acute neutrophilic dermatosis associated with hydralazine-induced lupus. Arch Dermatol. 1987;123:1435.
95. Saeb-Lima M, Charli-Joseph Y, Rodriguez-Acosta ED, et al. Autoimmunity-related neutrophilic dermatosis: a newly described entity that is not exclusive of systemic lupus erythematosus. Am J Dermatopathol. 2013:655–660.
96. Hau E, Vignon Pennamen MD, Battistella M, et al. Neutrophilic skin lesions in autoimmune connective tissue diseases: nine cases and a literature review. Medicine. 2014;93:1–13.
97. Broekaert SM, Böer-Auer A, Kerl K, et al. Neutrophilic epitheliotropism is a histopathologic clue to neutrophilic urticarial dermatosis
. Am J Dermatopathol. 2016;38:39–49.
98. Kieffer C, Cribier B, Lipsker D. Neutrophilic urticarial dermatosis
: a variant of neutrophilic urticaria strongly associated with systemic disease. Report of 9 new cases and review of the literature. Medicine (Baltimore). 2009;88:22–31.
99. Németh T, Mócsai A. The role of neutrophils in autoimmune diseases. Immunol Lett. 2012;143:9–19.
100. Eyles JL, Roberts AW, Metcalf D, et al. Granulocyte colony-stimulating factor and neutrophils—forgotten mediators of inflammatory disease. Nat Clin Pract Rheumatol. 2006;2:500–510.
101. Marzano AV, Fanoni D, Antiga E, et al. Expression of cytokines, chemokines and other effector molecules in two prototypic autoinflammatory skin diseases, pyoderma gangrenosum and Sweet’s syndrome. Clin Exp Immunol. 2014;178:48–56.
102. Caproni M, Torchia D, Cardinali C, et al. Infiltrating cells, related cytokines and chemokine receptors in lesional skin of patients with dermatomyositis. Br J Dermatol. 2004;151:784–791.
103. Essary LR, Wick MR. Cutaneous calciphylaxis
. An underrecognized clinicopathologic entity. Am J Clin Pathol. 2000;113:280–287.
104. Fernandez KH, Liu V, Swick BL. Nonuremic calciphylaxis
associated with histologic changes of pseudoxanthoma elasticum. Am J Dermatopathol. 2013;35:106–108.
105. Jeong HS, Dominguez AR. Calciphylaxis
: controversies in pathogenesis, diagnosis and treatment. Am J Med Sci. 2016;351:217–227.
106. Weenig RH. Pathogenesis of calciphylaxis
: Hans Selye to nuclear factor kappa-B. J Am Acad Dermatol. 2008;58:458–471.
107. Oliveira TM, Frazao JM. Calciphylaxis
: from the disease to the diseased. J Nephrol. 2015;28:531–540.
108. Mochel MC, Arakaki RY, Wang G, et al. Cutaneous calciphylaxis
: a retrospective histopathologic evaluation. Am J Dermatopathol. 2013;35:582–586.
109. Selye H, Grasso S, Dieudonne JM. On the role of adjuvants in calciphylaxis
. Q Rev Allergy Appl Immunol. 1961;15:461–465.
110. Chen TY, Lehman JS, Gibson LE, et al. Histopathology of calciphylaxis
: cohort study with clinical correlations. Am J Dermatopathol. 2017;39:795–802.
111. Halasz CL, Munger DP, Frimmer H, et al. Calciphylaxis
: Comparison of radiologic imaging and histopathology. J Am Acad Dermatol. 2017;77:241–246.e3.
112. Yerram P, Chaudhary K. Calcific uremic arteriolopathy in end stage renal disease: pathophysiology and management. Ochsner J. 2014;14:380–385.
113. Latus J, Kimmel M, Ott G, et al. Early stages of calciphylaxis
: are skin biopsies the answer? Case Rep Dermatol. 2011;3:201–205.
114. Dookhan C, Ortega LM, Nayer A, et al. Perieccrine and pericapillary calcification in calciphylaxis
. J Renal Inj Prev. 2015;4:9–10.
115. Marconi B, Bobyr I, Campanati A, et al. Pseudoxanthoma elasticum and skin: clinical manifestations, histopathology, pathomechanism, perspectives of treatment. Intractable Rare Dis Res. 2015;4:113–122.
116. Cai MM, Smith ER, Brumby C, et al. Fetuin-A-containing calciprotein particle levels can be reduced by dialysis, sodium thiosulphate and plasma exchange. Potential therapeutic implications for calciphylaxis
. Nephrology (Carlton). 2013;18:724–727.
117. Buka R, Wei H, Sapadin A, et al. Pseudoxanthoma elasticum and calcinosis cutis. J Am Acad Dermatol. 2000;43 (2 Pt 1):312–315.
118. Jean L, Bolognia JLJ, Julie V. Schaffer. Dermatology, 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012:47.
119. Jurzyk RS, Ditre CM, Kantor GR, et al. Plaque-type intertriginous cutaneous calcification. Cutis. 1992;49:289–291.
120. Woo TY, Rasmussen JE. Disorders of transepidermal elimination. Part 2. Int J Dermatol. 1985;24:337–348.
121. Saxe N, Beighton P. Cutaneous manifestations of osteoectasia. Clin Exp Dermatol. 1982;7:605–609.
122. Cochran RJ, Wilkin JK. An unusual case of calcinosis cutis. J Am Acad Dermatol. 1983;8:103–106.
123. Nielsen AO, Christensen OB, Hentzer B, et al. Salpeter-induced dermal changes electron-microscopically indistinguishable from pseudoxanthoma elasticum. Acta Derm Venereol. 1978;58:323–327.
124. Mainetti C, Masouye I, Saurat JH. Pseudoxanthoma elasticum-like lesions in the L-tryptophan-induced eosinophilia-myalgia syndrome. J Am Acad Dermatol. 1991;24:657–658.
125. Aessopos A, Savvides P, Stamatelos G, et al. Pseudoxanthoma elasticum-like skin lesions and angioid streaks in beta-thalassemia. Am J Hematol. 1992;41:159–164.
126. Baccarani-Contri M, Bacchelli B, Boraldi F, et al. Characterization of pseudoxanthoma elasticum-like lesions in the skin of patients with beta-thalassemia. J Am Acad Dermatol. 2001;44:33–39.
127. Kasemsarn P, Boonchai W. Pseudoxanthoma elasticum-like lesions in beta-thalassemia/hemoglobin E patient: a case report. J Dermatol. 2013;40:409–410.
128. Yu S, Ming A, Wegman A. Pseudoxanthoma elasticum-like lesions in association with thalassaemia major. Australas J Dermatol. 2009;50:186–189.
129. Nathoo RK, Harb JN, Auerbach J, et al. Pseudoxanthoma elasticum-like changes in nonuremic calciphylaxis
: case series and brief review of a helpful diagnostic clue. J Cutan Pathol. 2017;44:1064–1069.
130. Penn LA, Brinster N. Calciphylaxis
with pseudoxanthoma elasticum-like changes: a case series. J Cutan Pathol. 2018;45:118–121.
131. Lewis KG, Lester BW, Pan TD, et al. Nephrogenic fibrosing dermopathy and calciphylaxis
with pseudoxanthoma elasticum-like changes. J Cutan Pathol. 2006;33:695–700.
132. Nikko AP, Dunningan M, Cockerell CJ. Calciphylaxis
with histologic changes of pseudoxanthoma elasticum. Am J Dermatopathol. 1996;18:396–399.