- Email: [email protected]
Generalized eruptive histiocytosis
Generalized eruptive histiocytosis James L. Seward, MD, Janine C. Malone, MD, and Jeffrey P. Callen, MD Louisville, Kentucky The histiocytic disorders can be broadly categorized into histiocytosis X (Langerhans cell– derived) and non-X types. There are several variants of non-X histiocytoses that tend to occur in a generalized distribution on the body; these include xanthoma disseminatum, generalized eruptive histiocytosis (GEH), progressive nodular histiocytosis, and multicentric reticulohistiocytosis. Clinical and pathologic correlation are required for differentiating among these 4 disorders. We report a case of a middle-aged man in whom small, scattered, symmetrical lesions on the trunk and proximal extremities developed that, after correlating with biopsy specimen and laboratory results, were best classified as a non-X histiocytosis with features of GEH. GEH is a rare generalized non-X histiocytosis that occurs mainly in adults. It is characterized by multiple, scattered, symmetric lesions on the trunk and proximal extremities that are benign in nature and tend to resolve spontaneously. Recent literature has suggested that GEH may be a part of a continuous spectrum of non-X histiocytic disorders. (J Am Acad Dermatol 2004;50:116-20.)
T
he histiocytic disorders can be broadly categorized into histiocytosis X (Langerhans cell– derived) and non-X types. Non-X type histiocytoses are derived from the mononuclearmacrophage system. There are several variants of non-X histiocytoses that tend to occur in a generalized distribution on the body; these include xanthoma disseminatum, generalized eruptive histiocytosis (GEH), progressive nodular histiocytosis, and multicentric reticulohistiocytosis. Clinical and pathologic correlation are required for differentiating among these 4 disorders, and criteria include extent of disease, clinical appearance, distribution, age at onset, laboratory abnormalities (serum lipids), and histologic appearance. We report a case of a middleaged man in whom small, scattered, symmetrical lesions on the trunk and proximal extremities developed that, after correlating with biopsy specimen and laboratory results, were best classified as a non-X histiocytosis with features of GEH.
From the Division of Dermatology, Department of Medicine, University of Louisville School of Medicine. Funding sources: None. Conflicts of interest: None identified. Presented as a poster at the Summer American Academy of Dermatology meeting, New York, New York, July, 2002. Reprint requests: Jeffrey P. Callen, MD, Division of Dermatology, University of Louisville, 310 E Broadway, Louisville, KY 40202. Email: [email protected]. 0190-9622/$30.00 Copyright © 2004 by the American Academy of Dermatology, Inc. doi:10.1016/S0190-9622(03)02789-0
116
CASE REPORT A 55-year-old man developed a progressive eruption of small, scattered, symmetric lesions during a 7-month period on the proximal upper aspect of his extremities and trunk. Initial biopsy specimen of 2 of the lesions by the referring dermatologist showed xanthogranulomas. Treatment of several of the lesions with cryotherapy provided no benefit. Because of concern that the patient could have multicentric reticulohistiocytosis, an extensive laboratory workup including complete blood cell count, comprehensive metabolic profile, antinuclear antibody, anti-Ro antibody, anti-La antibody, erythrocyte sedimentation rate, serum protein electrophoresis, lipid profile, and angiotensin-converting enzyme level did not reveal any abnormalities. In addition, an age-related malignancy screen including a physical examination, colonoscopy, computed tomography scan of chest and abdomen, chest radiograph, and prostate-specific antigen level were then conducted, which were all within normal limits. On presentation to our institution, the patient had hundreds of erythematous to slightly yellowish papules and nodules on the front and back of his trunk and proximal upper aspect of his extremities (Figs 1 and 2). No mucous membrane involvement was evident. Repeated biopsy specimens of 2 of the lesions at our institution were consistent with previous biopsy specimens and showed a dense wedge-shaped infiltrate of spindle-shaped cells admixed with multinucleated giant cells involving the papillary and midreticular dermis (Figs 3 and 4). The infiltrate
J AM ACAD DERMATOL VOLUME 50, NUMBER 1
Seward, Malone, and Callen 117
Fig 3. Wedge-shaped infiltrate of spindle-shaped cells with scattered Langerhans giant cells involved papillary and mid reticular dermis. Oil-Red O, colloidal iron, cytokeratin, and desmin stains were unremarkable. Immunohistochemically, cells expressed CD68 and lysozyme, but were negative for S-100 protein. (Hematoxylin-eosin stain; original magnification ⫻40.)
Fig 1. Hundreds of erythematous to slightly yellowish papules/nodules were observed on patient’s trunk and proximal upper aspect of extremities.
Fig 4. High-power view (⫻100) of Fig 3.
Fig 2. Close-up view of Fig 1.
was positive for CD68 but negative for S-100, confirming a mononuclear-macrophage lineage. Additional staining with Oil-Red O, colloidal iron, cytokeratin, and desmin was unremarkable. After correlating his clinical picture with the pathology, we believed he was best categorized as having a non-X histiocytosis with clinical features of GEH. Because of the reported benign nature of this disorder and its tendency to spontaneously resolve, no treatment other than reassurance was initially given to the patient. During the ensuing months, cryotherapy was performed, which was followed by resolution of several of the lesions.
DISCUSSION Our patient was not readily categorized into one of the generalized non-X histiocytic disorders, al-
though the clinical appearance and course of his eruption are most supportive of GEH. GEH is a rare generalized non-X histiocytosis that was first described by Winklemann and Muller1 in 1963 in 3 healthy adult patients. They described the following features in their group of patients: (1) multiple, widespread, scattered, symmetric lesions on the trunk and proximal extremities, and rarely the mucous membranes; (2) hundreds or even thousands of discrete flesh-colored to bluish-red papular lesions present without grouping; (3) progressive development of new lesions; (4) spontaneous resolution of lesions toward brown macules or complete disappearance; and (5) a benign monomorphous histologic picture composed of an infiltrate of histiocytic cells with stains negative for lipids, mucopolysaccharides, and S-100. Since that time, approximately 20 cases have been described in the literature, including 8 in children (Table I).1-15 Clinically, the presence of erythematous, widely and symmetrically distributed papules without facial or oral involvement or flexural accentuation, and progressive de-
118 Seward, Malone, and Callen
J AM ACAD DERMATOL JANUARY 2004
Table I. Previously reported cases of generalized eruptive histiocytosis Case No.
1
Study
Sex/age at onset
No. of lesions
Location
Duration and/or course
Associated findings
Winkelmann and Muller1 (1963) Winkelmann and Muller1 (1963)
F/51 y
100
Trunk, extremities
No follow-up
None
M/58 y
Thousands
Persisted for at least 8 y
None
F/38 y
Thousands
M/42 y
Numerous
Cleared gradually in 12 y No follow-up
None
4
Winkelmann and Muller1 (1963) Pegum2 (1973)
5
Sohi et al3 (1979)
M/49 y
⬎1000
Trunk, proximal extremities, a few on buccal mucosa Face, trunk, extremities Arms, flanks, buttocks, thighs Generalized
None
6
Winkelmann et al4 (1980) Caputo, Alessi, Allegra5 (1981)
F/3 mo
Numerous
M/27 y
Several hundred
Regressed in a few months, then recurred 2 y later. Persisted until at least 9 y old Resolved spontaneously in 4-5 y
8
Arnold et al6 (1982)
M/52 y
Bobin et al7 (1983)
M/23 y
10
Saijo et al9 (1991)
F/14 y
Dozens
Trunk
11
Caputo et al8 (1987)
M/11 mo
Hundreds
12
Caputo et al8 (1987)
F/11 mo
Hundreds
Trunk, neck, head, extremities Face, trunk
Persisted for at least 20 y Partial regression over 2 y Partial regression; some new lesions occurred Disappeared in 5 y
None
9
Not described 60 Trunk, extremities
13
Caputo et al8 (1987)
M/10 mo
⬍50
Trunk, scrotum
14
Caputo et al8 (1987)
F/44 mo
50-100
Trunk, axillae, face
15
Stables and MacKie10 (1992)
F/55 y
Hundreds
16
Goerdt et al11 (1994)
M/69 y
Hundreds
17
Repiso et al12 (1995)
M/4 y
⬎100
18
Jang et al13 (1999)
M/3 mo
Multiple
19
Wee et al14 (2000)
M/9 y
Multiple
20
Marzano, Facchetti, Caputo15 (2002)
F/33 y
30
Arms, trunk, upper thighs, a few on face Trunk, extensor thighs Face, trunk, proximal extremities Face, trunk, groin, upper and lower limbs Trunk, proximal extremities Trunk, extremities
2
3
7
Extensor limbs, buttocks Lower thorax, abdomen, inguinal fold, proximal extremities Disseminated
Mostly regressed in 6y Mostly regressed in 2y Mostly regressed in 3y Present for at least 24 mo
Cholesterol 247
Glaucoma and uveitis None
None None None None None None None
Persisted for at least 5 y Evolved into xanthoma disseminatum No follow-up
Cholesterol 260
Started to resolve at age 9 y Resolved over 6 mo
None
Later developed diabetes insipidus None
None
F, Female; M, male.
velopment of new lesions with spontaneous resolution over time seen in our patient is characteristic of GEH. However, the presence of histiocytes with
scattered multinucleate forms in our patient is outside of the typical histologic picture for that disorder. Although the presence of numerous multinucleate
Seward, Malone, and Callen 119
J AM ACAD DERMATOL VOLUME 50, NUMBER 1
Table II. Differential diagnosis of generalized non-X histioctyoses Generalized eruptive histiocytosis
Age/Sex Pattern and distribution Mucous membrane involvement Associated abnormalities
Adults ⬎ children Generalized No None
Xanthoma disseminatum
Progressive nodular histiocytosis
Young men Prominent in flexural folds Yes
Children ⬎ adults Prominent facial involvement Yes
Older women ⬎ men Prominent acrally
Diabetes insipidus
None
Arthropathy “arthritis mutilans,” increased risk of malignancy
giant cells is an unusual histopathologic finding for GEH, the presence of giant cells should not mitigate completely against that diagnosis. The clinical criteria for the diagnosis set forth by Winklemann and Muller1 has been fulfilled. The only histologic criterion mentioned by these authors was the presence of “a benign histologic picture of mononuclear histiocytic cells.”1 Coldiron et al,16 in their article describing a generalized papular eruption in a 32-yearold man, found multinucleate histiocytes in the seventh of 9 biopsy specimens taken during a 1-year period. All other biopsy specimens were replete of giant cells, exhibiting only a monomorphic infiltrate of mononuclear histiocytes with variable numbers of inflammatory cells. The differential diagnosis in our patient should also include xanthoma disseminatum, progressive nodular histiocytosis, multicentric reticulohistiocytosis, and papular sarcoid (Table II). Xanthoma disseminatum is a rare disorder that tends to occur in young men with prominent flexural and mucocutaneous lesions. Histopathogically, one sees “foamy” histiocytes that were not seen in our patient. Diabetes insipidus secondary to xanthomatous involvement of the pituitary gland has been shown to occur in approximately 40% to 50% of cases of xanthoma disseminatum.17 The histopathologic pattern seen in our patient has also been described in progressive nodular histiocytosis; however, this condition tends to occur in children with prominent facial involvement, grouping of lesions, and associated mucosal involvement.18 Lastly, multicentric reticulohistiocytosis often occurs in older women with an acral predilection and associated arthropathy. Clinically, and somewhat less convincingly histologically, papular sarcoid would also be considered in the differential diagnosis. In most cases, however, the papular variant of sarcoidosis would manifest with a histologic pattern similar to other types of cutaneous sarcoidosis characterized by collections of epithelioid tubercles of some definition rather than a diffuse interstitial histiocytic dermal infiltrate. Again,
Multicentric reticulohistiocytosis
No
clinical evaluation for the presence of systemic sarcoidosis has not borne out any signs of this disorder. Several authors11,16,19 have noted that classifying the non-X histiocytoses into specific entities is often difficult because there are few clinical, histologic, or ultrastructural criteria that are absolute. In addition, Goerdt et al11 noted that the non-X histiocytoses may represent a spectrum of disease rather than discrete entities. Many authors12,20 believe that GEH is an early undifferentiated stage of various histiocytic disorders; in fact, a case of GEH evolving into xanthoma disseminatum was reported in a 4-yearold boy.12 Jang et al13 agreed, proposing that GEH be divided into 2 subsets: an indifferent stage of other histiocytic disorders and a specific condition without subsequent disorder. Therefore, close clinical follow up of patients is recommended. If the clinical lesions change or systemic manifestations occur a repeated biopsy specimen of a newer lesion and systemic review are necessary to rule out a more serious condition.14 In conclusion, we recognize the rarity of the disorder and lack of diagnostic histopathologic findings in our case. With the clinical presentation of our patient, the course of our patient’s disease, and the pertinent negative findings regarding systemic involvement, we believe our patient has features most compatible with GEH. Close clinical follow-up is planned, however, to evaluate for possible evolution of his cutaneous disease. We thank Kathryn V. Balazs, DO, who initially referred to us and provided follow-up care for this case. REFERENCES 1. Winkelmann RK, Muller SA. Generalized eruptive histiocytoma: a benign papular histiocytic reticulosis. Arch Dermatol 1963;88: 586-96. 2. Pegum JS. Generalized eruptive histiocytoma. Proc R Soc Med 1973;56:1175-6. 3. Sohi AS, Tiwari VD, Subramanian CSV, Chakraborty M. Generalized eruptive histiocytoma: a case report with a review of the literature. Dermatologica 1979;159:471-5.
120 Seward, Malone, and Callen
4. Winklemann RK, Kossard S, Fraga S. Eruptive histiocytoma of childhood. Arch Dermatol 1980;116:565-70. 5. Caputo R, Alessi E, Allegra F, et al. Generalized eruptive histiocytoma: a clinical, histological and ultrastructural study. Arch Dermatol 1981;117:216-21. 6. Arnold ML, Wirth H, Anton-Lamprect I, Petzoldt D. Generalisierte eruptive histiozytome. Hautarzt 1982;33:428-37. 7. Bobin P, Carsuzaa F, Seurat P, Luca D. Histiocytome eruptive generalize. Ann Dermatol Venereol 1983;110:817-24. 8. Caputo R, Ermacora E, Gelmetti C, Berti E, Gianni E, Nigro A. Generalized eruptive histiocytoma in children. J Am Acad Dermatol 1987;17:449-54. 9. Siajo S, Hara M, Kuramoto Y, Tagami H. Generalized eruptive histiocytoma: a report of a variant case showing the presence of dermal indeterminate cells. J Cutan Pathol 1991;18:134-6. 10. Stables GI, Mackie RM. Generalized eruptive histiocytoma. Br J Dermatol 1992;126:196-9. 11. Goerdt S, Bonsmann G, Sunderkotter C, Grabbe S, Luger T, Kolde G. A unique non-Langerhans cell histiocytosis with some features of generalized eruptive histiocytoma. J Am Acad Dermatol 1994;31:322-6. 12. Repiso T, Roca-Miralles M, Kanitakis J, Castells-Rodellas A. Generalized eruptive histiocytoma evolving into xanthoma disseminatum in a 4-year-old boy. Br J Dermatol 1995;132:978-82.
J AM ACAD DERMATOL JANUARY 2004
13. Jang KA, Lee HJ, Choi JH, Sang KJ, Koh JK, Moon KC. Generalized eruptive histiocytoma of childhood. Br J Dermatol 1999;140:174-6. 14. Wee SH, Kim HS, Chang SN, Kim DK, Park WH. Generalized eruptive histiocytoma: a pediatric case. Pediatr Dermatol 2000;17: 453-5. 15. Marzano AV, Facchetti M, Caputo R. Guess what! Generalized eruptive histiocytosis (histiocytoma). Eur J Dermatol 2002;12: 205-6. 16. Coldiron BM, Cruz PD, Freeman RG, Sontheimer RD. Benign non-X histiocytosis: a unique case bridging several of the non-X histiocytic syndromes. J Am Acad Dermatol 1988;18: 1282-9. 17. Beurey J, Lamaze B, Weber M, Delrous JL, Kremer B, Chaulieu Y. Xanthoma disseminatum (syndrome de Montgomery). Ann Dermatol Venereol 1979;106:353-9. 18. Ruiz AG, Ruiz AI, Fraile HA, Martinez IP, Munoz MG. Progressive nodular histiocytosis accompanied by systemic disorders. Br J Dermatol 2000;143:628-31. 19. Giannoti F, Caputo R. Histiocytic syndromes: a review. J Am Acad Dermatol 1985;13:383-404. 20. Winkelmann RK. Cutaneous syndromes of non-X histiocytoses. Arch Dermatol 1981;117:667-72. 21. Rapini R. Multicentric reticulohistiocytosis. Clin Dermatol 1993; 11:107.
T
he histiocytic disorders can be broadly categorized into histiocytosis X (Langerhans cell– derived) and non-X types. Non-X type histiocytoses are derived from the mononuclearmacrophage system. There are several variants of non-X histiocytoses that tend to occur in a generalized distribution on the body; these include xanthoma disseminatum, generalized eruptive histiocytosis (GEH), progressive nodular histiocytosis, and multicentric reticulohistiocytosis. Clinical and pathologic correlation are required for differentiating among these 4 disorders, and criteria include extent of disease, clinical appearance, distribution, age at onset, laboratory abnormalities (serum lipids), and histologic appearance. We report a case of a middleaged man in whom small, scattered, symmetrical lesions on the trunk and proximal extremities developed that, after correlating with biopsy specimen and laboratory results, were best classified as a non-X histiocytosis with features of GEH.
From the Division of Dermatology, Department of Medicine, University of Louisville School of Medicine. Funding sources: None. Conflicts of interest: None identified. Presented as a poster at the Summer American Academy of Dermatology meeting, New York, New York, July, 2002. Reprint requests: Jeffrey P. Callen, MD, Division of Dermatology, University of Louisville, 310 E Broadway, Louisville, KY 40202. Email: [email protected]. 0190-9622/$30.00 Copyright © 2004 by the American Academy of Dermatology, Inc. doi:10.1016/S0190-9622(03)02789-0
116
CASE REPORT A 55-year-old man developed a progressive eruption of small, scattered, symmetric lesions during a 7-month period on the proximal upper aspect of his extremities and trunk. Initial biopsy specimen of 2 of the lesions by the referring dermatologist showed xanthogranulomas. Treatment of several of the lesions with cryotherapy provided no benefit. Because of concern that the patient could have multicentric reticulohistiocytosis, an extensive laboratory workup including complete blood cell count, comprehensive metabolic profile, antinuclear antibody, anti-Ro antibody, anti-La antibody, erythrocyte sedimentation rate, serum protein electrophoresis, lipid profile, and angiotensin-converting enzyme level did not reveal any abnormalities. In addition, an age-related malignancy screen including a physical examination, colonoscopy, computed tomography scan of chest and abdomen, chest radiograph, and prostate-specific antigen level were then conducted, which were all within normal limits. On presentation to our institution, the patient had hundreds of erythematous to slightly yellowish papules and nodules on the front and back of his trunk and proximal upper aspect of his extremities (Figs 1 and 2). No mucous membrane involvement was evident. Repeated biopsy specimens of 2 of the lesions at our institution were consistent with previous biopsy specimens and showed a dense wedge-shaped infiltrate of spindle-shaped cells admixed with multinucleated giant cells involving the papillary and midreticular dermis (Figs 3 and 4). The infiltrate
J AM ACAD DERMATOL VOLUME 50, NUMBER 1
Seward, Malone, and Callen 117
Fig 3. Wedge-shaped infiltrate of spindle-shaped cells with scattered Langerhans giant cells involved papillary and mid reticular dermis. Oil-Red O, colloidal iron, cytokeratin, and desmin stains were unremarkable. Immunohistochemically, cells expressed CD68 and lysozyme, but were negative for S-100 protein. (Hematoxylin-eosin stain; original magnification ⫻40.)
Fig 1. Hundreds of erythematous to slightly yellowish papules/nodules were observed on patient’s trunk and proximal upper aspect of extremities.
Fig 4. High-power view (⫻100) of Fig 3.
Fig 2. Close-up view of Fig 1.
was positive for CD68 but negative for S-100, confirming a mononuclear-macrophage lineage. Additional staining with Oil-Red O, colloidal iron, cytokeratin, and desmin was unremarkable. After correlating his clinical picture with the pathology, we believed he was best categorized as having a non-X histiocytosis with clinical features of GEH. Because of the reported benign nature of this disorder and its tendency to spontaneously resolve, no treatment other than reassurance was initially given to the patient. During the ensuing months, cryotherapy was performed, which was followed by resolution of several of the lesions.
DISCUSSION Our patient was not readily categorized into one of the generalized non-X histiocytic disorders, al-
though the clinical appearance and course of his eruption are most supportive of GEH. GEH is a rare generalized non-X histiocytosis that was first described by Winklemann and Muller1 in 1963 in 3 healthy adult patients. They described the following features in their group of patients: (1) multiple, widespread, scattered, symmetric lesions on the trunk and proximal extremities, and rarely the mucous membranes; (2) hundreds or even thousands of discrete flesh-colored to bluish-red papular lesions present without grouping; (3) progressive development of new lesions; (4) spontaneous resolution of lesions toward brown macules or complete disappearance; and (5) a benign monomorphous histologic picture composed of an infiltrate of histiocytic cells with stains negative for lipids, mucopolysaccharides, and S-100. Since that time, approximately 20 cases have been described in the literature, including 8 in children (Table I).1-15 Clinically, the presence of erythematous, widely and symmetrically distributed papules without facial or oral involvement or flexural accentuation, and progressive de-
118 Seward, Malone, and Callen
J AM ACAD DERMATOL JANUARY 2004
Table I. Previously reported cases of generalized eruptive histiocytosis Case No.
1
Study
Sex/age at onset
No. of lesions
Location
Duration and/or course
Associated findings
Winkelmann and Muller1 (1963) Winkelmann and Muller1 (1963)
F/51 y
100
Trunk, extremities
No follow-up
None
M/58 y
Thousands
Persisted for at least 8 y
None
F/38 y
Thousands
M/42 y
Numerous
Cleared gradually in 12 y No follow-up
None
4
Winkelmann and Muller1 (1963) Pegum2 (1973)
5
Sohi et al3 (1979)
M/49 y
⬎1000
Trunk, proximal extremities, a few on buccal mucosa Face, trunk, extremities Arms, flanks, buttocks, thighs Generalized
None
6
Winkelmann et al4 (1980) Caputo, Alessi, Allegra5 (1981)
F/3 mo
Numerous
M/27 y
Several hundred
Regressed in a few months, then recurred 2 y later. Persisted until at least 9 y old Resolved spontaneously in 4-5 y
8
Arnold et al6 (1982)
M/52 y
Bobin et al7 (1983)
M/23 y
10
Saijo et al9 (1991)
F/14 y
Dozens
Trunk
11
Caputo et al8 (1987)
M/11 mo
Hundreds
12
Caputo et al8 (1987)
F/11 mo
Hundreds
Trunk, neck, head, extremities Face, trunk
Persisted for at least 20 y Partial regression over 2 y Partial regression; some new lesions occurred Disappeared in 5 y
None
9
Not described 60 Trunk, extremities
13
Caputo et al8 (1987)
M/10 mo
⬍50
Trunk, scrotum
14
Caputo et al8 (1987)
F/44 mo
50-100
Trunk, axillae, face
15
Stables and MacKie10 (1992)
F/55 y
Hundreds
16
Goerdt et al11 (1994)
M/69 y
Hundreds
17
Repiso et al12 (1995)
M/4 y
⬎100
18
Jang et al13 (1999)
M/3 mo
Multiple
19
Wee et al14 (2000)
M/9 y
Multiple
20
Marzano, Facchetti, Caputo15 (2002)
F/33 y
30
Arms, trunk, upper thighs, a few on face Trunk, extensor thighs Face, trunk, proximal extremities Face, trunk, groin, upper and lower limbs Trunk, proximal extremities Trunk, extremities
2
3
7
Extensor limbs, buttocks Lower thorax, abdomen, inguinal fold, proximal extremities Disseminated
Mostly regressed in 6y Mostly regressed in 2y Mostly regressed in 3y Present for at least 24 mo
Cholesterol 247
Glaucoma and uveitis None
None None None None None None None
Persisted for at least 5 y Evolved into xanthoma disseminatum No follow-up
Cholesterol 260
Started to resolve at age 9 y Resolved over 6 mo
None
Later developed diabetes insipidus None
None
F, Female; M, male.
velopment of new lesions with spontaneous resolution over time seen in our patient is characteristic of GEH. However, the presence of histiocytes with
scattered multinucleate forms in our patient is outside of the typical histologic picture for that disorder. Although the presence of numerous multinucleate
Seward, Malone, and Callen 119
J AM ACAD DERMATOL VOLUME 50, NUMBER 1
Table II. Differential diagnosis of generalized non-X histioctyoses Generalized eruptive histiocytosis
Age/Sex Pattern and distribution Mucous membrane involvement Associated abnormalities
Adults ⬎ children Generalized No None
Xanthoma disseminatum
Progressive nodular histiocytosis
Young men Prominent in flexural folds Yes
Children ⬎ adults Prominent facial involvement Yes
Older women ⬎ men Prominent acrally
Diabetes insipidus
None
Arthropathy “arthritis mutilans,” increased risk of malignancy
giant cells is an unusual histopathologic finding for GEH, the presence of giant cells should not mitigate completely against that diagnosis. The clinical criteria for the diagnosis set forth by Winklemann and Muller1 has been fulfilled. The only histologic criterion mentioned by these authors was the presence of “a benign histologic picture of mononuclear histiocytic cells.”1 Coldiron et al,16 in their article describing a generalized papular eruption in a 32-yearold man, found multinucleate histiocytes in the seventh of 9 biopsy specimens taken during a 1-year period. All other biopsy specimens were replete of giant cells, exhibiting only a monomorphic infiltrate of mononuclear histiocytes with variable numbers of inflammatory cells. The differential diagnosis in our patient should also include xanthoma disseminatum, progressive nodular histiocytosis, multicentric reticulohistiocytosis, and papular sarcoid (Table II). Xanthoma disseminatum is a rare disorder that tends to occur in young men with prominent flexural and mucocutaneous lesions. Histopathogically, one sees “foamy” histiocytes that were not seen in our patient. Diabetes insipidus secondary to xanthomatous involvement of the pituitary gland has been shown to occur in approximately 40% to 50% of cases of xanthoma disseminatum.17 The histopathologic pattern seen in our patient has also been described in progressive nodular histiocytosis; however, this condition tends to occur in children with prominent facial involvement, grouping of lesions, and associated mucosal involvement.18 Lastly, multicentric reticulohistiocytosis often occurs in older women with an acral predilection and associated arthropathy. Clinically, and somewhat less convincingly histologically, papular sarcoid would also be considered in the differential diagnosis. In most cases, however, the papular variant of sarcoidosis would manifest with a histologic pattern similar to other types of cutaneous sarcoidosis characterized by collections of epithelioid tubercles of some definition rather than a diffuse interstitial histiocytic dermal infiltrate. Again,
Multicentric reticulohistiocytosis
No
clinical evaluation for the presence of systemic sarcoidosis has not borne out any signs of this disorder. Several authors11,16,19 have noted that classifying the non-X histiocytoses into specific entities is often difficult because there are few clinical, histologic, or ultrastructural criteria that are absolute. In addition, Goerdt et al11 noted that the non-X histiocytoses may represent a spectrum of disease rather than discrete entities. Many authors12,20 believe that GEH is an early undifferentiated stage of various histiocytic disorders; in fact, a case of GEH evolving into xanthoma disseminatum was reported in a 4-yearold boy.12 Jang et al13 agreed, proposing that GEH be divided into 2 subsets: an indifferent stage of other histiocytic disorders and a specific condition without subsequent disorder. Therefore, close clinical follow up of patients is recommended. If the clinical lesions change or systemic manifestations occur a repeated biopsy specimen of a newer lesion and systemic review are necessary to rule out a more serious condition.14 In conclusion, we recognize the rarity of the disorder and lack of diagnostic histopathologic findings in our case. With the clinical presentation of our patient, the course of our patient’s disease, and the pertinent negative findings regarding systemic involvement, we believe our patient has features most compatible with GEH. Close clinical follow-up is planned, however, to evaluate for possible evolution of his cutaneous disease. We thank Kathryn V. Balazs, DO, who initially referred to us and provided follow-up care for this case. REFERENCES 1. Winkelmann RK, Muller SA. Generalized eruptive histiocytoma: a benign papular histiocytic reticulosis. Arch Dermatol 1963;88: 586-96. 2. Pegum JS. Generalized eruptive histiocytoma. Proc R Soc Med 1973;56:1175-6. 3. Sohi AS, Tiwari VD, Subramanian CSV, Chakraborty M. Generalized eruptive histiocytoma: a case report with a review of the literature. Dermatologica 1979;159:471-5.
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