Clinical Review & Education
JAMA Dermatology Clinicopathological Challenge
Multiple Firm Nodules and Tender, Indurated Plaques Jeannette Olazagasti, BS; Audrey S. Wang, MD; Rivkah Isseroff, MD
A man in his 30s with a history of multiple medical conditions, including hypertension, congestive heart failure (receiving chronic diuretic therapy), chronic renal insufficiency, and pulmonary embolus (receiving warfarin therapy), presented with multiple firm nodules that extruded a thin, white, milky fluid within tender, hyperpigmented, indurated plaques on the lower abdomen (Figure, A). He also had numerous smaller nondraining, yellow-white nodules on an erythematous to hyperpigmented base on the bilateral medial thighs (Figure, B). A few scattered firm, yellow-white subcutaneous nod-
A
ules were also seen on the extensor upper extremities. The lesions appeared approximately 1 year prior to our evaluation of his lower abdomen, where he had injected enoxaparin sodium subcutaneously for 4 days. Six months later, similar lesions appeared on his medial thighs and upper extremities without prior trauma or injection. The patient reported no fevers, chills, joint pain, or swelling. He admitted to social alcohol use. A punch biopsy was obtained of a nondraining yellow-white nodule on the left upper arm (Figure, C). What is your diagnosis?
C
B
Figure. A, Lower abdomen with multiple firm nodules that extruded a thin, white, milky fluid within tender, hyperpigmented, indurated plaques. B, Right medial thigh with numerous small, nondraining, yellow-white nodules and plaques on an erythematous to hyperpigmented base. C, Formalin-fixed biopsy
jamadermatology.com
specimen from the left upper arm showing deposits of amorphous, amphophilic, fine fibrillary acellular material surrounded by a sparse lymphohistiocytic infiltrate in the reticular dermis (hematoxylin-eosin, original magnification ×10).
JAMA Dermatology May 2014 Volume 150, Number 5
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/22/2015
569
Clinical Review & Education JAMA Dermatology Clinicopathological Challenge
Diagnosis Cutaneous miliarial gout
Microscopic Findings and Clinical Course The formalin-fixed biopsy specimen from the left upper arm showed changes consistent with tophaceous gout in the dermis (Figure, C). Specifically, deposits of amorphous, amphophilic, fine fibrillary acellular material surrounded by a sparse lymphohistiocytic infiltrate were identified in the reticular dermis. Findings from polarized microscopy of the specimen were negative for refractile elements. The subcutis was not adequately represented in the specimen, impairing our ability to assess for deeper involvement. Several weeks prior to our evaluation, an outside health care professional had prescribed allopurinol, 300 mg by mouth twice daily, and a prednisone taper, but the patient reported no improvement in the lesions or his symptoms. Laboratory evaluation under our care was notable for a serum creatinine level of 1.4 to 1.9 mg/dL (to convert to micromoles per liter, multiply by 88.4) and a serum uric acid level of 5.4 mg/dL (reference range, 3.9-8.0 mg/dL) (to convert to micromoles per liter, multiply by 59.485). After being discharged from the hospital, he was unable to present to our clinic for further care.
Discussion Cutaneous deposition diseases involve accumulation of endogenous or exogenous materials, usually in the dermis but also in the subcutis. Cutaneous lesions of gout, known as tophi, are composed of dermal aggregates of monosodium urate (MSU) crystals often surrounded by macrophages and foreign body giant cells. When fixed in alcohol rather than formalin, the needle-shaped crystals are preserved and doubly refractile under polarized light.1 Tophi typically appear within or around joints and on the ear helices several years after the onset of gouty arthritis.2 However, tophi may be the first manifestation of gout.3-6 In a review of 29 such cases, 18 involved the fingers, while only 1 involved the legs.4 ARTICLE INFORMATION
REFERENCES
Author Affiliations: School of Medicine, University of Puerto Rico, San Juan, Puerto Rico (Olazagasti); University of California, Davis, Sacramento (Wang, Isseroff).
1. Molina-Ruiz AM, Cerroni L, Kutzner H, Requena L. Cutaneous deposits [published online January 2, 2013]. Am J Dermatopathol. doi:10.1097 /DAD.0b013e3182740122.
Corresponding Author: Audrey S. Wang, MD, Department of Dermatology, University of California, Davis, 3301 C St, Ste 1400, Sacramento, CA 95816 ([email protected]).
2. Forbess LJ, Fields TR. The broad spectrum of urate crystal deposition: unusual presentations of gouty tophi. Semin Arthritis Rheum. 2012;42(2):146-154.
Section Editor: Molly A. Hinshaw, MD; Assistant Section Editors: Soon Bahrami, MD; Nicole Fett, MD, MSCE; Anna K. Haemel, MD; Arni K. Kristjansson, MD; Lori D. Prok, MD.
3. Gupta A, Rai S, Sinha R, Achar C. Tophi as an initial manifestation of gout. J Cytol. 2009;26(4):165-166.
Published Online: March 26, 2014. doi:10.1001/jamadermatol.2013.8734. Conflict of Interest Disclosures: None reported. Additional Contributions: Maxwell Fung, MD, Departments of Dermatology and Pathology, University of California, Davis, assisted with interpretation of the histopathologic features associated with this case. No compensation was received for his assistance on this report.
570
Miliarial gout and gouty panniculitis are 2 rare cutaneous manifestations of gout that may precede or follow the onset of arthritic symptoms. The term miliarial gout was first coined by Shukla et al7 in 2007 to describe a patient with hyperuricemia and multiple tiny milia-like papules containing white or cream-colored material on an erythematous base. The lesions were located on the forearms, shins, and inner thighs, and skin biopsy specimens fixed in alcohol demonstrated doubly refractile MSU crystals.7 Gouty panniculitis, first described in 1977,8 is characterized by indurated, erythematous subcutaneous nodules or plaques, with or without pain, located predominantly on the lower extremities.9 The lesions may ulcerate and drain a serous or opaque fluid, which contains the MSU crystals. Histologically, MSU crystals deposited in the subcutis are associated with a lobular panniculitis and foreign body granulomas but no vasculitis.9 The pathogenesis of this condition is poorly understood but is thought to be related to inflammatory changes secondary to MSU crystal–induced disruption of arterial flow and microtrauma of the capillary walls and adipose tissue.9 Though most cases exhibit hyperuricemia, some patients with normal uric acid levels may also develop these lesions,10 as did our patient. Allopurinol has been used to treat both miliarial gout and gouty panniculitis, though an extended course of 2 to 3 years may be required to achieve clearance of the lesions.9 A short course of lowdose corticosteroids may be considered for an anti-inflammatory effect and to help alleviate pain associated with panniculitis.9 Our case had clinical features of both miliarial and panniculitic gout in the absence of arthritis and hyperuricemia. Although our biopsy was not deep enough to assess for involvement of the subcutis, the tender, indurated, draining plaques on the abdomen and medial thighs clinically resembled those of gouty panniculitis. The patient also had several risk factors for developing intradermal gout, including hypertension, renal insufficiency, and chronic diuretic therapy.7 This case highlights the importance of considering atypical cutaneous gout in the differential diagnosis of deposition disorders.
4. Iglesias A, Londono JC, Saaibi DL, Peña M, Lizarazo H, Gonzalez EB. Gout nodulosis: widespread subcutaneous deposits without gout. Arthritis Care Res. 1996;9(1):74-77.
6. Wernick R, Winkler C, Campbell S. Tophi as the initial manifestation of gout: report of six cases and review of the literature. Arch Intern Med. 1992;152(4):873-876. 7. Shukla R, Vender RB, Alhabeeb A, Salama S, Murphy F. Miliarial gout (a new entity). J Cutan Med Surg. 2007;11(1):31-34. 8. Niemi KM. Panniculitis of the legs with urate crystal deposition. Arch Dermatol. 1977;113(5):655-656. 9. Ochoa CD, Valderrama V, Mejia J, et al. Panniculitis: another clinical expression of gout. Rheumatol Int. 2011;31(6):831-835. 10. Dahiya A, Leach J, Levy H. Gouty panniculitis in a healthy male. J Am Acad Dermatol. 2007;57(2)(Suppl):S52-S54.
5. Koley S, Salodkar A, Choudhary S, Bhake A, Singhania K, Choudhury M. Tophi as first manifestation of gout. Indian J Dermatol Venereol Leprol. 2010;76(4):393-396.
JAMA Dermatology May 2014 Volume 150, Number 5
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/22/2015
jamadermatology.com
JAMA Dermatology Clinicopathological Challenge
Multiple Firm Nodules and Tender, Indurated Plaques Jeannette Olazagasti, BS; Audrey S. Wang, MD; Rivkah Isseroff, MD
A man in his 30s with a history of multiple medical conditions, including hypertension, congestive heart failure (receiving chronic diuretic therapy), chronic renal insufficiency, and pulmonary embolus (receiving warfarin therapy), presented with multiple firm nodules that extruded a thin, white, milky fluid within tender, hyperpigmented, indurated plaques on the lower abdomen (Figure, A). He also had numerous smaller nondraining, yellow-white nodules on an erythematous to hyperpigmented base on the bilateral medial thighs (Figure, B). A few scattered firm, yellow-white subcutaneous nod-
A
ules were also seen on the extensor upper extremities. The lesions appeared approximately 1 year prior to our evaluation of his lower abdomen, where he had injected enoxaparin sodium subcutaneously for 4 days. Six months later, similar lesions appeared on his medial thighs and upper extremities without prior trauma or injection. The patient reported no fevers, chills, joint pain, or swelling. He admitted to social alcohol use. A punch biopsy was obtained of a nondraining yellow-white nodule on the left upper arm (Figure, C). What is your diagnosis?
C
B
Figure. A, Lower abdomen with multiple firm nodules that extruded a thin, white, milky fluid within tender, hyperpigmented, indurated plaques. B, Right medial thigh with numerous small, nondraining, yellow-white nodules and plaques on an erythematous to hyperpigmented base. C, Formalin-fixed biopsy
jamadermatology.com
specimen from the left upper arm showing deposits of amorphous, amphophilic, fine fibrillary acellular material surrounded by a sparse lymphohistiocytic infiltrate in the reticular dermis (hematoxylin-eosin, original magnification ×10).
JAMA Dermatology May 2014 Volume 150, Number 5
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/22/2015
569
Clinical Review & Education JAMA Dermatology Clinicopathological Challenge
Diagnosis Cutaneous miliarial gout
Microscopic Findings and Clinical Course The formalin-fixed biopsy specimen from the left upper arm showed changes consistent with tophaceous gout in the dermis (Figure, C). Specifically, deposits of amorphous, amphophilic, fine fibrillary acellular material surrounded by a sparse lymphohistiocytic infiltrate were identified in the reticular dermis. Findings from polarized microscopy of the specimen were negative for refractile elements. The subcutis was not adequately represented in the specimen, impairing our ability to assess for deeper involvement. Several weeks prior to our evaluation, an outside health care professional had prescribed allopurinol, 300 mg by mouth twice daily, and a prednisone taper, but the patient reported no improvement in the lesions or his symptoms. Laboratory evaluation under our care was notable for a serum creatinine level of 1.4 to 1.9 mg/dL (to convert to micromoles per liter, multiply by 88.4) and a serum uric acid level of 5.4 mg/dL (reference range, 3.9-8.0 mg/dL) (to convert to micromoles per liter, multiply by 59.485). After being discharged from the hospital, he was unable to present to our clinic for further care.
Discussion Cutaneous deposition diseases involve accumulation of endogenous or exogenous materials, usually in the dermis but also in the subcutis. Cutaneous lesions of gout, known as tophi, are composed of dermal aggregates of monosodium urate (MSU) crystals often surrounded by macrophages and foreign body giant cells. When fixed in alcohol rather than formalin, the needle-shaped crystals are preserved and doubly refractile under polarized light.1 Tophi typically appear within or around joints and on the ear helices several years after the onset of gouty arthritis.2 However, tophi may be the first manifestation of gout.3-6 In a review of 29 such cases, 18 involved the fingers, while only 1 involved the legs.4 ARTICLE INFORMATION
REFERENCES
Author Affiliations: School of Medicine, University of Puerto Rico, San Juan, Puerto Rico (Olazagasti); University of California, Davis, Sacramento (Wang, Isseroff).
1. Molina-Ruiz AM, Cerroni L, Kutzner H, Requena L. Cutaneous deposits [published online January 2, 2013]. Am J Dermatopathol. doi:10.1097 /DAD.0b013e3182740122.
Corresponding Author: Audrey S. Wang, MD, Department of Dermatology, University of California, Davis, 3301 C St, Ste 1400, Sacramento, CA 95816 ([email protected]).
2. Forbess LJ, Fields TR. The broad spectrum of urate crystal deposition: unusual presentations of gouty tophi. Semin Arthritis Rheum. 2012;42(2):146-154.
Section Editor: Molly A. Hinshaw, MD; Assistant Section Editors: Soon Bahrami, MD; Nicole Fett, MD, MSCE; Anna K. Haemel, MD; Arni K. Kristjansson, MD; Lori D. Prok, MD.
3. Gupta A, Rai S, Sinha R, Achar C. Tophi as an initial manifestation of gout. J Cytol. 2009;26(4):165-166.
Published Online: March 26, 2014. doi:10.1001/jamadermatol.2013.8734. Conflict of Interest Disclosures: None reported. Additional Contributions: Maxwell Fung, MD, Departments of Dermatology and Pathology, University of California, Davis, assisted with interpretation of the histopathologic features associated with this case. No compensation was received for his assistance on this report.
570
Miliarial gout and gouty panniculitis are 2 rare cutaneous manifestations of gout that may precede or follow the onset of arthritic symptoms. The term miliarial gout was first coined by Shukla et al7 in 2007 to describe a patient with hyperuricemia and multiple tiny milia-like papules containing white or cream-colored material on an erythematous base. The lesions were located on the forearms, shins, and inner thighs, and skin biopsy specimens fixed in alcohol demonstrated doubly refractile MSU crystals.7 Gouty panniculitis, first described in 1977,8 is characterized by indurated, erythematous subcutaneous nodules or plaques, with or without pain, located predominantly on the lower extremities.9 The lesions may ulcerate and drain a serous or opaque fluid, which contains the MSU crystals. Histologically, MSU crystals deposited in the subcutis are associated with a lobular panniculitis and foreign body granulomas but no vasculitis.9 The pathogenesis of this condition is poorly understood but is thought to be related to inflammatory changes secondary to MSU crystal–induced disruption of arterial flow and microtrauma of the capillary walls and adipose tissue.9 Though most cases exhibit hyperuricemia, some patients with normal uric acid levels may also develop these lesions,10 as did our patient. Allopurinol has been used to treat both miliarial gout and gouty panniculitis, though an extended course of 2 to 3 years may be required to achieve clearance of the lesions.9 A short course of lowdose corticosteroids may be considered for an anti-inflammatory effect and to help alleviate pain associated with panniculitis.9 Our case had clinical features of both miliarial and panniculitic gout in the absence of arthritis and hyperuricemia. Although our biopsy was not deep enough to assess for involvement of the subcutis, the tender, indurated, draining plaques on the abdomen and medial thighs clinically resembled those of gouty panniculitis. The patient also had several risk factors for developing intradermal gout, including hypertension, renal insufficiency, and chronic diuretic therapy.7 This case highlights the importance of considering atypical cutaneous gout in the differential diagnosis of deposition disorders.
4. Iglesias A, Londono JC, Saaibi DL, Peña M, Lizarazo H, Gonzalez EB. Gout nodulosis: widespread subcutaneous deposits without gout. Arthritis Care Res. 1996;9(1):74-77.
6. Wernick R, Winkler C, Campbell S. Tophi as the initial manifestation of gout: report of six cases and review of the literature. Arch Intern Med. 1992;152(4):873-876. 7. Shukla R, Vender RB, Alhabeeb A, Salama S, Murphy F. Miliarial gout (a new entity). J Cutan Med Surg. 2007;11(1):31-34. 8. Niemi KM. Panniculitis of the legs with urate crystal deposition. Arch Dermatol. 1977;113(5):655-656. 9. Ochoa CD, Valderrama V, Mejia J, et al. Panniculitis: another clinical expression of gout. Rheumatol Int. 2011;31(6):831-835. 10. Dahiya A, Leach J, Levy H. Gouty panniculitis in a healthy male. J Am Acad Dermatol. 2007;57(2)(Suppl):S52-S54.
5. Koley S, Salodkar A, Choudhary S, Bhake A, Singhania K, Choudhury M. Tophi as first manifestation of gout. Indian J Dermatol Venereol Leprol. 2010;76(4):393-396.
JAMA Dermatology May 2014 Volume 150, Number 5
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/22/2015
jamadermatology.com
