Clinicopathologic challenge
Acute rash and ankle pain in a young woman Mary Grace Baker1, BA, Michael A. Marchetti2, MD, James W. Patterson3, MD, and Thomas G. Cropley2, MD
1 School of Medicine, University of Virginia, Charlottesville, VA, USA, 2Department of Dermatology, University of Virginia, Charlottesville, VA, USA, and 3Department of Pathology, University of Virginia, Charlottesville, VA, USA
Correspondence Thomas G. Cropley, MD Department of Dermatology University of Virginia PO Box 800718 Charlottesville VA 22908 USA E-mail: [email protected] Conflicts of interest: None.
History A 22-year-old African-American woman was referred to our dermatology department from a teen health clinic for a 1-day history of rash and severe ankle pain. The patient had been in excellent health with no pertinent past medical history until the emergence of red blotches on her hands the previous night and the subsequent development of chills, skin bumps, and difficulty in ambulation. On physical examination, the patient was found to be afebrile
Figure 1 Clinical examination in a 22-year-old woman shows erythema and swelling of the left second metacarpophalangeal joint ª 2014 The International Society of Dermatology
What is your diagnosis?
(a)
(b) Figure 2 Clinical examination in the same patient shows (a) an erythematous macule with early pustule formation on the lateral right palm, and (b) a solitary pustule on the left lateral leg
(a)
(b)
Figure 3 (a) Low-power inspection of the histopathology of the left ankle biopsy shows a perivascular dermal infiltrate. Within the mid-dermis, an occluded vessel can be identified, infiltrated by lymphocytes and neutrophils. (b) Higher-power inspection demonstrates a thrombosed/occluded vessel permeated by neutrophils. [Hematoxylin and eosin stain; original magnification (a) 9 40; (b) 9 100]
Figure 4 Gram stain demonstrates the presence of Gramnegative diplococci within the thrombus. (Gram stain; original magnification 31000) International Journal of Dermatology 2014, 53, 1183–1185
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Clinicopathologic challenge
Rash and arthralgias
but appeared unwell with rigors. Palpation and manipulation of the left ankle elicited severe tenderness. Cutaneous inspection revealed swelling of the left second metacarpal joint with overlying erythema (Fig. 1), subtle erythematous macules with early pustule formation on the palms bilaterally (Fig. 2a), and rare, tiny, red papules and pustules on the wrists, ankles, and legs (Fig. 2b). The patient denied any recent travel, exposure to sick contacts, or arthropod bites. Her last sexual encounter had taken place five weeks prior to presentation, and she denied dysuria, pelvic pain, and vaginal discharge. There was no family history of any rheumatologic or autoimmune disease. A skin biopsy of a papule overlying the left ankle was performed and submitted for histopathologic examination (Fig. 3). Diagnosis Disseminated gonococcal infection (DGI). Discussion With clinical concern for disseminated gonococcal infection, the patient was referred to the emergency department for further workup and inpatient admission. A pelvic examination demonstrated cervical motion tenderness and purulent discharge, despite the patient’s reported negative symptoms. An endocervical swab was submitted for polymerase chain reaction (PCR) amplification of Neisseria gonorrhoeae and Chlamydia trachomatis nucleic acids and confirmed infection with N. gonorrhoeae. Blood cultures and cerebrospinal fluid analysis and culture were unremarkable. Histopathologic examination of the skin biopsy revealed a thrombosed and occluded dermal blood vessel permeated by neutrophils, consistent with septic vasculitis (Fig. 3). Gram stain showed Gramnegative diplococci within the intraluminal thrombus (Fig. 4). The characteristic clinical presentation, positive N. gonorrhoeae PCR testing, and cutaneous histopathology all supported a diagnosis of DGI. Disseminated gonococcal infection, sometimes referred to as arthritis–dermatitis syndrome, classically presents as a triad of rash, non-purulent arthritis, and tenosynovitis.1,2 Less commonly, patients may present with only pyogenic arthritis. As the prevalence of gonorrhea has decreased to historically low levels in the USA, DGI has become increasingly rare. Nevertheless, there are approximately 700,000 annual cases of gonorrhea in the USA, and estimates suggest that 1–3% of adults who become infected with gonorrhea may develop DGI.3,4 Risk factors for systemic dissemination include congenital or acquired terminal complement deficiency (C5–C9), systemic lupus erythematosus, history of pelvic surgery, recent intrauterInternational Journal of Dermatology 2014, 53, 1183–1185
Baker et al.
ine device insertion, current pregnancy, and recent menses.2,5,6 The greatest risk for dissemination is within 2– 3 weeks of primary urogenital infection or within one week of menstruation. Patients are typically asymptomatic at the site of the primary infection.2,4,5 Although constitutional symptoms may include fever and chills, up to 40% of patients are afebrile.5 Cutaneous manifestations of DGI are reported in 60– 75% of cases.2,5 Lesions preferentially affect the extremities and begin as painless macules, petechiae, or papules.2 Over time, lesions evolve into pustules with gunmetal gray necrotic centers on a hemorrhagic base. Bacterial embolization and microabscess formation have been implicated in the pathogenesis of cutaneous disease, and, as in the patient presented, bacteria can occasionally be visualized in biopsy specimens. Other uncommonly reported presentations include vesicles and bullae or nonspecific and probably immunologically mediated phenomena such as erythema nodosum, erythema multiforme, and urticaria.5 Polyarthralgia or arthritis are reported in 52–99% of patients, most often involving the knees, elbows, wrists, ankles, and interphalangeal joints.1,4,5 Tenosynovitis of the wrists, fingers, toes, and ankles is estimated to affect up to 68% of patients.5 Rare complications of DGI include endocarditis, meningitis, perihepatitis, osteomyelitis, and epidural abscess.1,3,5 Given its heterogeneous clinical presentation and frequent lack of a symptomatic primary infection, DGI may not be initially recognized. A broad differential diagnosis may include other infectious etiologies that lead to bacterial or fungal hematogeneous dissemination to the skin, acute viral infections (human immunodeficiency virus [HIV] and hepatitis B virus [HBV]), Lyme disease, drug reactions (particularly erythema multiforme), acute rheumatoid arthritis, Behcßet’s disease, reactive arthritis, bowel-associated dermatitis–arthritis syndrome, leukocytoclastic vasculitis, systemic lupus erythematosus, and polyarteritis nodosa. In patients with suspected DGI, a complete history and physical examination should be performed and should include a pelvic examination. Swabs from all possible sites of primary infection should be submitted for Gram stain, bacterial culture, and PCR amplification of N. gonorrhoeae. In individual clinical scenarios, joint aspiration for microscopic analysis and culture, and skin lesion biopsy may be diagnostically useful. With prompt recognition and treatment, the prognosis for patients with DGI is favorable. First-line therapy is IV ceftriaxone 1 g/day, with conversion to oral cefixime 400 mg twice per day after 24–48 hours of improvement on IV antibiotics.3 Empiric treatment of C. trachomatis with oral azithromycin 1 g is recommended. Patients with recurrent disease should be screened for terminal ª 2014 The International Society of Dermatology
Baker et al.
complement pathway deficiencies (C5–C9).5 The patient presented began empiric therapy with IV ceftriaxone in the emergency department and experienced symptomatic improvement within 24 hours. She was converted to oral cefuroxime 1 g twice per day and discharged on hospital day 4, having made a full recovery. References 1 Bleich AT, Sheffield JS, Wendel GD, et al. Disseminated gonococcal infection in women. Obstet Gynecol 2012; 119: 597–602. 2 Brown TJ, Yen-Moore A, Tyring SK. An overview of sexually transmitted diseases. Part 1. J Am Acad Dermatol 1999; 41: 511–529.
ª 2014 The International Society of Dermatology
Rash and arthralgias
Clinicopathologic challenge
3 Workowski KA, Berman S; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines,2010. MMWR Recomm Rep 2010; 59: 1–116. 4 Miller KE. Diagnosis and treatment of Neisseria gonorrhoeae infections. Am Fam Physician 2006; 73: 1779–1784. 5 Rice PA. Gonococcal arthritis (disseminated gonococcal infection). Infect Dis Clin North Am 2005; 19: 853–861. 6 Mitchell SR, Nguyen PQ, Katz P. Increased risk of neisserial infections in systemic lupus erythematosus. Semin Arthritis Rheum 1990; 20: 174–184.
International Journal of Dermatology 2014, 53, 1183–1185
1185
Acute rash and ankle pain in a young woman Mary Grace Baker1, BA, Michael A. Marchetti2, MD, James W. Patterson3, MD, and Thomas G. Cropley2, MD
1 School of Medicine, University of Virginia, Charlottesville, VA, USA, 2Department of Dermatology, University of Virginia, Charlottesville, VA, USA, and 3Department of Pathology, University of Virginia, Charlottesville, VA, USA
Correspondence Thomas G. Cropley, MD Department of Dermatology University of Virginia PO Box 800718 Charlottesville VA 22908 USA E-mail: [email protected] Conflicts of interest: None.
History A 22-year-old African-American woman was referred to our dermatology department from a teen health clinic for a 1-day history of rash and severe ankle pain. The patient had been in excellent health with no pertinent past medical history until the emergence of red blotches on her hands the previous night and the subsequent development of chills, skin bumps, and difficulty in ambulation. On physical examination, the patient was found to be afebrile
Figure 1 Clinical examination in a 22-year-old woman shows erythema and swelling of the left second metacarpophalangeal joint ª 2014 The International Society of Dermatology
What is your diagnosis?
(a)
(b) Figure 2 Clinical examination in the same patient shows (a) an erythematous macule with early pustule formation on the lateral right palm, and (b) a solitary pustule on the left lateral leg
(a)
(b)
Figure 3 (a) Low-power inspection of the histopathology of the left ankle biopsy shows a perivascular dermal infiltrate. Within the mid-dermis, an occluded vessel can be identified, infiltrated by lymphocytes and neutrophils. (b) Higher-power inspection demonstrates a thrombosed/occluded vessel permeated by neutrophils. [Hematoxylin and eosin stain; original magnification (a) 9 40; (b) 9 100]
Figure 4 Gram stain demonstrates the presence of Gramnegative diplococci within the thrombus. (Gram stain; original magnification 31000) International Journal of Dermatology 2014, 53, 1183–1185
1183
1184
Clinicopathologic challenge
Rash and arthralgias
but appeared unwell with rigors. Palpation and manipulation of the left ankle elicited severe tenderness. Cutaneous inspection revealed swelling of the left second metacarpal joint with overlying erythema (Fig. 1), subtle erythematous macules with early pustule formation on the palms bilaterally (Fig. 2a), and rare, tiny, red papules and pustules on the wrists, ankles, and legs (Fig. 2b). The patient denied any recent travel, exposure to sick contacts, or arthropod bites. Her last sexual encounter had taken place five weeks prior to presentation, and she denied dysuria, pelvic pain, and vaginal discharge. There was no family history of any rheumatologic or autoimmune disease. A skin biopsy of a papule overlying the left ankle was performed and submitted for histopathologic examination (Fig. 3). Diagnosis Disseminated gonococcal infection (DGI). Discussion With clinical concern for disseminated gonococcal infection, the patient was referred to the emergency department for further workup and inpatient admission. A pelvic examination demonstrated cervical motion tenderness and purulent discharge, despite the patient’s reported negative symptoms. An endocervical swab was submitted for polymerase chain reaction (PCR) amplification of Neisseria gonorrhoeae and Chlamydia trachomatis nucleic acids and confirmed infection with N. gonorrhoeae. Blood cultures and cerebrospinal fluid analysis and culture were unremarkable. Histopathologic examination of the skin biopsy revealed a thrombosed and occluded dermal blood vessel permeated by neutrophils, consistent with septic vasculitis (Fig. 3). Gram stain showed Gramnegative diplococci within the intraluminal thrombus (Fig. 4). The characteristic clinical presentation, positive N. gonorrhoeae PCR testing, and cutaneous histopathology all supported a diagnosis of DGI. Disseminated gonococcal infection, sometimes referred to as arthritis–dermatitis syndrome, classically presents as a triad of rash, non-purulent arthritis, and tenosynovitis.1,2 Less commonly, patients may present with only pyogenic arthritis. As the prevalence of gonorrhea has decreased to historically low levels in the USA, DGI has become increasingly rare. Nevertheless, there are approximately 700,000 annual cases of gonorrhea in the USA, and estimates suggest that 1–3% of adults who become infected with gonorrhea may develop DGI.3,4 Risk factors for systemic dissemination include congenital or acquired terminal complement deficiency (C5–C9), systemic lupus erythematosus, history of pelvic surgery, recent intrauterInternational Journal of Dermatology 2014, 53, 1183–1185
Baker et al.
ine device insertion, current pregnancy, and recent menses.2,5,6 The greatest risk for dissemination is within 2– 3 weeks of primary urogenital infection or within one week of menstruation. Patients are typically asymptomatic at the site of the primary infection.2,4,5 Although constitutional symptoms may include fever and chills, up to 40% of patients are afebrile.5 Cutaneous manifestations of DGI are reported in 60– 75% of cases.2,5 Lesions preferentially affect the extremities and begin as painless macules, petechiae, or papules.2 Over time, lesions evolve into pustules with gunmetal gray necrotic centers on a hemorrhagic base. Bacterial embolization and microabscess formation have been implicated in the pathogenesis of cutaneous disease, and, as in the patient presented, bacteria can occasionally be visualized in biopsy specimens. Other uncommonly reported presentations include vesicles and bullae or nonspecific and probably immunologically mediated phenomena such as erythema nodosum, erythema multiforme, and urticaria.5 Polyarthralgia or arthritis are reported in 52–99% of patients, most often involving the knees, elbows, wrists, ankles, and interphalangeal joints.1,4,5 Tenosynovitis of the wrists, fingers, toes, and ankles is estimated to affect up to 68% of patients.5 Rare complications of DGI include endocarditis, meningitis, perihepatitis, osteomyelitis, and epidural abscess.1,3,5 Given its heterogeneous clinical presentation and frequent lack of a symptomatic primary infection, DGI may not be initially recognized. A broad differential diagnosis may include other infectious etiologies that lead to bacterial or fungal hematogeneous dissemination to the skin, acute viral infections (human immunodeficiency virus [HIV] and hepatitis B virus [HBV]), Lyme disease, drug reactions (particularly erythema multiforme), acute rheumatoid arthritis, Behcßet’s disease, reactive arthritis, bowel-associated dermatitis–arthritis syndrome, leukocytoclastic vasculitis, systemic lupus erythematosus, and polyarteritis nodosa. In patients with suspected DGI, a complete history and physical examination should be performed and should include a pelvic examination. Swabs from all possible sites of primary infection should be submitted for Gram stain, bacterial culture, and PCR amplification of N. gonorrhoeae. In individual clinical scenarios, joint aspiration for microscopic analysis and culture, and skin lesion biopsy may be diagnostically useful. With prompt recognition and treatment, the prognosis for patients with DGI is favorable. First-line therapy is IV ceftriaxone 1 g/day, with conversion to oral cefixime 400 mg twice per day after 24–48 hours of improvement on IV antibiotics.3 Empiric treatment of C. trachomatis with oral azithromycin 1 g is recommended. Patients with recurrent disease should be screened for terminal ª 2014 The International Society of Dermatology
Baker et al.
complement pathway deficiencies (C5–C9).5 The patient presented began empiric therapy with IV ceftriaxone in the emergency department and experienced symptomatic improvement within 24 hours. She was converted to oral cefuroxime 1 g twice per day and discharged on hospital day 4, having made a full recovery. References 1 Bleich AT, Sheffield JS, Wendel GD, et al. Disseminated gonococcal infection in women. Obstet Gynecol 2012; 119: 597–602. 2 Brown TJ, Yen-Moore A, Tyring SK. An overview of sexually transmitted diseases. Part 1. J Am Acad Dermatol 1999; 41: 511–529.
ª 2014 The International Society of Dermatology
Rash and arthralgias
Clinicopathologic challenge
3 Workowski KA, Berman S; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines,2010. MMWR Recomm Rep 2010; 59: 1–116. 4 Miller KE. Diagnosis and treatment of Neisseria gonorrhoeae infections. Am Fam Physician 2006; 73: 1779–1784. 5 Rice PA. Gonococcal arthritis (disseminated gonococcal infection). Infect Dis Clin North Am 2005; 19: 853–861. 6 Mitchell SR, Nguyen PQ, Katz P. Increased risk of neisserial infections in systemic lupus erythematosus. Semin Arthritis Rheum 1990; 20: 174–184.
International Journal of Dermatology 2014, 53, 1183–1185
1185
