Relationship between cutaneous polyarteritis nodosa (cPAN) and macular lymphocytic arteritis (MLA): Blinded histologic assessment of 35 cPAN cases

doi:10.1016/j.jaad.2015.09.010

Journal of the American Academy of Dermatology

Volume 73, Issue 6, December 2015, Pages 1013-1020

https://doi.org/10.1016/j.jaad.2015.09.010 Get rights and content

Background

Cutaneous polyarteritis nodosa (cPAN) is a skin medium vessel neutrophilic arteritis with livedo, nodules, and ulcerations. Macular lymphocytic arteritis (MLA) is a small arteritis with erythematous or pigmented macules and typical histologic features (a lymphocytic infiltrate, concentric fibrin ring, no disruption of the internal elastic lamina).

Objective

We sought to assess the frequency of clinical and histologic features of MLA in patients with cPAN.

Methods

This was a monocentric retrospective analysis of patients given the diagnosis of cPAN with blinded assessment of skin biopsy specimens.

Results

All 35 patients included had an infiltrated livedo, nodules, or both. Ulceration was rare. Erythematous or pigmented lesions were present in 54% of patients. Predominantly lymphocytic arteritis, a paucity of neutrophils, concentric fibrin ring, and absence of internal lamina elastic disruption were present in 60%, 20%, 18%, and 23% of patients, respectively. Median follow-up was 11 years. None of the patients had systemic involvement, and 57% had a complete remission. The incidence of complete remission was not different between patients having a predominant lymphocyte infiltrate or few neutrophils.

Limitations

This was a retrospective, monocentric study without a control group of patients with MLA.

Conclusions

Our data do not favor the classification of cPAN and MLA as distinct entities.

Section snippets

Methods

We queried the histopathological and clinical database of the Saint Louis Hospital, Paris, France, using the key word “cPAN” during the period from 1989 to 2013. Cases were included if they displayed: (1) a confirmed cPAN diagnosis after correlation of the clinical and histologic data according to previous definitions of cPAN (ie, typical cPAN skin symptoms, including livedo racemosa [corresponding to irregular broken segmented shapes with or without infiltration], and/or nodules, and/or

Results

In all, 35 patients with a diagnosis of cPAN were included in this study. The main demographic, clinical, biological, and histologic characteristics of the patients are summarized in Table I.

Discussion

After the initial description of MLA by Fein et al¹³ in 2003, 31 cases of MLA (including macular arteritis and lymphocytic thrombophilic arteritis) have been described in the literature to date.12, 13, 14, 16, 17, 18, 19, 20, 23, 24, 25, 26, 27, 28, 29, 30 Some authors suggest considering MLA to be an indolent variant of cPAN for the following reasons: (1) livedo racemosa (instead of pigmented macules) was found in 10 of 30 AML cases,14, 16, 17, 24, 25, 28 (2) ulceration or stellate ulceration

References (33)

P.-T. Chan et al.
Inflammatory plaque with peripheral nodules: a new specific finding of cutaneous polyarteritis nodosa
J Am Acad Dermatol
(2009)
H. Fein et al.
Cutaneous arteritis presenting with hyperpigmented macules: macular arteritis
J Am Acad Dermatol
(2003)
R. Valverde et al.
Macular arteritis: a pole of the spectrum of cutaneous polyarteritis nodosa?
Actas Dermo-Sifiliográficas
(2013)
C. Sadahira et al.
Macular arteritis in Japanese patients
J Am Acad Dermatol
(2005)
J.C. Jennette et al.
2012 Revised International Chapel Hill Consensus Conference nomenclature of vasculitides
Arthritis Rheum
(2013)
C. Pagnoux et al.
Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database
Arthritis Rheum
(2010)
N. Kluger et al.
French Vasculitis Study Group. Comparison of cutaneous manifestations in systemic polyarteritis nodosa and microscopic polyangiitis
Br J Dermatol
(2008)
K. Lindberg
Ein Beitrag zur Kenntnis der Periarteritis nodosa
Acta Med Scand
(1931)
D. Mimouni et al.
Cutaneous polyarteritis nodosa in patients presenting with atrophie blanche
Br J Dermatol
(2003)
M.S. Daoud et al.
Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases
Br J Dermatol
(1997)

J.L. Diaz-Perez et al.

Cutaneous periarteritis nodosa

Arch Dermatol

(1974)

T. Nakamura et al.

Cutaneous polyarteritis nodosa: revisiting its definition and diagnostic criteria

Arch Dermatol Res

(2009)

F. Furukawa

Cutaneous polyarteritis nodosa: an update

Ann Vasc Dis

(2012)

A.J. Morgan et al.

Cutaneous polyarteritis nodosa: a comprehensive review

Int J Dermatol

(2010)

Z. Saleh et al.

Macular lymphocytic arteritis: a unique benign cutaneous arteritis, mediated by lymphocytes and appearing as macules

J Cutan Pathol

(2009)

J.S.-S. Lee et al.

Lymphocytic thrombophilic arteritis: a newly described medium-sized vessel arteritis of the skin

Arch Dermatol

(2008)

Cited by (35)

Re: Letter from the Editor: Management of cutaneous polyarteritis nodosa
2023, Journal of the American Academy of Dermatology
Letter from the Editor: Management of cutaneous polyarteritis nodosa
2022, Journal of the American Academy of Dermatology
Updates in inflammatory dermatopathology
2022, Seminars in Diagnostic Pathology
Efficacy and safety of treatments in cutaneous polyarteritis nodosa: A French observational retrospective study
2022, Journal of the American Academy of Dermatology
Citation Excerpt :
Nonetheless, median treatment length for HCQ was only 1 month (IQR 1-3), but HCQ takes longer to work in most cases, so interpreting the primary outcome is difficult. GC monotherapy was often prescribed for cPAN in this study and in the literature.3,19,20 Nevertheless, Alibaz-Oner et al3 reported that more than 45% of cPAN patients experienced relapse after CR and that CR was never reached for 17% of patients, which underscores the need to add IS to achieve sustained CR.
Cutaneous polyarteritis nodosa is a form of medium-sized vessel vasculitis. Despite a disabling and prolonged course, data on treatment efficacy and safety remain scarce.
We aimed to describe treatment efficacy and safety in patients with cutaneous polyarteritis nodosa.
This multicenter retrospective, observational study, recorded clinical and biologic data together with treatments received. The primary outcome was the rate of complete response at month 3. Secondary outcomes assessed drug survival and safety.
We included 68 patients who received a median of 2 therapeutic lines (interquartile range, 1-3). Overall, complete response was achieved in 13 of 42 (31%) patients with colchicine, 4 of 17 (23%) with dapsone, 11 of 25 (44%) with glucocorticoids (GCs) alone, 1 of 9 (11%) with nonsteroidal anti-inflammatory drugs, 11 of 13 (84%) with GCs+azathioprine, and 7 of 15 (47%) with GCs+methotrexate. GCs+azathioprine had the best drug survival (median duration, 29.5 months; interquartile range, 19.5-36.0). Response at month 3 was decreased with peripheral neurologic involvement (odds ratio, 0.19; 95% confidence interval, 0.03-0.81; P = .04). Overall, the rate of treatment-related adverse events was 18%, which led to the discontinuation of treatment in 7% of patients.
Retrospective study.
Colchicine seems to confer good benefit-risk balance in cutaneous polyarteritis nodosa without peripheral sensory neuropathy. GCs+azathioprine seem the best treatment in the event of relapse.
Skin biopsies: their utility to allergists and immunologists
2022, Allergic and Immunologic Diseases: A Practical Guide to the Evaluation, Diagnosis and Management of Allergic and Immunologic Diseases
Skin biopsies are a commonly performed ancillary diagnostic test whose clinical utility may range from unnecessary to irreplaceably decisive, depending on the clinical setting and differential diagnosis. This chapter will review the diagnostic role of skin biopsy for eczematous and urticarial disorders most likely to be encountered by allergists/immunologists. The chapter is also a resource for rare autoinflammatory and immunodeficiency syndromes, and other skin disorders that may occasionally present to the allergy-immunology clinic.
Eczematous disorders include atopic dermatitis (eczema) but also other forms of eczematous dermatitis, including contact dermatitis, nummular dermatitis, seborrheic dermatitis, dyshidrosis, and others. On biopsy, these show a similar or identical appearance of spongiotic dermatitis, so clinical correlation is required to establish the final diagnosis.
Among urticarial disorders, the differential diagnosis of urticaria versus urticarial vasculitis represents a common indication for biopsy and may include direct immunofluorescence as an ancillary test that may increase diagnostic yield. Other urticarial disorders may include spongiotic/eczematous dermatitis, drug reactions, acquired immunobullous disorders, and a variety of rare autoinflammatory syndromes (chronic infantile neurologic cutaneous and articular disorder/neonatal-onset multisystem inflammatory disease, cryopyrin-associated periodic syndromes, familial cold autoinflammatory syndrome, hereditary angioedema, Muckle–Wells syndrome, NLRP12-associated autoinflammatory disease, Schnitzler syndrome). While histology alone can potentially establish a diagnosis of vasculitis or exclude a diagnosis of urticaria, in other cases, such as drug reactions, clinical correlation is always required.
Autoinflammatory and immunodeficiency are exceptionally rare. While histopathologic features alone are not diagnostic, recurring histologic reaction patterns have been observed and may be helpful in narrowing the differential diagnosis or supporting a suspected diagnosis. Noninfectious cutaneous granulomas may occur in ataxia-telangiectasia, Blau syndrome, chronic granulomatous disease, combined immunodeficiency, common variable immunodeficiency, Good syndrome, hemophagocytic lymphohistiocytosis, PLCγ2-associated antibody deficiency and immune dysregulation, primary biliary cirrhosis, severe CID, and X-linked agammaglobulinemia.
Lymphocytic thrombophilic arteritis with lower-limb ulcers
2021, Anais Brasileiros de Dermatologia
Lymphocytic thrombophilic arteritis is a recently described entity, histopathologically characterized by lymphocytic vasculitis that affects the arterioles of the dermo-hypodermic junction, associated with deposition of fibrin and a luminal fibrin ring. A 49-year-old female patient presented with achromic maculae and a well-defined ulcer on the medial aspect of the left lower limb. The biopsy showed intense inflammatory infiltrate in the papillary dermis with a predominance of lymphocytes, and medium-caliber vessels surrounded by mononuclear infiltrates in the deep reticular dermis. Masson’s trichrome staining showed intense destruction of the muscle layer of the vascular wall and a fibrin ring. Good clinical response was attained with azathioprine. The authors believe that the ulceration might be another clinical presentation or represent an atypical progression of this condition.

View all citing articles on Scopus

: Funding sources: None.

: Drs Buffiere-Morgado and Battistella have equally contributed to this work and share first authorship.

: Conflicts of interest: None declared.

View full text

Original articleRelationship between cutaneous polyarteritis nodosa (cPAN) and macular lymphocytic arteritis (MLA): Blinded histologic assessment of 35 cPAN cases

Background

Objective

Methods

Results

Limitations

Conclusions

Section snippets

Methods

Results

Discussion

J Am Acad Dermatol

J Am Acad Dermatol

Actas Dermo-Sifiliográficas

J Am Acad Dermatol

2012 Revised International Chapel Hill Consensus Conference nomenclature of vasculitides

Arthritis Rheum

Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database

Arthritis Rheum

French Vasculitis Study Group. Comparison of cutaneous manifestations in systemic polyarteritis nodosa and microscopic polyangiitis

Br J Dermatol

Ein Beitrag zur Kenntnis der Periarteritis nodosa

Acta Med Scand

Cutaneous polyarteritis nodosa in patients presenting with atrophie blanche

Br J Dermatol

Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases

Br J Dermatol

Cutaneous periarteritis nodosa

Arch Dermatol

Cutaneous polyarteritis nodosa: revisiting its definition and diagnostic criteria

Arch Dermatol Res

Cutaneous polyarteritis nodosa: an update

Ann Vasc Dis

Cutaneous polyarteritis nodosa: a comprehensive review

Int J Dermatol

Macular lymphocytic arteritis: a unique benign cutaneous arteritis, mediated by lymphocytes and appearing as macules

J Cutan Pathol

Lymphocytic thrombophilic arteritis: a newly described medium-sized vessel arteritis of the skin

Arch Dermatol

Original article
Relationship between cutaneous polyarteritis nodosa (cPAN) and macular lymphocytic arteritis (MLA): Blinded histologic assessment of 35 cPAN cases