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PubMed This is a summary of 19 peer-reviewed journal articles Updated
Rheumatology

Symptoms and Subtypes: Systemic vs. Cutaneous PAN

At a Glance

Polyarteritis nodosa (PAN) is divided into cutaneous PAN, which affects only the skin, and systemic PAN, which involves internal organs and nerves. Distinguishing between them and ruling out genetic mimics like DADA2 is critical for determining the correct treatment plan.

Polyarteritis nodosa (PAN) is not a one-size-fits-all condition. It is categorized into two main forms: Systemic PAN, which can affect multiple organs throughout the body, and Cutaneous PAN, which is primarily limited to the skin [1][2]. Understanding which subtype you have is essential for determining the right level of treatment and monitoring.

Systemic vs. Cutaneous PAN

While both types involve the same kind of blood vessel inflammation (necrotizing vasculitis), they affect the body very differently:

  • Cutaneous PAN (cPAN): This form is localized to the skin. It commonly presents with livedo racemosa (a persistent, purple, lace-like pattern on the skin) and palpable nodules (painful lumps under the skin, often on the legs) [3][2]. While cPAN can be chronic and may relapse, it rarely progresses to affect internal organs [4][1]. Because it is less severe, cPAN is often treated with milder medications—such as colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), or moderate doses of steroids—rather than the heavy immunosuppressants used for systemic PAN [2].
  • Systemic PAN (sPAN): This is a more severe form that involves internal organs such as the kidneys, heart, and gastrointestinal tract [5]. Common symptoms include severe abdominal pain, high blood pressure, and significant weight loss [5][6].

Understanding Mononeuritis Multiplex

One of the most telling signs of systemic PAN is a specific type of nerve damage called mononeuritis multiplex [7].

Unlike general “numbness,” mononeuritis multiplex occurs when inflammation cuts off the blood supply to specific, individual nerves in different parts of the body [7][8]. It often manifests as:

  • Foot Drop or Wrist Drop: Sudden weakness that makes it difficult to lift your foot or hand [9][8].
  • Asymmetrical Symptoms: You might feel severe pain or numbness in your right foot and your left hand simultaneously [7].
  • Sharp, “Electrical” Pain: Intense nerve pain that follows the path of a specific nerve [9].

The presence of these neurological symptoms is often a signal that the disease has moved beyond the skin and requires more intensive systemic treatment [8][10].

DADA2: The Genetic “Mimic”

In recent years, researchers have identified a genetic condition called DADA2 (Deficiency of Adenosine Deaminase 2) that can look exactly like PAN [11][12].

DADA2 is caused by a mutation in the ADA2 gene and often begins in childhood [11]. It is a critical diagnosis to distinguish from classic PAN for several reasons:

  • Stroke Risk: People with DADA2 have a high risk of early-onset lacunar strokes (strokes caused by damage to small arteries in the brain), which are much less common in classic PAN [13][14].
  • Different Treatment: While classic PAN is often treated with heavy chemotherapy-like drugs or steroids, DADA2 responds remarkably well to TNF inhibitors (a type of biologic therapy) [15][16]. These medications can be life-saving and are highly effective at preventing future strokes in DADA2 patients [17][18].

If you were diagnosed with PAN at a young age or have a family history of early strokes, your doctor may recommend genetic testing for the ADA2 gene to ensure you are receiving the most effective therapy [12][19].

Common questions in this guide

What is the difference between cutaneous and systemic PAN?
Cutaneous PAN affects only the blood vessels in the skin, causing lumps or a lace-like purple rash. Systemic PAN is a more severe form that inflames vessels in internal organs and nerves, requiring stronger medications to prevent organ damage.
What does mononeuritis multiplex mean for my PAN?
Mononeuritis multiplex is a specific type of nerve damage caused when inflammation blocks blood flow to individual nerves. It often causes sudden asymmetrical weakness, like foot drop or wrist drop, or sharp electrical pain, signaling that PAN is affecting the nervous system.
What is DADA2 and how does it relate to PAN?
DADA2 is a rare genetic condition that closely mimics the symptoms of PAN but carries a high risk of early-onset strokes. It is caused by a mutation in the ADA2 gene and is typically diagnosed in childhood or in people with a family history of early strokes.
Why does it matter if I have DADA2 instead of classic PAN?
Classic PAN is generally treated with strong immunosuppressants or steroids, but DADA2 does not respond well to these drugs. Instead, DADA2 is highly responsive to biologic therapies called TNF inhibitors, which can be life-saving and prevent future strokes.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Do my current symptoms, such as the skin nodules or livedo racemosa, suggest Cutaneous PAN or the systemic form of the disease?
  2. 2.I've noticed some numbness and 'foot drop'—could this be mononeuritis multiplex, and what does that mean for my treatment plan?
  3. 3.Given the rarity of PAN, should I be screened for the ADA2 genetic mutation (DADA2), especially if there is a history of early strokes in my family?
  4. 4.If my diagnosis is DADA2 rather than classic PAN, how would my treatment change? For example, would I start on a TNF inhibitor?

Questions For You

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References

References (19)
  1. 1

    An update on the nomenclature for cutaneous vasculitis.

    Caproni M, Verdelli A

    Current opinion in rheumatology 2019; (31(1)):46-52 doi:10.1097/BOR.0000000000000563.

    PMID: 30394939
  2. 2

    [Cutaneous alterations in vasculitides : Part 2: Special aspects of diseases of large, medium and small vessels].

    Sunderkötter C, Michl C

    Der Internist 2019; (60(8)):805-813 doi:10.1007/s00108-019-0642-3.

    PMID: 31300830
  3. 3

    Manifestations, clinical course and prognostic markers in cutaneous polyarteritis nodosa.

    Munera-Campos M, Bielsa I, Martínez-Morillo M, et al.

    Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG 2020; (18(11)):1250-1259 doi:10.1111/ddg.14271.

    PMID: 33015940
  4. 4

    Refractory cutaneous polyarteritis nodosa: Successful treatment with etanercept.

    Inoue N, Shimizu M, Mizuta M, et al.

    Pediatrics international : official journal of the Japan Pediatric Society 2017; (59(6)):751-752 doi:10.1111/ped.13283.

    PMID: 28626974
  5. 5

    Putting the Pieces Into Place: A Case of Systemic Polyarteritis Nodosa.

    Brodell D, Scott G, Plovanich M

    Cureus 2020; (12(6)):e8442 doi:10.7759/cureus.8442.

    PMID: 32642356
  6. 6

    Case Report: Polyarteritis nodosa or complicated Henoch-Schonlein purpura (IgAV), a rare case.

    Hasanzadeh S, Alavi SM, Masnavi E, et al.

    F1000Research 2018; (7()):49 doi:10.12688/f1000research.13295.2.

    PMID: 29770208
  7. 7

    Spontaneous accessory renal artery aneurysm rupture as a first presentation of polyarteritis nodosa: a case report and review of literature.

    Amro RN, Maraqa L, Abo Jheasha AA, et al.

    Annals of medicine and surgery (2012) 2025; (87(6)):3956-3962 doi:10.1097/MS9.0000000000003331.

    PMID: 40486591
  8. 8

    A Case of Challenging Polyarteritis Nodosa With Critical Limb Ischemia.

    Renken L, Zollinger-Read C, Coote A

    Cureus 2025; (17(11)):e97257 doi:10.7759/cureus.97257.

    PMID: 41426900
  9. 9

    An 80-year-old female with multiple mononeuropathy: neuroleukemiosis a rare complication of chronic lymphocytic leukaemia.

    Morgan C, Srinivasan V, Pohl U, Wakerley BR

    Oxford medical case reports 2025; (2025(8)):omaf131 doi:10.1093/omcr/omaf131.

    PMID: 40809163
  10. 10

    Mononeuritis multiplex in a patient with cutaneous arteritis diagnosed by skin biopsy.

    Isahaya K, Shiraishi M, Tanaka K, et al.

    Rinsho shinkeigaku = Clinical neurology 2017; (57(6)):307-310 doi:10.5692/clinicalneurol.cn-001013.

    PMID: 28552872
  11. 11

    Deficiency of adenosine deaminase 2 (DADA2): Review.

    Sharma V, Deo P, Sharma A

    Best practice & research. Clinical rheumatology 2023; (37(1)):101844 doi:10.1016/j.berh.2023.101844.

    PMID: 37328410
  12. 12

    Expanding spectrum of DADA2: a review of phenotypes, genetics, pathogenesis and treatment.

    Pinto B, Deo P, Sharma S, et al.

    Clinical rheumatology 2021; (40(10)):3883-3896 doi:10.1007/s10067-021-05711-w.

    PMID: 33791889
  13. 13

    Central retinal artery occlusion in a child with ADA2 deficiency: a case report.

    Sharabati I, Ayesh BM, Qafesha RM, et al.

    Annals of medicine and surgery (2012) 2024; (86(4)):2343-2347 doi:10.1097/MS9.0000000000001857.

    PMID: 38576931
  14. 14

    Sequential central retinal artery occlusion in two brothers: a fight to prevent blindness.

    Oliver-Gutierrez D, Subirà O, Zabalza A, et al.

    Documenta ophthalmologica. Advances in ophthalmology 2025; (150(2)):105-110 doi:10.1007/s10633-025-10006-5.

    PMID: 39934596
  15. 15

    Pediatric-Onset Polyarteritis Nodosa and Deficiency of Adenosine Deaminase 2: Clinical Overlap and Divergence.

    Atamyildiz Uçar S, Tunce E, Türkmen Ş, et al.

    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 2025; (31(8)):299-305 doi:10.1097/RHU.0000000000002270.

    PMID: 40815801
  16. 16

    TNF inhibition in vasculitis management in adenosine deaminase 2 deficiency (DADA2).

    Deuitch NT, Yang D, Lee PY, et al.

    The Journal of allergy and clinical immunology 2022; (149(5)):1812-1816.e6 doi:10.1016/j.jaci.2021.10.030.

    PMID: 34780847
  17. 17

    Anti-tumour necrosis factor treatment for the prevention of ischaemic events in patients with deficiency of adenosine deaminase 2 (DADA2).

    Cooray S, Omyinmi E, Hong Y, et al.

    Rheumatology (Oxford, England) 2021; (60(9)):4373-4378 doi:10.1093/rheumatology/keaa837.

    PMID: 33420503
  18. 18

    Hepatic Manifestations and Response to Treatment in Deficiency of Adenosine Deaminase 2.

    Shaik MR, Alao H, Shaik NA, et al.

    Liver international : official journal of the International Association for the Study of the Liver 2026; (46(6)):e70660 doi:10.1111/liv.70660.

    PMID: 42083127
  19. 19

    Cutaneous Manifestations of Medium- and Large-Vessel Vasculitis.

    Chasset F, Francès C

    Clinical reviews in allergy & immunology 2017; (53(3)):452-468 doi:10.1007/s12016-017-8612-9.

    PMID: 28547523

This page explains Polyarteritis Nodosa (PAN) symptoms and subtypes for informational purposes only. Always consult a rheumatologist or vascular specialist for an accurate diagnosis, genetic testing, and treatment plan.

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