MULTICENTRIC RETICULOHISTIOCYTOSIS- A RARE AND DISABLING DISEASE
Omowunmi Ashaolu1, Selwyn Ng2, Shaun
Smale3, Jenny Hughes1
1Clinical fellow, Department of Dermatology, Princess
of Wales Hospital, Bridgend, UK,
wunmi.ashaolu@wales.nhs.uk
2Consultant, Department of Histopathology, Morriston
Hospital, Swansea, UK,
selwyn.ng@wales.nhs.uk
3Consultant, Department of Rheumatology, Princess of
Wales Hospital, Bridgend UK,
shaun.smale@wales.nhs.uk
1Consultant, Department of Dermatology, Princess of
Wales Hospital, Bridgend, UK,
jenny.hughes@wales.nhs.uk.
A 39-year-old man presented with 5-week history of multiple discrete and
skin-coloured lesions on his hands, forearms, and face. He also had
severely painful, stiff, and swollen fingers. He was otherwise well with
no relevant personal or family history. Skin examination showed multiple
discrete and coalescing firm, reddish brown, tender papules of varying
sizes distributed mainly over the dorsum of the hands and nail folds
(Fig 1) with no mucosal involvement. There was bilateral swelling and
stiffness of the joints, especially the distal interphalangeal joints.
Baseline investigations, autoantibody, viral screen, and staging CT to
rule out underlying malignancy were normal. Radiographs of both hands
showed soft tissue swelling and subtle perierosions in the small joints
of the hands. Histopathology of the skin biopsy showed infiltration of
the dermis and subcutaneous fat by mononuclear and multinucleated
histiocytes with granular eosinophilic cytoplasm that showed positivity
for CD45, CD68 and factor 13a and negativity for S100- and CD1a (Fig 2).
Based on these findings a diagnosis of multicentric
reticulohistiocytosis was made.
He was initially treated with non-steroidal anti-inflammatory, Morphine,
Alendronate and Oral corticosteroids. With worsening disease activity,
Denosumab, oral methotrexate, hydroxychloroquine, infliximab,
tocilizumab and leflunomide were added sequentially, however there was
no symptom improvement. He was then considered for Tofacitinib 5mg twice
daily with improvement after 4 weeks of initiating this therapy
evidenced by improved sleep, skin symptoms and joint pains.
Multicentric reticulohistiocytosis is a rare, multisystem inflammatory
disease with unknown aetiology. It was first reported by Weber and
Freudenthal in 1937, however Goltz and Laymon coined the term
multicentric reticulohistiocytosis in 1954. Approximately 300 cases have
been reported in the literature with most from Europe and United States.
It is slightly predominant in women1 and symptoms
manifest from the fourth decade of life2. Associated
involvement of the joints impacts significantly on patients’ quality of
life due to limitations on activities of daily living which
inadvertently increases the risk of increased anxiety and depression.
The cause of MRH is not known but activated macrophages and increased
levels of TNF-alpha, IL-12, IL-1, and IL-63 have been
documented.
Cutaneous manifestation of MRH includes firm, discrete clustered reddish
brown to flesh-coloured papules or nodules that gradually enlarge in
size. It typically occurs over the joints of fingers and wrists giving a
characteristic coral bead appearance1 as seen in our
patient. Other commonly affected include the face giving leonine facies.
However any part of the body can be affected including
nail4 , mucosal surfaces1, lungs and
heart. Fever, weight loss and malaise have also been reported. In
addition, symmetrical polyarthritis mainly affecting the hands can
potentially progress to arthritis mutilans. Differential diagnosis
includes rheumatoid arthritis and psoriatic arthritis.
Although MRH is not a paraneoplastic disease, solid organ especially
breast and stomach carcinomas and haematological malignancies have been
reported in 31% of cases5 therefore underlying
malignancy should always be ruled out in a patient with MRH.
There is no laboratory test specific for MRH. Histological studies show
multinucleated giant cells with pale, fine, granular eosinophilic
cytoplasm in the dermis. Stains are negative for S100, CD34, factor
XIIIa and alpha-1-antitrypsin but positive for PAS and histiocytes
(vimentin, CD68, CD45 and MAC387)2. Langerhans
granules are absent on electron microscopy.
There are no established treatment guidelines owing to the rarity and
lack of controlled studies of the disease. The disease can be
self-limiting, however this may have caused severe joint destruction.
Prednisolone, immunomodulatory and disease modifying antirheumatic
drugs, TNF inhibitors either as monotherapies or combination therapies
have shown varying response. Tofacitinib, a selective JAK inhibitor,
licenced for the treatment of rheumatoid arthritis has also been
reported to be of benefit in the treatment of MRH6.
MRH is a rare disease that cause disfiguring skin lesions and disabling
arthritis therefore early recognition, and treatment is important to
prevent long term deformities. In conclusion, we present a patient with
a very rare non-Langerhans cell histiocytosis with typical clinical,
histopathological and immunohistochemical findings.
a
Fig 1: Showing coral bead appearance of multicentric
reticulohistiocytosis