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J Ayub Med Coll Abbottabad 2023;35(2)
316
CASE REPORT
MULTICENTRIC RETICULOHISTIOCYTOSIS (MRH):
A CASE REPORT ON A RARE DESTRUCTIVE ARTHRITIS
Saira Bano1, Tayyeba Khursheed1, Mohammad Khalid Bosan2, Sadia Khurshid1
1Department of Rheumatology, Pakistan Institute of Medical Sciences, Islamabad, 2Pakistan Atomic Energy Hospital, Islamabad-Pakistan
Multicentric Reticulohistiocytosis is a rare disorder of unknown aetiology which affects skin and joints
predominantly. There are no specific laboratory investigations for diagnosis. Diagnosis can be made
clinically and on a histopathological basis. There is no consensus on treatment. We report a case from
Pakistan with classical presentation who did well on methotrexate and low dose steroids. Prompt
diagnosis and early treatment may save from significant disability.
Keywords: Multicentric Reticulohistiocytosis; MRH; Arthritis; Inflammatory arthritis; Citation
Citation: Bano S, Khursheed T, Bosan MK, Khurshid S. Multicentric Reticulohistiocytosis (MRH): A Case report
on a rare destructive arthritis. J Ayub Med Coll Abbottabad 2023;35(2):316–9.
DOI: 10.55519/JAMC-02-9261
INTRODUCTION
Multicentric Reticulohistiocytosis (MRH) is an
extraordinarily rare multisystem disorder of
undetermined aetiology. It usually affects
Caucasian females in their 50s. Clinically it is
recognized by a combination of symmetric erosive
polyarthritis and characteristic papulo-nodular skin
lesions.1 Its prevalence is unknown. Only a few
hundred cases have been reported in the literature,
are mostly from Western countries. Arthritis
described in the literature is mostly symmetrical,
erosive, affecting the joints of hands, elbows,
knees and shoulders. In hands the distal joints
maybe predominantly involved, helping to
differentiate it from rheumatoid arthritis. If left
untreated it may become progressively destructive.
Arthritis mutilans has been described in 45% of the
cases.2 The classical skin eruptions are red to
brown in colour and in the form of papules and
nodules. The lesions typically appear on the face,
hands, dorsal aspects of small joints and
elsewhere. The lesions may coalesce to give an
appearance, which is described as coral beads or
strings of pearls.3 Malignancy has been reported in
up to a quarter of cases.4 We report a case of
Multicentric Reticulohistiocytosis in a Pakistani
man who presented with classical findings.
CASE REPORT
A 64-year-old Pakistani man with no previously
known co-morbidities presented to our clinic with
complaints of painful joints and extensive skin
rash. His problems started two years ago when
reddish bumps started appearing on his hands,
elbows, scalps, back and thighs. These bumps were
not painful or itchy. The rash would spontaneously
resolve and recur. Months later, the patient
developed pain in multiple joints, which was
associated with swelling and early morning
stiffness for more than one hour. Affected joints
included small joints of hands, elbows, shoulders,
knees and ankles. He also reported subjective
fever and undocumented weight loss.
On examination, multiple red-brown
macules and papules were observed in a
symmetrical fashion over the dorsum of hands,
elbows, around the ears, along the neck, the back
and thighs. Musculoskeletal examination revealed
swelling and tenderness in the proximal and distal
interphalangeal joints, metacarpophalangeal joints,
elbows, shoulders, knees and ankles. The rest of
the systemic examination was unremarkable.
Investigations revealed normal Complete blood
count, liver and muscles enzymes and renal
function tests. ESR was elevated (85 mm/hour).
Rheumatoid arthritis (RA) factor, Anti-
citrullinated peptide antibodies (anti-CCP), anti-
nuclear antibodies (ANA), and extractable nuclear
antibodies (ENA) were negative. Initial
differentials included rheumatoid arthritis,
dermatomyositis and carcinomatous arthritis.
Skin biopsy revealed dense infiltrate in the
dermis laden by histiocytes and multinucleated giant
cells. Mild to moderate amount of lymphocytic
infiltrate was scattered around the giant cells. X-ray of
the hand revealed erosive changes in the left carpus
and right second proximal interphalangeal join (PIP).
On clinical grounds and histopathology of the skin
specimen, a diagnosis of MRH was made. Patient was
started on low dose prednisolone (7.5 mg/ day) and
low dose methotrexate (7.5 mg/ week). An extensive
workup to rule out an underlying malignancy was
done. As malignancy could not be detected patient was
discharged and followed up. Arthritis resolved in three
months and skin rashes improved on subsequent visits.
J Ayub Med Coll Abbottabad 2023;35(2)
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Figure-1: (A) and (B). Typical papulo-nodular eruption over elbow and at the back of neck giving coral bead
appearance.
Figure-2: Rheumatoid arthritis like deformities affecting the hand. Figure-3: Radiographs of the hand
showing erosions in the carpal and carpometacarpal joints.
DISCUSSION
This case report was written to create awareness
about the clinical spectrum of MRH as knowledge
about the disease and its outcomes are limited. It is
rare and the number of cases described in the
literature, do not exceed a few hundred. Furthermore,
our review of the literature suggests most cases being
reported from Western countries and amongst the
white population. Worldwide, most cases report a
Caucasian predominance.5 The reason could be
increased awareness and increased access to health
care amongst these populations. The most common
presentation is that of a female with an erosive
arthritis and papulo-nodular rash. A retrospective
medical record review conducted at the Mayo clinic
revealed skin and joint involvement in all patients.
Majority of patients had skin or mucosal papulo-
nodular lesions followed by joint involvement,
fatigue and unintentional weight loss. All patients
had skin and joint involvement. The most commonly
J Ayub Med Coll Abbottabad 2023;35(2)
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affected areas of skin included hands, arms and back.
The majority of the patients reported joint pains and
most had clinically detectable joint effusion or
synovitis. The hand joints including the DIPs, PIPs,
MCPs and wrist were most commonly affected
followed by the knees.6 These findings are consistent
with other cases reported worldwide.7–10
Occasionally, patients may have popular xanthomas,
which have distinct histopathological findings.9,10
Multicentric Reticulohistiocytosis can
present with visceral involvement and overlap with
other autoimmune conditions. Most commonly
affected systems include the heart and lungs. When
the pulmonary system is involved, the patient may
present with pleural effusion, hilar lymphadenopathy
and pulmonary fibrosis. Cardiac involvement may
manifest as myocarditis and pericardial effusion.11
Muscular involvement in the form of proximal
muscle weakness and myalgia has also been
documented.12 In up to a third of patients, MRH may
co-exist with other autoimmune conditions such as
rheumatoid arthritis (RA), Systemic Lupus
Erythematosus (SLE), Sjogren's syndrome,
scleroderma or hypothyroidism.13–15Rheumatoid
Factor, ANA and anti-CCP are usually negative but
in case of overlapping autoimmune diseases
antibodies may be positive.9 Erythrocyte
Sedimentation Rate (ESR) and C-Reactive Protein
(CRP) maybe elevated. Workup should also include
age and gender relevant malignancy screen. Reported
associated malignancies affect various systems and
organs including, sarcoma, lung, larynx, breast,
cervix, colon, mesothelioma, haematological
malignancies and others.16
Multicentric Reticulohistiocytosis may be
easily confused with other inflammatory arthritis
such as rheumatoid or psoriatic arthritis. Other
important differentials that need to be ruled out
include dermatomyositis, fibroblastic rheumatism,
gouty arthritis etc. A good knowledge of its clinical
features in addition to radiographic and
histopathological investigation may aid in early
diagnosis and differentiation from other diseases with
similar presentations. Imaging may aid in diagnosis
by identifying erosions, soft tissue swellings,
contractures and deformities. Skin biopsy is the most
useful and specific test to diagnose MRH. There is no
biomarker that may be used specifically to diagnose
this condition. Biopsy of the skin shows a histiocytes
predominant infiltrate with “ground glass” or
“foamy” Eosinophilic cytoplasm, multinucleated
giant cells. These cells are positive for Cd-68, CD-
163 and Ki-M1P. The giant cells stain positive for
periodic acid-Schiff. Similar findings may be
demonstrated in the synovial biopsy.17,18
To this day, no treatment consensus or
guidelines exist for the treatment of Multicentric
Reticulohistiocytosis. Case reports have suggested
the use of various drugs including, Non-Steroidal
Anti-Inflammatory Drugs (NSAIDs), glucocorticoids,
bisphosphonates, and conventional synthetic and
biological Disease Modifying Anti-Rheumatic drugs
(DMARDs). NSAIDs may be beneficial in early and
mild diseases. However, in case of aggressive and
deforming disease DMARDs may be initiated as soon
as the diagnosis is made and low dose corticosteroids
should be given as a bridging therapy. The most
effective initial treatment is methotrexate, which may
benefit both skin and joint disease. Other
conventional synthetic DMARDs that maybe tries
include leflunomide, azathioprine and
cyclophosphamide. Biological DMARDs mainly
Tumour Necrosis Factor (TNF) inhibitors have been
tried with variable success.5,7,9–11 Bisphosphonates
may be added in case of poor disease control, in the
presence of osteoporosis or steroid use.6,11,19 Majority
of the cases respond well to the treatment and remit
spontaneously. Thus, the disease carries a good
prognosis in terms of survival. In case of concomitant
malignancy, treatment of malignancy may lead to
resolution of MRH.12,19
CONCLUSION
MRH is a rare disease of unknown aetiology. We
presented a case of a Pakistani man with MRH who
presented with typical maculopapular rash and
inflammatory arthritis. Initiation of timely treatment
with DMARDs in the patient resulted in remission of
disease. Early and prompt diagnosis is the key to
preventing disability. We could not find evidence of
malignancy in our patient but it should be screened
for in all cases of MRH.
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Submitted: March 1, 2021
Revised: August 2, 2022
Accepted: August 12, 2022
Address for Correspondence:
Saira Bano, Department of Rheumatology, Pakistan Institute of Medical Sciences, Islamabad-Pakistan
Cell: +92 335 591 8840
Email: sairabano56326@gmail.com
